Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2-mediated signaling.

Fetched: February 15th, 2019, 5:00am GMT

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Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2-mediated signaling.

Exp Dermatol. 2019 Feb 13;:

Authors: Nguyen MB, Valdes VJ, Cohen I, Pothula V, Zhao D, Zheng D, Ezhkova E

Abstract
Merkel cells are mechanosensory cells involved in tactile discrimination. Merkel cells have been primarily studied in the murine back skin, where they are found in specialized structures called touch domes located around primary hair follicles. Yet, little is known about the morphogenesis of Merkel cells in areas of the skin devoid of hair, such as the glabrous paw skin. Here, we describe Merkel cell formation in the glabrous paw skin during embryogenesis. We first found in the glabrous paw skin that Merkel cells were specified at E15.5, 24 hours later, compared to in the back skin. Additionally, by performing lineage-tracing experiments, we found that unlike in the back skin, SOX9(+) cells do not give rise to Merkel cells in the glabrous paw skin. Finally, we compared the transcriptomes of Merkel cells in the back and the glabrous paw skin and showed that they are similar. Genetic and transcriptome studies showed that the formation of Merkel cells in both regions was controlled by similar regulators. Among them was FGFR2, an upstream factor of MAPK signaling that was reported to have a critical function in Merkel cell formation in the back skin. Here, we showed that FGFR2 is also required for Merkel cell development in the glabrous paw skin. Taken together, our results demonstrate that Merkel cells in the murine back skin and glabrous paw skin are similar, and even though their formation is controlled by a common genetic program, their precursor cells might differ. This article is protected by copyright. All rights reserved.

PMID: 30758073 [PubMed - as supplied by publisher]
Immunotherapy for skin cancer.

Fetched: February 14th, 2019, 5:00am GMT

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Immunotherapy for skin cancer.

Int Immunol. 2019 Feb 08;:

Authors: Paulson KG, Lahman M, Chapuis AG, Brownell I

Abstract
Among all tumor types, skin cancers are profoundly sensitive to immunotherapy. Indeed, the recently reported response rates for anti-PD-1 (anti-programmed-death 1) therapy for cutaneous malignant melanomas (MM), Merkel cell carcinomas, basal cell carcinomas, cutaneous squamous cell carcinomas and Kaposi sarcomas are all above 40%. This unique immunogenicity renders skin cancers as a paradigm for tumor-immune interactions and is driven by high mutational burdens, overexpressed tumor antigens and/or viral antigens. However, despite the clear demonstration of immunologic cure of skin cancer in some patients, most tumors develop either early (primary) or late (adaptive) resistance to immunotherapy. Resistance mechanisms are complex, and include contributions of tumor cell-intrinsic, T cell and microenvironment factors that have been recently further elucidated with the advent of single-cell technologies. This review will focus on the exciting progress with immunotherapy for skin cancers to date, and also our current understanding of the mechanisms of resistance to immunotherapy.

PMID: 30753483 [PubMed - as supplied by publisher]
Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma.

Fetched: February 14th, 2019, 5:00am GMT

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Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma.

Virchows Arch. 2019 Feb 12;:

Authors: Ottaviano M, De Placido S, Ascierto PA

Abstract
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies. The first to be approved in 2011 was the anti-CTLA-4 antibody ipilimumab for the treatment of unresectable or metastatic melanoma. Subsequently, the anti-PD-1s, nivolumab and pembrolizumab, received regulatory approvals for the treatment of melanoma and several other cancers. More recently, three anti-PD-L1 antibodies have received approval: atezolizumab and durvalumab for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) and avelumab for the treatment of locally advanced or metastatic urothelial carcinoma and metastatic Merkel cell carcinoma. This review, starting from the results of melanoma trials, highlights in turn different ICIs and data for different indications in several malignancies are included under each drug class.

PMID: 30747264 [PubMed - as supplied by publisher]
Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

Fetched: February 10th, 2019, 5:00am GMT

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Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

Front Oncol. 2019;9:20

Authors: von der Grün J, Winkelmann R, Meissner M, Wieland U, Silling S, Martin D, Fokas E, Rödel C, Rödel F, Balermpas P

Abstract
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration. Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS). Results: Median age at diagnosis was 74 (range, 42-100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045). Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.

PMID: 30733932 [PubMed]
Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

Fetched: February 8th, 2019, 5:00am GMT

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Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

J Clin Oncol. 2019 Feb 06;:JCO1801896

Authors: Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited.
PATIENTS AND METHODS: In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
RESULTS: Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death.
CONCLUSION: Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

PMID: 30726175 [PubMed - as supplied by publisher]
Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant.

Fetched: February 8th, 2019, 5:00am GMT

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Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant.

Am J Dermatopathol. 2017 06;39(6):489-491

Authors: Aung PP, Rady PL, Nagarajan P, Ivan D, Tetzlaff MT, Curry JL, Tyring SK, Prieto VG, Torres-Cabala CA

PMID: 27655121 [PubMed - indexed for MEDLINE]
Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Fetched: February 7th, 2019, 5:01am GMT

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Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Cancer Immunol Immunother. 2019 Feb 05;:

Authors: D'Angelo SP, Hunger M, Brohl AS, Nghiem P, Bhatia S, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Schlichting M, Hennessy MH, Bharmal M

Abstract
BACKGROUND: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1).
METHODS: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies.
RESULTS: Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6-97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7-37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4-12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018-0.152)] compared with a nonresponse.
CONCLUSIONS: Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance.

PMID: 30721341 [PubMed - as supplied by publisher]
Diagnosis and comprehensive therapy for cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and literature review.

Fetched: February 7th, 2019, 5:01am GMT

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Diagnosis and comprehensive therapy for cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and literature review.

Braz J Otorhinolaryngol. 2018 Nov - Dec;84(6):799-801

Authors: Xiu Q, Wang XJ, Zhu DD, Meng CD

PMID: 27166275 [PubMed - indexed for MEDLINE]
Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells.

Fetched: February 6th, 2019, 5:00am GMT

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Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells.

Oncoimmunology. 2019;8(2):e1546544

Authors: Davis DA, Shrestha P, Aisabor AI, Stream A, Galli V, Pise-Masison CA, Tagawa T, Ziegelbauer JM, Franchini G, Yarchoan R

Abstract
Most chronic viruses evade T-cell and natural killer (NK) immunity through downregulation of immune surface markers. Previously we showed that Pomalidomide (Pom) increases surface expression of major histocompatibility complex class I (MHC-I) in Kaposi sarcoma-associated herpesvirus-infected latent and lytic cells and restores ICAM-1 and B7-2 in latent cells. We explored the ability of Pom to increase immune surface marker expression in cells infected by other chronic viruses, including human T-cell leukemia virus type-1 (HTLV-1), Epstein-Barr virus (EBV), human papilloma virus (HPV), Merkel cell polyoma virus (MCV), and human immunodeficiency virus type-1 (HIV-1). Pom increased MHC-1, ICAM-1, and B7-2/CD86 in immortalized T-cell lines productively infected with HTLV-1 and also significantly increased their susceptibility to NK cell-mediated cytotoxicity. Pom enhancement of MHC-I and ICAM-1 in primary cells infected with HTLV-1 was abrogated by knockout of HTLV-1 orf-1. Pom increased expression of ICAM-1, B7-2 and MHC class I polypeptide related sequence A (MICA) surface expression in the EBV-infected Daudi cells and increased their T-cell activation and susceptibility to NK cells. Moreover, Pom increased expression of certain of these surface markers on Akata, Raji, and EBV lymphoblastic cell lines. The increased expression of immune surface markers in these virus-infected lines was generally associated with a decrease in IRF4 expression. By contrast, Pom treatment of HPV, MCV and HIV-1 infected cells did not increase these immune surface markers. Pom and related drugs may be clinically beneficial for the treatment of HTLV-1 and EBV-induced tumors by rendering infected cells more susceptible to both innate and adaptive host immune responses.

PMID: 30713808 [PubMed]
Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

Fetched: February 3rd, 2019, 5:00am GMT

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Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

Br J Haematol. 2019 Jan 31;:

Authors: Zheng G, Chattopadhyay S, Sud A, Sundquist K, Sundquist J, Försti A, Houlston R, Hemminki A, Hemminki K

Abstract
Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non-Hodgkin lymphoma and melanoma. The concordance between RRs for bi-directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi-directional risks with skin cancers and other immune-related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

PMID: 30706458 [PubMed - as supplied by publisher]
Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands.

Fetched: February 2nd, 2019, 5:00am GMT

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Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands.

J Am Acad Dermatol. 2019 Jan 28;:

Authors: Uitentuis SE, Louwman MWJ, van Akkooi ACJ, Bekkenk M

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and potentially lethal skin-cancer. MCC is known for its potential rapid growth and its propensity to metastasise.
OBJECTIVE: To describe the incidence, treatment and survival of MCC in a population-based setting.
METHODS: All MCC's diagnosed in the Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, therapy and vital status were obtained. Cox' proportional hazards were computed and relative survival analyses were performed.
RESULTS: Our cohort included 1977 patients with MCC. Incidence increased from 0.17/100,000 personyears in 1993 to 0.59/100,000 in 2016. The mean age at diagnosis was 75.5. Most MCC's (59.8%), were treated with surgery alone. Relative five-year survival was low (63.0%) and did not improve. Mortality was higher among males (HR: 1.24, 95%CI: 1.11-1.39), higher age (HR 1.07, 95%CI: 1.06-1.07) and nodal (HR1.26, 95%CI: 1.08-1.48) and distant spread of disease (HR2.44, 95%CI: 1.99-2.99).
LIMITATIONS: We lacked data on cause of death, comorbidity and pathological margins, which may have led to misinterpretation of the data.
CONCLUSION: This study shows continuously increasing incidence rates of MCC in the Netherlands. Survival after MCC diagnosis remained low. Our results emphasise the need for implementation of new therapies.

PMID: 30703452 [PubMed - as supplied by publisher]
Decreased 5-hydroxymethylcytosine immunoreactivity in primary Merkel cell carcinomas is a strong predictor for disease-specific death.

Fetched: February 2nd, 2019, 5:00am GMT

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Decreased 5-hydroxymethylcytosine immunoreactivity in primary Merkel cell carcinomas is a strong predictor for disease-specific death.

Br J Dermatol. 2019 Jan 31;:

Authors: Gambichler T, Schmitt K, Rüddel I, Stockfleth E, Becker JC

Abstract
Merkel cell carcinoma (MCC) is an infrequent malignant skin tumour with epithelial and neuroendocrine differentiation. Though it is a highly aggressive malignancy, the distinct molecular pathogenesis of MCC is not yet fully understood. Apart from DNA methylation, histone modification, and microRNA-mediated and long non-coding RNA-mediated regulation, hydroxymethylation may also play an important role in cancer development. Loss of 5-hydoxymethylcytosine (5-hmc) has been reported in a variety of cancers, including skin malignancies such as melanoma. This article is protected by copyright. All rights reserved.

PMID: 30703276 [PubMed - as supplied by publisher]
[Merkel cell carcinoma].

Fetched: February 2nd, 2019, 5:00am GMT

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[Merkel cell carcinoma].

Hautarzt. 2019 Jan 30;:

Authors: Drusio C, Becker JC, Schadendorf D, Ugurel S

Abstract
Merkel cell carcinoma is a rare, highly aggressive skin tumor with neuroendocrine features found in older people. The pathogenesis is associated with immunosuppression, chronic UV light exposure and the Merkel cell polyomavirus. Clinically, Merkel cell carcinoma presents as a solitary, cutaneous or subcutaneous, red to bluish node. Due to early lymphogenic metastasis, locoregional metastases are already present in approximately 30% of cases at the time of diagnosis. The frequent local recurrences as well as the regional and distant metastases usually appear within the first 2-3 years after the initial diagnosis. The first treatment after diagnosis consists of complete surgical removal of the primary tumor with wide safety margins as well as a sentinel lymph node biopsy. Subsequently, adjuvant irradiation of the primary site should be performed. By additional radiotherapy of the regional lymph node stations, the rate of locoregional recurrence can be reduced. For systemic therapy of advanced Merkel cell carcinoma checkpoint inhibitors targeted against the PD-1/PD-L1 axis have proven to be highly and durably effective. In contrast the formerly frequently used chemotherapy shows moderate to good response rates but they are as a rule very short-lived.

PMID: 30701288 [PubMed - as supplied by publisher]
Incurable, progressive Merkel cell carcinoma: A single-institution study of 54 cases.

Fetched: February 1st, 2019, 5:00am GMT

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Incurable, progressive Merkel cell carcinoma: A single-institution study of 54 cases.

Clin Otolaryngol. 2018 04;43(2):678-682

Authors: Fochtmann-Frana A, Haymerle G, Loewe R, Grasl MC, Pammer J, Rath T, Perisanidis C, Erovic BM

PMID: 28981217 [PubMed - indexed for MEDLINE]
New perspectives in Merkel cell carcinoma.

Fetched: January 31st, 2019, 5:01am GMT

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New perspectives in Merkel cell carcinoma.

Curr Opin Oncol. 2019 Jan 28;:

Authors: Del Marmol V, Lebbé C

Abstract
PURPOSE OF REVIEW: Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements.
RECENT FINDINGS: Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy - in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade - is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development.
SUMMARY: New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapies should continue to be investigated.

PMID: 30694842 [PubMed - as supplied by publisher]
Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.

Fetched: January 30th, 2019, 5:00am GMT

Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.

PLoS Pathog. 2019 Jan 28;15(1):e1007543

Authors: Dye KN, Welcker M, Clurman BE, Roman A, Galloway DA

Abstract
Merkel cell polyomavirus (MCPyV) accounts for 80% of all Merkel cell carcinoma (MCC) cases through expression of two viral oncoproteins: the truncated large T antigen (LT-t) and small T antigen (ST). MCPyV ST is thought to be the main driver of cellular transformation and has also been shown to increase LT protein levels through the activity of its Large-T Stabilization Domain (LSD). The ST LSD was reported to bind and sequester several ubiquitin ligases, including Fbw7 and β-TrCP, and thereby stabilize LT-t and several other Fbw7 targets including c-Myc and cyclin E. Therefore, the ST LSD is thought to contribute to transformation by promoting the accumulation of these oncoproteins. Targets of Fbw7 and β-TrCP contain well-defined, conserved, phospho-degrons. However, as neither MCPyV LT, LT-t nor ST contain the canonical Fbw7 phospho-degron, we sought to further investigate the proposed model of ST stabilization of LT-t and transformation. In this study, we provide several lines of evidence that fail to support a specific interaction between MCPyV T antigens and Fbw7 or β-TrCP by co-immunoprecipitation or functional consequence. Although MCPyV ST does indeed increase LT protein levels through its Large-T Stabilization domain (LSD), this is accomplished independently of Fbw7. Therefore, our study indicates a need for further investigation into the role and mechanism(s) of MCPyV T antigens in viral replication, latency, transformation, and tumorigenesis.

PMID: 30689667 [PubMed - as supplied by publisher]
Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

Fetched: January 28th, 2019, 5:00am GMT

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Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

Eur J Cancer. 2019 Jan 22;109:21-27

Authors: Rogado J, Sánchez-Torres JM, Romero-Laorden N, Ballesteros AI, Pacheco-Barcia V, Ramos-Leví A, Arranz R, Lorenzo A, Gullón P, Donnay O, Adrados M, Costas P, Aspa J, Alfranca A, Mondéjar R, Colomer R

Abstract
BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy.
PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS.
RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences.
CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

PMID: 30682533 [PubMed - as supplied by publisher]
Avelumab Immunotherapy: Management of Adverse Events Associated With New Treatment for Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

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Avelumab Immunotherapy: Management of Adverse Events Associated With New Treatment for Merkel Cell Carcinoma.

Clin J Oncol Nurs. 2019 Feb 01;23(1):E1-E9

Authors: Ugolini H, Bryan J, Hennessy M, Kaufman HL, D'Angelo S

Abstract
BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is a rare skin cancer with poor prognosis. Avelumab is the first approved treatment option for patients with mMCC. Immune checkpoint inhibitors, such as avelumab, are associated with unique toxicities that can be effectively addressed with prompt recognition and appropriate management.
OBJECTIVES: This article discusses the use of avelumab for the treatment of mMCC and management of associated toxicities.
METHODS: Literature on mMCC disease state and clinical trial data for avelumab were reviewed.
FINDINGS: Avelumab has been investigated in patients with mMCC either following disease progression after one or more prior lines of chemotherapy or no prior systemic therapy. These patients experience clinically meaningful benefit. About 70% of patients receiving avelumab experience treatment-related adverse events. Given the limited benefit of chemotherapy, managing symptoms related to avelumab is key to administering this effective treatment to patients with mMCC.

PMID: 30682006 [PubMed - in process]
Cost Effectiveness of Avelumab for Metastatic Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

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Cost Effectiveness of Avelumab for Metastatic Merkel Cell Carcinoma.

Pharmacoecon Open. 2019 Jan 24;:

Authors: Bullement A, Nathan P, Willis A, Amin A, Lilley C, Stapelkamp C, Hatswell A, Pescott C, Bharmal M

Abstract
BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is a rare and aggressive skin cancer. Until recently, there were no licensed treatment options for patients with mMCC, and prognosis was poor. A cost-effectiveness analysis was conducted for avelumab, a newly available treatment option for mMCC, versus standard care (SC), from a UK National Health Service perspective.
METHODS: A partitioned survival model was developed to assess the lifetime costs and effects of avelumab versus SC. Data from the JAVELIN Merkel 200 trial (NCT02155647) were used to inform estimates of quality-adjusted life-years (QALYs). Unit costs and associated frequencies of use were informed by published literature and clinical expert opinion. Results were presented as incremental cost-effectiveness ratios (ICERs, i.e. the cost per QALY gained) for treatment-experienced (TE) and treatment-naïve (TN) patients. Uncertainty was explored through a range of sensitivity analyses.
RESULTS: Discounting costs and QALYs at 3.5% per annum, avelumab was associated with ICERs of £35,274 (TE)/£39,178 (TN) per QALY gained. Probabilistic sensitivity analysis results demonstrated that avelumab was associated with an 88.3% (TE)/69.3% (TN) probability of being cost effective at a willingness-to-pay threshold for end-of-life treatments of £50,000 per QALY gained. Results were most sensitive to alternative survival extrapolations and dosing assumptions.
CONCLUSIONS: The analysis results suggest that avelumab is likely to be a cost-effective treatment option for UK mMCC patients. The results for TN patients are subject to some uncertainty, and a confirmatory analysis will be conducted with more mature data.

PMID: 30680676 [PubMed - as supplied by publisher]
Activation of Protein Kinase C ε in Merkel Cell Polyomavirus-Induced Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

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Activation of Protein Kinase C ε in Merkel Cell Polyomavirus-Induced Merkel Cell Carcinoma.

JAMA Dermatol. 2017 09 01;153(9):931-932

Authors: Costa A, Mackelfresh J, Gilbert L, Bonner MY, Arbiser JL

PMID: 28564697 [PubMed - indexed for MEDLINE]
Spontaneous Regression of Merkel Cell Carcinoma of the Male Breast with Ongoing Immune Response.

Fetched: January 26th, 2019, 5:00am GMT

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Spontaneous Regression of Merkel Cell Carcinoma of the Male Breast with Ongoing Immune Response.

Cureus. 2018 Nov 14;10(11):e3589

Authors: Nijjar Y, Bigras G, Tai P, Joseph K

Abstract
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor arising predominantly on sun-exposed skin among the elderly. The most common location is the head and neck, followed by the extremities. MCCs are highly aggressive tumors and rarely undergo spontaneous regression. We report a case of MCC which presented as a painless breast lump in an elderly male where the tumor regressed spontaneously after a biopsy.

PMID: 30675444 [PubMed]
Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.

Fetched: January 26th, 2019, 5:00am GMT

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Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.

Oncol Lett. 2019 Feb;17(2):1768-1776

Authors: Müller CSL, Kreie L, Bochen F, Pfuhl T, Smola S, Gräber S, Vogt T, Schick B, Linxweiler M

Abstract
Atypical fibroxanthoma (AFX) is a rare mesenchymal tumor with predominance in older male patients located mainly in chronically UV-exposed skin. Differentiation from clinically more aggressive pleomorphic dermal sarcoma (PDS) is still under debate and immunohistochemical markers are not available yet. An immunohistochemical study, including 41 cases of AFX was conducted to investigate the expression of 3q encoded oncogene SEC62 in AFX and determine the associations with histomorphologic, clinical and viral parameters. Our cohort displayed a mean of 79.9 years at the onset of the disease. In total, 90.2% (37/41) AFXs were located in the head and neck area, whereas, four were located at the extremities (9.7%). Tumor diameter ranged between 0.06 and 40 cm2 with a mean of 5.7 cm2. SEC62 expression was markedly increased in lesional tissue compared with the adjacent healthy squamous epithelium. We found significantly higher expression of SEC62 in cases of AFX with tumor necrosis. Tendency of higher Sec62-IRS-scores were found for tumors with higher Clark levels and a tumor size >5 cm2. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer as well as head and neck squamous cell carcinoma. For the first time, to the best of our knowledge, we suggest a role of 3q oncogene SEC62 in AFX and discuss a potential prognostic relevance in cases of disputable AFX with unfavorable histomorphologic features and may initiate a discussion on Sec62 serving as discriminating marker between AFX and PDS.

PMID: 30675236 [PubMed]
Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results registry-based cohort study.

Fetched: January 26th, 2019, 5:00am GMT

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Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results registry-based cohort study.

J Am Acad Dermatol. 2018 Dec;79(6):1146-1148

Authors: Liu MA, Nguyen J, Driver JA

PMID: 29864470 [PubMed - indexed for MEDLINE]
Cytological diagnosis of a rare case of primary Merkel cell carcinoma of the parotid gland.

Fetched: January 26th, 2019, 5:00am GMT

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Cytological diagnosis of a rare case of primary Merkel cell carcinoma of the parotid gland.

Cytopathology. 2017 12;28(6):552-554

Authors: Bizzarro T, Buda R, Ricci M, Bernardi L

PMID: 29052284 [PubMed - indexed for MEDLINE]
Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant.

Fetched: January 25th, 2019, 5:00am GMT

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Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant.

JAMA Dermatol. 2019 Jan 23;:

Authors: Gao Y, Twigg AR, Hirose R, Roll GR, Nowacki AS, Maytin EV, Vidimos AT, Rajalingam R, Arron ST

Abstract
Importance: Risk factors for the development of skin cancer after solid-organ transplant can inform clinical care, but data on these risk factors are limited.
Objective: To study the association between HLA antigen mismatch and skin cancer incidence after solid-organ transplant.
Design, Setting, and Participants: This retrospective cohort study is a secondary analysis of the multicenter Transplant Skin Cancer Network study of 10 649 adults who underwent a primary solid-organ transplant between January 1, 2003, and December 31, 2003, or between January 1, 2008, and December 31, 2008. These participants were identified through the Scientific Registry of Transplant Recipients standard analysis files, which contain data collected mostly by the Organ Procurement and Transplantation Network. Participants were matched to skin cancer outcomes by medical record review. This study was conducted from August 1, 2016, to July 31, 2017.
Main Outcomes and Measures: The primary outcome was time to diagnosis of posttransplant skin cancer, including squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The HLA antigen mismatch was calculated based on the 2016 Organ Procurement and Transplantation Network guidelines. Risk of skin cancer was analyzed using a multivariate Cox proportional hazards regression model.
Results: In total, 10 649 organ transplant recipients (6776 men [63.6%], with a mean [SD] age of 51 [12] years) contributed 59 923 years of follow-up. For each additional mismatched allele, a 7% to 8% reduction in skin cancer risk was found (adjusted hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P = .01). Subgroup analysis found the protective effect of HLA antigen mismatch to be statistically significant in lung (adjusted HR, 0.70; 95% CI, 0.56-0.87; P = .001) and heart (adjusted HR, 0.75; 95% CI, 0.60-0.93; P = .008) transplant recipients but not for recipients of liver, kidney, or pancreas. The degree of HLA-DR mismatch, but not HLA-A or HLA-B mismatch, was the most statistically significant for skin cancer risk (adjusted HR, 0.85; 95% CI, 0.74-0.97; P = .01).
Conclusions and Relevance: The HLA antigen mismatch appears to be associated with reductions in the risk of skin cancer after solid-organ transplant among heart and lung transplant recipients; this finding suggests that HLA antigen mismatch activates the tumor surveillance mechanisms that protect against skin cancer in transplant recipients and that skin cancer risk may be higher in patients who received a well-matched organ.

PMID: 30673077 [PubMed - as supplied by publisher]
Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma.

Fetched: January 25th, 2019, 5:00am GMT

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Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma.

Clin Transl Radiat Oncol. 2019 Feb;15:42-45

Authors: Linge A, Rauschenberg R, Blum S, Spornraft-Ragaller P, Meier F, Troost EGC

Abstract
This case report presents a HIV-positive 60-year old male with Merkel cell carcinoma of his right forearm and pulmonary sarcoidosis, who, after excisions and irradiations of the primary tumour site and subsequent lymph node metastases developed distant metastases. He received radiotherapy to symptomatic mediastinal lymph node metastases followed by Doxorubicin and, after two cycles, by the PD-1 inhibitor Pembrolizumab due to mixed response. Re-staging showed a para-mediastinal, radiotherapy-induced pneumonitis, which was treated by prednisolone due to clinical symptoms. In September 2017, the patient developed a solitary lymph node metastasis next to the right atrium, for which he received stereotactic radiotherapy. The systemic treatment with Pembrolizumab was replaced by the PD-L1 inhibitor Avelumab and is being continued since. The patient has been in complete remission for one year now and the HIV-infection is well-controlled.

PMID: 30671549 [PubMed]
Merkel cell carcinoma of the thigh: case report and review of the literature.

Fetched: January 24th, 2019, 5:00am GMT

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Merkel cell carcinoma of the thigh: case report and review of the literature.

Onco Targets Ther. 2019;12:535-540

Authors: Jiang W, Xu J, Wang R, Wang T, Shu Y, Liu L

Abstract
Background: Merkel cell carcinoma (MCC) is a kind of cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases, including distant metastases and regional nodal metastases. Clinically, MCC often manifests as obvious single painless hard nodules visible in sun irradiation of diameter <2 cm and not uncommonly >2 cm, with rapid growth and metastases, especially lymph node metastases. Due to the aspecific nature of MCC, it is often confused with other skin cancers. Exploring different treatments of MCC is necessary.
Case presentation: The current study describes the case of an 86-year-old retired man, who presented with a 2.5×2.0×1.2 cm red nodule on the right thigh, which was initially diagnosed as subcutaneous small cell cancer. Upon histological and immunohistochemical analysis, the tumor was consistent with a diagnosis of MCC.
Results: Antiangiogenic therapy combining endostar and apatinib was administered and a partial response achieved after 2.0 months of treatment, and 6.5 months of progression-free survival was achieved. Overall survival was 13.0 months.
Conclusion: We believe that antiangiogenic therapy is an extremely effective treatment for MCC, especially for patients who cannot tolerate chemotherapy and radiotherapy.

PMID: 30666132 [PubMed]
Use of Targeted Therapy in the Treatment of Advanced Cutaneous Cancers.

Fetched: January 24th, 2019, 5:00am GMT

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Use of Targeted Therapy in the Treatment of Advanced Cutaneous Cancers.

JAMA Dermatol. 2017 06 01;153(6):501-502

Authors: Council ML

PMID: 28403377 [PubMed - indexed for MEDLINE]
Tuberculosis following PD-1 blockade for cancer immunotherapy.

Fetched: January 19th, 2019, 5:00am GMT

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Tuberculosis following PD-1 blockade for cancer immunotherapy.

Sci Transl Med. 2019 Jan 16;11(475):

Authors: Barber DL, Sakai S, Kudchadkar RR, Fling SP, Day TA, Vergara JA, Ashkin D, Cheng JH, Lundgren LM, Raabe VN, Kraft CS, Nieva JJ, Cheever MA, Nghiem PT, Sharon E

Abstract
Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models, Mtb-infected PD-1-/- mice mount exaggerated TH1 responses that drive lethal immunopathology. Multiple cases of tuberculosis during PD-1 blockade have been observed in patients with cancer, but in humans little is understood about Mtb-specific immune responses during checkpoint blockade-associated tuberculosis. Here, we report two more cases. We describe a patient who succumbed to disseminated tuberculosis after PD-1 blockade for treatment of nasopharyngeal carcinoma, and we examine Mtb-specific immune responses in a patient with Merkel cell carcinoma who developed checkpoint blockade-associated tuberculosis and was successfully treated for the infection. After anti-PD-1 administration, interferon-γ-producing Mtb-specific CD4 T cells became more prevalent in the blood, and a tuberculoma developed a few months thereafter. Mtb-specific TH17 cells, CD8 T cells, regulatory T cells, and antibody abundance did not change before the appearance of the granuloma. These results are consistent with the murine model data and suggest that boosting TH1 function with PD-1 blockade may increase the risk or severity of tuberculosis in humans.

PMID: 30651320 [PubMed - in process]
Cutaneous Malignancy due to Arsenicosis in Bangladesh: 12-Year Study in Tertiary Level Hospital.

Fetched: January 17th, 2019, 5:01am GMT

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Cutaneous Malignancy due to Arsenicosis in Bangladesh: 12-Year Study in Tertiary Level Hospital.

Biomed Res Int. 2018;2018:4678362

Authors: Choudhury MIM, Shabnam N, Ahsan T, Ahsan SMA, Kabir MS, Khan RM, Miah MA, Uddin MK, Liton MAR

Abstract
Bangladesh is grappling with the largest mass poisoning of a population in the world due to contamination of drinking water with naturally occurring inorganic arsenic. It is estimated that 75 million people of 59 (out of 64) districts are at risk of drinking contaminated water with arsenic above 50μg/L. Long term exposure to arsenic causes cancers, including skin, lung, and bladder. This is a randomized prospective study to see the prevalence of skin cancer from arsenic affected area of Bangladesh, as well as their variation by geographical area, age, gender, location on the body, and socioeconomic conditions, in outpatient department of plastic surgery unit of Bangabandhu Sheikh Mujib Medical University (BSMMU). A total of 960 patients with skin cancers comprised of 528 males and 432 females were selected for the study from January 2004 to December 2015. In this 12-year study, we found squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma to be associated with the ingestion of arsenic contaminated ground water. This is a reflection of a small part of the total national scenario of devastating result of arsenic mediated cancer in terms of skin malignancy. This study will help the future researchers who are contemplating to work on arsenic induced health problem.

PMID: 30643806 [PubMed - in process]
Update on eighth edition American Joint Committee on Cancer classification for Merkel cell carcinoma and histopathological parameters that determine prognosis.

Fetched: January 16th, 2019, 5:00am GMT

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Update on eighth edition American Joint Committee on Cancer classification for Merkel cell carcinoma and histopathological parameters that determine prognosis.

J Clin Pathol. 2019 Jan 13;:

Authors: Trinidad CM, Torres-Cabala CA, Prieto VG, Aung PP

Abstract
Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. The annual incidence of MCC is increasing in the USA. Timely diagnosis and proper staging of this tumour are crucial as MCC has high rates of regional recurrence and lymph node and distant metastasis. In this review, we outline the key differences between the tumor node metastasis (TNM) staging criteria for MCC in the seventh and eighth editions of the AJCC Cancer Staging Manual We also discuss histopathological parameters that are not included in the eighth edition of the manual but have been shown in other studies to predict a worse prognosis in patients with MCC. Correct assessment and reporting of these clinically relevant histopathological parameters is of utmost importance for practising pathologists as management differs according to the stage of the tumour. This review aims to increase awareness of all these parameters, and proper recognition would guide the treating clinicians towards the most appropriate treatment options that can be given to patients.

PMID: 30636696 [PubMed - as supplied by publisher]
Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with SCC in situ and actinic keratosis.

Fetched: January 13th, 2019, 5:01am GMT

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Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with SCC in situ and actinic keratosis.

Transpl Int. 2019 Jan 10;:

Authors: Wang Y, Keinonen A, Koskenmies S, Pitkänen S, Fyhrquist N, Sadeghi M, Mäkisalo H, Söderlund-Venermo M, Hedman K

Abstract
To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV) and Lyon IARC polyomavirus (LIPyV), were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant vs. benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development. This article is protected by copyright. All rights reserved.

PMID: 30632206 [PubMed - as supplied by publisher]
Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.

Fetched: January 13th, 2019, 5:01am GMT

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Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.

Front Med (Lausanne). 2018;5:351

Authors: Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA

Abstract
Immunotherapy for skin malignancies has ushered in a new era for cancer treatments by demonstrating unprecedented durable responses in the setting of metastatic Melanoma. Consequently, checkpoint inhibitors are now the first-line treatment of metastatic melanoma and widely used as adjuvant therapy for stage III disease. With the observation that higher tumor mutational burden correlates with a better response, checkpoint inhibitors are tested in other skin cancer types of known high tumor mutational burden with promising results and recently became the first-ever FDA-approved treatment for metastatic Merkel cell carcinoma. The emerging new standards-of-care will necessitate more precise biomarkers and predictors for treatment response and immune-related adverse events. Measurable immune-related mediators are currently under investigation as factors that promote or block the response to cancer immunotherapy and may provide insights into the underlying immune response to the tumor. Cytokines and chemokines are such mediators and are crucial for facilitating the recruitment and activation of specific subsets of leukocytes within the microenvironment of skin cancers. The exact mechanisms of how these meditators, both immunological and non-immunological, operate in the tumor microenvironment is an area of active research, so to reliable biomarkers of responses to cancer immunotherapy. Here, we will review and summarize the expanding body of literature for immune-related biomarkers pertaining to Melanoma, Basal cell carcinoma, Squamous cell carcinoma, and Merkel cell carcinoma, highlighting clinically relevant checkpoint inhibitor therapy biomarker advancements.

PMID: 30631766 [PubMed]
Low prevalence of Merkel cell polyomavirus in human epithelial thymic tumors.

Fetched: January 12th, 2019, 5:00am GMT

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Low prevalence of Merkel cell polyomavirus in human epithelial thymic tumors.

Thorac Cancer. 2019 Jan 09;:

Authors: Chteinberg E, Klufah F, Rennspiess D, Mannheims MF, Abdul-Hamid MA, Losen M, Keijzers M, De Baets MH, Kurz AK, Zur Hausen A

Abstract
BACKGROUND: The etiology of thymic epithelial tumors is unknown. Murine polyomavirus strain PTA has been shown to induce thymomas in mice. Recently, using diverse molecular techniques, we reported the presence of human polyomavirus 7 (HPyV7) in thymic epithelial tumors. In the present study, we investigated the prevalence of Merkel cell polyomavirus (MCPyV) in thymic epithelial tumors.
METHODS: Thirty-six thymomas were screened for MCPyV by PCR and subsequently tested by DNA and RNA in situ hybridization and immunohistochemistry. Twenty-six thymomas were diagnosed with myasthenia gravis (MG).
RESULTS: MCPyV DNA was detected by PCR in 7 (19.4%) of the 36 thymic epithelial tumors and in six of these, the presence of MCPyV was confirmed by fluorescence situ hybridization. Of these, 3 (28.6%) revealed weak MCPyV LT-antigen protein expression. In addition, one of the MCPyV positive thymomas tested positive for MCPyV LT RNA with RNAscope. Of interest, two out of the three thymomas that previously tested positive for MCPyV by immunohistochemistry also tested positive for HPyV7. One of the 11 MG-negative and 2 of the 25 MG-positive were positive for MCPyV.
CONCLUSIONS: MCPyV DNA and MCPyV protein expression can be detected in human epithelial thymoma; however, to a far lesser extent than HPyV7. Our data strongly indicate that because of its infrequent detection and weak expression, MCPyV is unlikely to play an important role in the etiopathogenesis of human thymomas.

PMID: 30628176 [PubMed - as supplied by publisher]
Infectious Entry of Merkel Cell Polyomavirus.

Fetched: January 12th, 2019, 5:00am GMT

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Infectious Entry of Merkel Cell Polyomavirus.

J Virol. 2019 Jan 09;:

Authors: Becker M, Dominguez M, Greune L, Soria-Martinez L, Pfleiderer MM, Schowalter R, Buck CB, Blaum BS, Schmidt MA, Schelhaas M

Abstract
Merkel Cell Polyomavirus (MCPyV) is a small, non-enveloped tumor virus associated with an aggressive form of skin cancer, the Merkel cell carcinoma (MCC). MCPyV infections are highly prevalent in the human population with MCPyV virions being continuously shed from human skin. However, the precise host cell tropism(s) of MCPyV remains unclear: MCPyV is able to replicate within a subset of dermal fibroblasts, but MCPyV DNA has also been detected in a variety of other tissues. However, MCPyV appears different from other polyomaviruses as it requires sulfated polysaccharides such as heparan sulfates and/or chondroitin sulfates for initial attachment. Like other polyomaviruses, MCPyV engages sialic acid as a (co-)receptor. To explore the infectious entry process of MCPyV, we analyzed the cell biological determinants of MCPyV entry into A549 cells, a highly transducible lung carcinoma cell line, in comparison to well-studied simian virus 40 and a number of other viruses. Our results indicate that MCPyV enters cells via caveolar/lipid raft-mediated endocytosis but not macropinocytosis, clathrin-mediated endocytosis or glycosphingolipid-enriched carriers. The viruses internalized in small endocytic pits that led the virus to endosomes and from there to the endoplasmic reticulum (ER). Similar to other polyomaviruses, trafficking required microtubular transport, acidification of endosomes, and a functional redox environment. To our surprise, the virus was found to acquire a membrane envelope within endosomes, a phenomenon not reported for other viruses. Only minor amounts of viruses reached the ER, while the majority was retained in endosomal compartments suggesting that endosome-to-ER trafficking is a bottleneck during infectious entry.IMPORTANCE MCPyV is the first polyomavirus directly implicated in the development of an aggressive human cancer, the Merkel Cell Carcinoma (MCC). Although MCPyV is constantly shed from healthy skin, MCC incidence increases among aging and immunocompromised individuals. To date, the events connecting initial MCPyV infection and subsequent transformation still remain elusive. MCPyV differs from other known polyomaviruses concerning its cell tropism, entry receptor requirements, and infection kinetics. In this study, we examined the cellular requirements for endocytic entry as well as the subcellular localization of incoming virus particles. A thorough understanding of the determinants of the infectious entry pathway and the specific biological niche will benefit prevention of virus-derived cancers such as MCC.

PMID: 30626687 [PubMed - as supplied by publisher]
Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma.

Fetched: January 12th, 2019, 5:00am GMT

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Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma.

Clin Chem. 2019 Jan 09;:

Authors: Riethdorf S, Hildebrandt L, Heinzerling L, Heitzer E, Fischer N, Bergmann S, Mauermann O, Waldispühl-Geigl J, Coith C, Schön G, Peine S, Schuler G, Speicher MR, Moll I, Pantel K

Abstract
BACKGROUND: Merkel cell carcinoma (MCC)8 is a rare, aggressive skin cancer with increasing incidence and high mortality rates. MCC has recently become the subject of immune checkpoint therapy, but reliable biomarkers for estimating prognosis, risk stratification, and prediction of response are missing.
METHODS: Circulating tumor cells (CTCs) were detected in peripheral blood from patients with MCC by use of the CellSearch® system. Moreover, CTCs of selected cases were characterized for Merkel cell polyomavirus (MCPyV), chromosomal aberrations, and programed death ligand 1 (PD-L1) production.
RESULTS: Fifty-one patients were tested at first blood draw (baseline), and 16 patients had 2 or 3 consecutive measurements to detect CTCs. At baseline, ≥1 CTC (range, 1-790), >1, or ≥5 CTCs/7.5 mL were detected in 21 (41%), 17 (33%), and 6 (12%) patients, respectively. After a median follow-up of 21.1 months for 50 patients, detection of CTCs correlated with overall survival (≥1, P = 0.030; >1, P < 0.020; and ≥5 CTCs/7.5 mL, P < 0.0001). In multivariate Cox regression analysis, the detection of ≥5 CTCs/7.5 mL adjusted to age and sex compared to that of <5 was associated with a reduced overall survival (P = 0.001, hazard ratio = 17.8; 95% CI, 4.0-93.0). MCPyV DNA and genomic aberrations frequently found in MCC tissues could also be detected in single CTCs. Analyzed CTCs were PD-L1 negative or only weakly positive.
CONCLUSIONS: The presence of CTCs is a prognostic factor of impaired clinical outcome, with the potential to monitor the progression of the disease in real time. Molecular characterization of CTCs might provide new insights into the biology of MCC.

PMID: 30626636 [PubMed - as supplied by publisher]
Cutaneous metastases of pancreatic neuroendocrine carcinoma.

Fetched: January 11th, 2019, 5:00am GMT

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Cutaneous metastases of pancreatic neuroendocrine carcinoma.

G Ital Dermatol Venereol. 2018 Oct;153(5):722-724

Authors: Laschinger ME, Naga L, Gaspari AA

Abstract
Neuroendocrine carcinomas with distant metastases are rarely reported in the literature, with cutaneous metastases being among the most infrequently reported sites. The importance of distinguishing metastatic neuroendocrine carcinoma (NEC) from primary neuroendocrine carcinoma in the skin, or Merkel cell carcinoma (MCC), has been stressed in the literature, with CK20 positivity traditionally being reported as the key diagnostic feature of MCC. Our case not only serves as one of the few reported cases of cutaneous metastases of a visceral NEC, but also serves to caution providers as to the use of CK20 positivity as an absolute diagnostic feature. We present a case of a 67-year-old female with widespread cutaneous metastases of a pancreatic NEC. Immunohistochemical staining revealed CK20 positivity, despite visceral origin of the primary tumor. This case serves to highlight not only a rare presentation of cutaneous metastases of a pancreatic neuroendocrine carcinoma, which has yet to be reported in the literature, but also serves as the only report of a pancreatic NEC with CK20 positivity, providing evidence for cautionary use of CK20 staining for diagnostic purposes, particularly for visceral NECs which have been under-represented in the literature.

PMID: 30246953 [PubMed - indexed for MEDLINE]
The first observation of the association of Merkel cell polyomavirus and Merkel cell carcinoma in Brazil.

Fetched: January 10th, 2019, 5:00am GMT

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The first observation of the association of Merkel cell polyomavirus and Merkel cell carcinoma in Brazil.

Int J Dermatol. 2019 Jan 08;:

Authors: Neto CF, Oliveira WRP, Costa PVA, Cardoso MK, Barreto PG, Romano CM, Urbano PR

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive primary cutaneous carcinoma with high mortality rates. The present study intends to delineate the epidemiological profile of patients with MCC seen at the Clinics Hospital of the Medical School at the University of São Paulo, Brazil, and its association with Merkel cell polyomavirus (MCPyV).
METHODS: This is a retrospective study. A search was performed in the hospital's medical index for all cases of MCC from January 1994 to December 2012. Among patients with MCC, the available tumoral skin specimens were analyzed with two different techniques of polymerase chain reaction (PCR) (conventional and real-time) for detection of MCPyV DNA. Additionally, paraffin-embedded samples of patients with non-MCC skin cancers were also analyzed. Analyses suitable for categorical data (i.e., x² of Fisher) were used to compare the proportion of patients in each group.
RESULTS: Nineteen patients with MCC and 20 patients with non-MCC skin cancers entered the study. All MCC samples available (13) tested positive for the presence of MCPyV DNA; however, in the non-MCC skin cancer samples, the MCPyV DNA was detected in 4 of 20 samples (20%). MCPyV DNA detection rate was higher in patients with MCC than in the other group, and its analysis was statistically significant (P < 0.01).
CONCLUSIONS: This study demonstrates the association of MCPyV in Brazilian patients with MCC. However, further studies are necessary to determine the exact involvement of MCPyV in MCC pathogenesis and to define the significance of viral DNA detection in non-MCC skin cancers.

PMID: 30620056 [PubMed - as supplied by publisher]
Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions.

Fetched: January 10th, 2019, 5:00am GMT

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Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions.

J Cancer Res Clin Oncol. 2019 Jan 07;:

Authors: Gallo M, Guarnotta V, De Cicco F, Rubino M, Faggiano A, Colao A, NIKE Group

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC.
METHODS: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic.
RESULTS: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response?
CONCLUSION: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited.

PMID: 30617553 [PubMed - as supplied by publisher]

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Small Cell Lung Cancer Therapeutics Market by Size | Growth | Analysis | Trends and Forecasts to 2018-2026 - Crypto News Today

Posted: February 16th, 2019, 3:51am GMT

Small Cell Lung Cancer Therapeutics Market by Size | Growth | Analysis | Trends and Forecasts to 2018-2026 Crypto News Today
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ASCO GU 2019: Biologic Basis for Sequencing Novel Treatments for Metastatic Prostate Cancer - UroToday

Posted: February 15th, 2019, 6:34pm GMT

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Reviewing OncoSec Medical Incorporated (ONCS)'s and Aquestive Therapeutics Inc. (NASDAQ:AQST)'s results - EN Digest

Posted: February 15th, 2019, 4:26pm GMT

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Posted: February 15th, 2019, 12:50pm GMT

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Irrfan Khan Returns To Mumbai After Cancer Treatment In London - Woman's Era

Posted: February 14th, 2019, 9:29am GMT

Irrfan Khan Returns To Mumbai After Cancer Treatment In London Woman's Era
In March 2018, the news that Irfan Khan is suffering from a rare form of cancer took the town by storm. Soon, he left for London to undergo treatment for the ...
Ipsen Delivers Strong 2018 Results and Expects Continued Sales and Profit Growth in 2019 - Business Wire

Posted: February 14th, 2019, 4:00am GMT

Ipsen Delivers Strong 2018 Results and Expects Continued Sales and Profit Growth in 2019 Business Wire
PARIS--(BUSINESS WIRE)--Regulatory News: “Net change in other operating assets and liabilities”. Tweet this. Ipsen (Euronext: IPN; ADR: IPSEY), a global ...
Irrfan Khan Back in India After Cancer Treatment in London, Soon to Begin Shooting For Hindi Medium 2 - India.com News

Posted: February 14th, 2019, 2:43am GMT

Irrfan Khan Back in India After Cancer Treatment in London, Soon to Begin Shooting For Hindi Medium 2 India.com News
Bollywood fans have been eagerly waiting for the return of its stellar actor Irrfan Khan ever since he has been undergoing treatment for Neuroendocrine tumor in ...
Reviewing ASLAN Pharmaceuticals Limited (ASLN)'s and Aquestive Therapeutics Inc. (NASDAQ:AQST)'s results - The Moveefy

Posted: February 14th, 2019, 12:18am GMT

Reviewing ASLAN Pharmaceuticals Limited (ASLN)'s and Aquestive Therapeutics Inc. (NASDAQ:AQST)'s results The Moveefy
ASLAN Pharmaceuticals Limited (NASDAQ:ASLN) and Aquestive Therapeutics Inc. (NASDAQ:AQST) compete with each other in the Biotechnology sector.
Survivor Story: Heriberto Borges - Pancreatic Cancer News & Stories

Posted: February 13th, 2019, 7:28pm GMT

Survivor Story: Heriberto Borges Pancreatic Cancer News & Stories
Read the story of a stage IV pancreatic cancer survivor.
Marker Therapeutics Inc. (MRKR) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) Contrasting side by side - The FinExaminer

Posted: February 13th, 2019, 4:44pm GMT

Marker Therapeutics Inc. (MRKR) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) Contrasting side by side The FinExaminer
Marker Therapeutics Inc. (NASDAQ:MRKR) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) have been rivals in the Biotechnology for quite some time.
Filling Critical Gaps: Where Grants for Cancer Research Are Going so Far This Year - Inside Philanthropy

Posted: February 13th, 2019, 4:25pm GMT

Filling Critical Gaps: Where Grants for Cancer Research Are Going so Far This Year Inside Philanthropy
We've tracked nearly $80 million in new commitments for cancer research so far this year. With funders keen to leverage limited resources for maximum impact, ...
Cancer survivor Irrfan to start shooting 'Hindi Medium-2' next week - NewsBytes

Posted: February 13th, 2019, 4:19am GMT

Cancer survivor Irrfan to start shooting 'Hindi Medium-2' next week NewsBytes
It's been almost a year since Irrfan Khan was diagnosed with high-grade Neuroendocrine tumor, a piece of news that had left his fans aghast. While everyone ...
ImmunoCellular Therapeutics Ltd. (IMUC)'s Financial Results Comparing With Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) - The FinReviewer

Posted: February 13th, 2019, 12:45am GMT

ImmunoCellular Therapeutics Ltd. (IMUC)'s Financial Results Comparing With Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) The FinReviewer
We are comparing ImmunoCellular Therapeutics Ltd. (OTCMKTS:IMUC) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) on their risk, analyst ...
Cellectar Biosciences Inc. (CLRB)'s Financial Results Comparing With Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) - The Hi New Ulm

Posted: February 12th, 2019, 6:02pm GMT

Cellectar Biosciences Inc. (CLRB)'s Financial Results Comparing With Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) The Hi New Ulm
Cellectar Biosciences Inc. (NASDAQ:CLRB) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) compete with each other in the Biotechnology sector. We will ...
Embolization Coils Market To Boom In Near Future By 2025 Terumo Medical Corporation, Medtronic, Boston Scientific Corporation or its affiliates, Stryker, DePuy Synthes, Cook, EndoShape, Inc., Balt USA LLC, Penumbra - openPR

Posted: February 12th, 2019, 2:07pm GMT

Embolization Coils Market To Boom In Near Future By 2025 Terumo Medical Corporation, Medtronic, Boston Scientific Corporation or its affiliates, Stryker, DePuy Synthes, Cook, EndoShape, Inc., Balt USA LLC, Penumbra openPR
According to a new market research study titled Embolization Coils market - global analysis and forecasts by type, application and end user, the global ...
Global Neuroendocrine Tumor Treatment Market Widespread Research and Fundamental study to 2026 - openPR

Posted: February 12th, 2019, 12:28pm GMT

Global Neuroendocrine Tumor Treatment Market Widespread Research and Fundamental study to 2026 openPR
Neuroendocrine tumors (NETs) result from the abnormal growth of neoplasms that originate from cells of the various endocrine glands and nervous systems.
FDA Accepts sBLA and Grants Priority Review for BAVENCIO® (avelumab) Plus INLYTA® (axitinib) for the Treatment of Advanced Renal Cell Carcinoma | Antibodies | News Channels - PipelineReview.com

Posted: February 12th, 2019, 8:04am GMT

FDA Accepts sBLA and Grants Priority Review for BAVENCIO® (avelumab) Plus INLYTA® (axitinib) for the Treatment of Advanced Renal Cell Carcinoma | Antibodies | News Channels PipelineReview.com
FDA Accepts sBLA and Grants Priority Review for BAVENCIO® (avelumab) Plus INLYTA® (axitinib) for the Treatment of Advanced Renal Cell Carcinoma.
Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. - UroToday

Posted: February 12th, 2019, 6:00am GMT

Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. UroToday
Purpose The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern ...
FDA Accepts sBLA and Grants Priority Review for BAVENCIO® (avelumab) Plus INLYTA® (axitinib) for the Treatment of Advanced Renal Cell Carcinoma - PRNewswire

Posted: February 11th, 2019, 8:44pm GMT

FDA Accepts sBLA and Grants Priority Review for BAVENCIO® (avelumab) Plus INLYTA® (axitinib) for the Treatment of Advanced Renal Cell Carcinoma PRNewswire
ROCKLAND, Massachusetts and NEW YORK, Feb. 11, 2019 /PRNewswire/ -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, ...
Crinetics Pharmaceuticals Inc. (CRNX)'s Financial Results Comparing With Atara Biotherapeutics Inc. (NASDAQ:ATRA) - The FinHeadLines

Posted: February 11th, 2019, 6:29pm GMT

Crinetics Pharmaceuticals Inc. (CRNX)'s Financial Results Comparing With Atara Biotherapeutics Inc. (NASDAQ:ATRA) The FinHeadLines
Since Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) and Atara Biotherapeutics Inc. (NASDAQ:ATRA) are part of the Biotechnology industry, they are ...
New model sheds light on how small cell lung cancer is initiated - News-Medical.net

Posted: February 11th, 2019, 5:22pm GMT

New model sheds light on how small cell lung cancer is initiated News-Medical.net
Scientists from Weill Cornell Medicine have developed a stem-cell-based model of small cell lung cancer that will help them understand how the disease is ...
TYME Reports Third Quarter Fiscal 2019 Financial and Operating Results - Nasdaq

Posted: February 11th, 2019, 9:30am GMT

TYME Reports Third Quarter Fiscal 2019 Financial and Operating Results Nasdaq
TYME's novel metabolic-based investigational cancer therapy, SM-88, demonstrated encouraging results and a well-tolerated safety profile in a preliminary ...
Contrasting of Aquestive Therapeutics Inc. (AQST) and Cue Biopharma Inc. (NASDAQ:CUE) - D Minute

Posted: February 11th, 2019, 8:29am GMT

Contrasting of Aquestive Therapeutics Inc. (AQST) and Cue Biopharma Inc. (NASDAQ:CUE) D Minute
Aquestive Therapeutics Inc. (NASDAQ:AQST) and Cue Biopharma Inc. (NASDAQ:CUE) compete against each other in the Biotechnology sector. We will contrast ...
Sunday Salute: Ashley Linden dealt with cancer by helping others - The Fayetteville Observer

Posted: February 9th, 2019, 4:01pm GMT

Sunday Salute: Ashley Linden dealt with cancer by helping others The Fayetteville Observer
RAEFORD — Ashley Linden could find hope anywhere. Even in a simple rock.By the time she died Jan. 20 at age 36, she had spread that hope — and those ...
Goop: What a Mess - Clinical Oncology News

Posted: February 9th, 2019, 3:06am GMT

Goop: What a Mess Clinical Oncology News
I'm sure by now you have heard of Goop, Gwyneth Paltrow's multimillion-dollar modern wellness and lifestyle venture launched in 2008. And I'm sure you are ...
CTCA expands Neuroendocrine Tumor Clinical Program with Innovative Therapy for Rare Disease - MDJOnline.com

Posted: February 8th, 2019, 9:13pm GMT

CTCA expands Neuroendocrine Tumor Clinical Program with Innovative Therapy for Rare Disease MDJOnline.com
Physicians at Cancer Treatment Centers of America, Atlanta have a new option in the fight against rare neuroendocrine tumors (NETs) with the introduction of an ...
Foundation Medicine gets genomic profiling contract from Veterans Affairs - The Cancer Letter Publications

Posted: February 8th, 2019, 6:37pm GMT

Foundation Medicine gets genomic profiling contract from Veterans Affairs The Cancer Letter Publications
Foundation Medicine Inc. announced a nationwide contract with the U.S. Department of Veterans Affairs National Precision Oncology Program to provide ...
Genprex Inc. (GNPX)'s Financial Results Comparing With Aquestive Therapeutics Inc. (NASDAQ:AQST) – The Financial Examiner - The FinExaminer

Posted: February 8th, 2019, 6:06pm GMT

Genprex Inc. (GNPX)'s Financial Results Comparing With Aquestive Therapeutics Inc. (NASDAQ:AQST) – The Financial Examiner The FinExaminer
Genprex Inc. (NASDAQ:GNPX) and Aquestive Therapeutics Inc. (NASDAQ:AQST), are influenced by contrast since they are both players in the Biotechnology.
Researchers develop human cell-based model to study small cell lung cancer - Science Daily

Posted: February 8th, 2019, 4:15pm GMT

Researchers develop human cell-based model to study small cell lung cancer Science Daily
Researchers have used human embryonic stem cells to create a new model system that allows them to study the initiation and progression of small cell lung ...
Joel Bass Of Southampton Dies February 5 - Southampton - 27east.com

Posted: February 8th, 2019, 3:32pm GMT

Joel Bass Of Southampton Dies February 5 - Southampton 27east.com
Joel Bass, who resided in Southampton for more than 20 years, and in the Hamptons for more than 30 years, died on February 5, 2019, surrounded by his family ...
Global Cancer mTOR Inhibitors Market Size and Analysis by leading Players with its Application and Type by 2024 With Abraxis BioScience, Adimab, Celgene Corporation, Celator Pharmaceuticals, Eli Lilly, Exelixis, GlaxoSmithKline - Honest Version

Posted: February 8th, 2019, 1:31pm GMT

Global Cancer mTOR Inhibitors Market Size and Analysis by leading Players with its Application and Type by 2024 With Abraxis BioScience, Adimab, Celgene Corporation, Celator Pharmaceuticals, Eli Lilly, Exelixis, GlaxoSmithKline Honest Version
The Global Cancer mTOR Inhibitors market report is generated with the combination of steps which uses a nice blend of industry insights, practical solutions, ...
Sunitinib Malate Market 2018: By Product Type, Segmentation, Market Potential, Influential Trends, And The Challenges, And Forecast To 2023 - TOP Tribune

Posted: February 8th, 2019, 12:07pm GMT

Sunitinib Malate Market 2018: By Product Type, Segmentation, Market Potential, Influential Trends, And The Challenges, And Forecast To 2023 TOP Tribune
Sunitinib Malate Market Report analyse current as well as future aspects of the Sunitinib Malate Industry. The Sunitinib Malate Market provides Sunitinib Malate ...
Priority Review Designation in TGCT, BLA Submitted in HER2+ Breast Cancer, and More - OncLive

Posted: February 7th, 2019, 7:11pm GMT

Priority Review Designation in TGCT, BLA Submitted in HER2+ Breast Cancer, and More OncLive
Gina Columbus reports on a priority review designation in tenosynovial giant cell tumor, a biologic license application submitted in HER2-positive breast cancer, ...
Neuroendocrine Tumors Market Current Trends and Future Aspect Analysis 2018-2026 - Honest Version

Posted: February 7th, 2019, 5:42pm GMT

Neuroendocrine Tumors Market Current Trends and Future Aspect Analysis 2018-2026 Honest Version
Tumor that arises from specialized body cells, called neuroendocrine cells, is known as neuroendocrine tumor. Neuroendocrine tumor arises from cells that ...
Cancer-Associated Circular RNAs Catalogued Across Tumor Types - GenomeWeb

Posted: February 7th, 2019, 4:30pm GMT

Cancer-Associated Circular RNAs Catalogued Across Tumor Types GenomeWeb
NEW YORK (GenomeWeb) – A team led by researchers at the University of Michigan has catalogued and started characterizing circular RNAs (circRNAs) found ...
A classical case of Zollinger-Ellison syndrome - Specialty Medical Dialogues

Posted: February 7th, 2019, 10:45am GMT

A classical case of Zollinger-Ellison syndrome Specialty Medical Dialogues
Dr Ali Alshati department of Internal Medicine, Maricopa Integrated Health System, Creighton University, Phoenix, AZ, USA and colleagues have reported a ...
Advanced Accelerator Applications Announces Health Canada Approval for Lutathera™, a Treatment for Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)¹ - GlobeNewswire

Posted: February 7th, 2019, 10:00am GMT

Advanced Accelerator Applications Announces Health Canada Approval for Lutathera™, a Treatment for Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)¹ GlobeNewswire
SAINT-GENIS-POUILLY, France, Feb. 07, 2019 (GLOBE NEWSWIRE) -- Advanced Accelerator Applications S.A. (AAA), a Novartis company and leader in ...
The art of talking about science - Penn: Office of University Communications

Posted: February 7th, 2019, 10:00am GMT

The art of talking about science Penn: Office of University Communications
Paul Offit of Penn Medicine and CHOP offers five tips for better communicating tough scientific topics to the public—and standing up for science in the process.
NETRF announces $2.5 million funding for neuroendocrine cancer research - News-Medical.net

Posted: February 7th, 2019, 5:34am GMT

NETRF announces $2.5 million funding for neuroendocrine cancer research News-Medical.net
The Neuroendocrine Tumor Research Foundation continues its aggressive funding of neuroendocrine cancer research with eight new grants totaling $2.5 ...
Bispecific, Multispecific Antibodies Grapple with Cancer - Genetic Engineering & Biotechnology News

Posted: February 7th, 2019, 5:01am GMT

Bispecific, Multispecific Antibodies Grapple with Cancer Genetic Engineering & Biotechnology News
Cancer immunotherapy has been advancing on several fronts, most strikingly in the direction of checkpoint inhibition and chimeric antigen receptor (CAR) T-cell ...
Bispecific, Multispecific Antibodies Grapple with Cancer - Genetic Engineering & Biotechnology News

Posted: February 7th, 2019, 5:01am GMT

Bispecific, Multispecific Antibodies Grapple with Cancer Genetic Engineering & Biotechnology News
Cancer immunotherapy has been advancing on several fronts, most strikingly in the direction of checkpoint inhibition and chimeric antigen receptor (CAR) T-cell ...
Nuclear medicine revolutionizes cancer treatment in Northeast Florida - FirstCoastNews.com WTLV-WJXX

Posted: February 6th, 2019, 7:41pm GMT

Nuclear medicine revolutionizes cancer treatment in Northeast Florida FirstCoastNews.com WTLV-WJXX
The term “nuclear medicine” is enough to make your ears perk up. It is also revolutionizing cancer treatment in Northeast Florida and beyond. Just ask Mary ...
'Oncogenetics' improves management of rare neuroendocrine tumors - Healio

Posted: February 6th, 2019, 10:02am GMT

'Oncogenetics' improves management of rare neuroendocrine tumors Healio
Adults with paraganglioma or pheochromocytoma who received genetic testing early after diagnosis were more likely to receive better follow-up care and ...
Global Neuroendocrine Tumor Drug Market Status and Capacity 2019 by Foresee PharmaceuticalsLLC, Eisai, ExelixisInc - Market Reports

Posted: February 6th, 2019, 9:25am GMT

Global Neuroendocrine Tumor Drug Market Status and Capacity 2019 by Foresee PharmaceuticalsLLC, Eisai, ExelixisInc Market Reports
Global Neuroendocrine Tumor Drug Market 2019 Summary. The report on global Neuroendocrine Tumor Drug Market studies the market size (value and ...
Crinetics Pharmaceuticals Inc. (CRNX) and Calithera Biosciences Inc. (NASDAQ:CALA) Comparing side by side - The FinExaminer

Posted: February 6th, 2019, 9:17am GMT

Crinetics Pharmaceuticals Inc. (CRNX) and Calithera Biosciences Inc. (NASDAQ:CALA) Comparing side by side The FinExaminer
Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) and Calithera Biosciences Inc. (NASDAQ:CALA) compete against each other in the Biotechnology sector.
Camurus - Full Year Report 2018 - Markets Insider

Posted: February 6th, 2019, 4:27am GMT

Camurus - Full Year Report 2018 Markets Insider
STOCKHOLM, Feb. 6, 2019 /PRNewswire/ --'The approval of Buvidal is a major milestone for Camurus and an important validation of our innovative ...
Trailblazing African-Americans Affected by Pancreatic Cancer - Pancreatic Cancer News & Stories

Posted: February 6th, 2019, 10:52pm GMT

Trailblazing African-Americans Affected by Pancreatic Cancer Pancreatic Cancer News & Stories
During African-American History Month, remembering the remarkable achievements of those public figures lost to pancreatic cancer, the third leading cause of ...
Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition - Science

Posted: February 5th, 2019, 5:02pm GMT

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition Science
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with no targeted therapeutic options and in which chemotherapy is only partially effective.
Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition - Science

Posted: February 5th, 2019, 5:02pm GMT

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition Science
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with no targeted therapeutic options and in which chemotherapy is only partially effective.
Will Kareena Kapoor Khan star opposite Irrfan Khan in Hindi Medium 2? - Times Now

Posted: February 5th, 2019, 3:16pm GMT

Will Kareena Kapoor Khan star opposite Irrfan Khan in Hindi Medium 2? Times Now
Kareena Kapoor Khan, who has films like Good News and Takht in her kitty, has reportedly been approached for Hindi Medium 2. Read on for more details.
Why is pancreatic cancer still so hard to treat? - Glenwood Guardian

Posted: February 5th, 2019, 2:00pm GMT

Why is pancreatic cancer still so hard to treat? Glenwood Guardian
Aretha Franklin died today of one of the rarest forms of pancreatic cancer at age 76. Medical advancements have vastly improved survival rates and time alive.
Carcinoid Syndrome Management Market â€“ Industry Outlook, Size, Share, Growth Prospects, Key Opportunities, Trends and Forecasts 2017-2027 - openPR

Posted: February 5th, 2019, 12:12pm GMT

Carcinoid Syndrome Management Market â€“ Industry Outlook, Size, Share, Growth Prospects, Key Opportunities, Trends and Forecasts 2017-2027 openPR
Carcinoid syndrome comprises of signs and symptoms such as flushing of the face, debilitating diarrhea, asthma caused due to vasoconstriction, intestinal ...
Genentech to Develop Xencor IL-15 Cytokines in Immuno-Oncology Partnership - Genetic Engineering & Biotechnology News

Posted: February 5th, 2019, 8:20am GMT

Genentech to Develop Xencor IL-15 Cytokines in Immuno-Oncology Partnership Genetic Engineering & Biotechnology News
Genentech, a member of the Roche group, will partner with Xencor to develop and commercialize its novel IL-15 cytokine therapeutics—including its most ...
Progress in Treating Rare Cancers Named ASCO's Advance of the Year - Targeted Oncology

Posted: February 4th, 2019, 8:27pm GMT

Progress in Treating Rare Cancers Named ASCO's Advance of the Year Targeted Oncology
In recognition of the many advancements that have been made in the past year toward developing new therapies for patients with difficult-to-treat, rare cancers, ...
Neuroendocrine Tumor Treatment Market Segmentation and Analysis by Recent Trends, Development With Top Players - Pfizer, Novartis AG, Ispen, Advanced Accelerator Applications - openPR

Posted: February 4th, 2019, 11:47am GMT

Neuroendocrine Tumor Treatment Market Segmentation and Analysis by Recent Trends, Development With Top Players - Pfizer, Novartis AG, Ispen, Advanced Accelerator Applications openPR
The growing incidence of GI and Lung Neuroendocrine Tumors is a key factor fueling growth of the global neuroendocrine tumor treatment market. According to ...
Student of the Week: World calls International Academy of Macomb's Pearce - The Macomb Daily

Posted: February 4th, 2019, 8:15am GMT

Student of the Week: World calls International Academy of Macomb's Pearce The Macomb Daily
Growing up in a small town like Richmond, Lillian Pearce, by her own admission, hadn't been exposed to much cultural diversity.
Horsewoman returns to family farm, pony club - Bristol Herald Courier

Posted: February 4th, 2019, 3:00am GMT

Horsewoman returns to family farm, pony club Bristol Herald Courier
BRISTOL, Tenn. — A lifelong horsewoman and educator has returned home to her family farm and is taking the reins as leader of the region's Pony Club ...
Who Is Kecalf Franklin? New Details About Aretha Franklin's Son And Why He Was Arrested - YourTango

Posted: February 3rd, 2019, 10:19pm GMT

Who Is Kecalf Franklin? New Details About Aretha Franklin's Son And Why He Was Arrested YourTango
Aretha Franklin's son is behind bars after pleading guilty to drinking and driving. Kecalf Franklin, 28, was arrested in Michigan on Oct. 27, 2018, for driving under ...
CITY BY CITY: A weekly look at the happenings in the places you call home - Gwinnettdailypost.com

Posted: February 2nd, 2019, 6:01pm GMT

CITY BY CITY: A weekly look at the happenings in the places you call home Gwinnettdailypost.com
The Daily Post gives readers a quick look at what's happening in their cities.
Somatostatin Analogs Market 2019 Global Opportunities, Key Players, Competitive and Regional Analysis by Forecast 2023 - Honest Version

Posted: February 2nd, 2019, 7:53am GMT

Somatostatin Analogs Market 2019 Global Opportunities, Key Players, Competitive and Regional Analysis by Forecast 2023 Honest Version
MarketandResearch.biz latest research publication offering titled Global Somatostatin Analogs Market 2018 by Manufacturers, Regions, Type and Application, ...
Report Highlights Clinical Cancer Advances - Pancreatic Cancer News & Stories

Posted: February 2nd, 2019, 10:22pm GMT

Report Highlights Clinical Cancer Advances Pancreatic Cancer News & Stories
ASCO's Clinical Cancer Advances 2019 report highlights progress in the treatment and diagnosis of cancer, including pancreatic cancer. Check out what ...
Califano named physician-in-chief of Moores Cancer Center - The Cancer Letter Publications

Posted: February 1st, 2019, 7:11pm GMT

Califano named physician-in-chief of Moores Cancer Center The Cancer Letter Publications
Joseph Califano was named physician-in-chief of Moores Cancer Center at UC San Diego Health. Califano will retain his roles as professor of surgery and ...
Trending: Christiana's Graham Cancer Center among the first to offer new treatment for rare form of cancer - delawarebusinessnow.com

Posted: February 1st, 2019, 1:07pm GMT

Trending: Christiana's Graham Cancer Center among the first to offer new treatment for rare form of cancer delawarebusinessnow.com
Christiana Care Health System's Helen F. Graham Cancer Center & Research Institute is one of the first sites in the country approved to offer a new treatment ...
Discussions with Leaders: A Conversation Between Steven Larson and Johannes Czernin - Journal of Nuclear Medicine

Posted: February 1st, 2019, 12:17pm GMT

Discussions with Leaders: A Conversation Between Steven Larson and Johannes Czernin Journal of Nuclear Medicine
Steven M. Larson, MD, is the Donna and Benjamin M. Rosen Chair in Radiology; Attending, Molecular Imaging and Therapy *Service*, Department of Radiology; ...
Neuroendocrine Tumor Drug Market 2019 Overview in-Depth Analysis –Ipsen SA, Jiangsu Hengrui Medicine - Honest Version

Posted: February 1st, 2019, 8:07am GMT

Neuroendocrine Tumor Drug Market 2019 Overview in-Depth Analysis –Ipsen SA, Jiangsu Hengrui Medicine Honest Version
The latest release from HTF MI highlights the key market trends impacting the growth of the Global Neuroendocrine Tumor Drug market. The study highlights ...
Neuroendocrine Function Test Market 2019-2025 (Driving Factors, Challenges and Market Trends) - RISReport

Posted: February 1st, 2019, 3:09am GMT

Neuroendocrine Function Test Market 2019-2025 (Driving Factors, Challenges and Market Trends) RISReport
Neuroendocrine Function Test Market Report provides an analytical calculation of the prime challenges faced by this Market currently and in the coming years, ...
Aretha Franklin's son has been jailed since October for a DUI: report - NY Daily News - New York Daily News

Posted: January 31st, 2019, 8:40pm GMT

Aretha Franklin's son has been jailed since October for a DUI: report - NY Daily News New York Daily News
Aretha Franklin's youngest son was reportedly busted for a DUI in late October, just two months after his famous mother died.
Aretha Franklin's son has been jailed since October for a DUI: report - NY Daily News - New York Daily News

Posted: January 31st, 2019, 8:40pm GMT

Aretha Franklin's son has been jailed since October for a DUI: report - NY Daily News New York Daily News
Aretha Franklin's youngest son was reportedly busted for a DUI in late October, just two months after his famous mother died.
ASCO names progress in rare cancer treatment 'Advance of the Year' - Healio

Posted: January 31st, 2019, 8:13pm GMT

ASCO names progress in rare cancer treatment 'Advance of the Year' Healio
ASCO has named progress in treating rare cancers as the cancer Advance of the Year, recognizing major research advances that generated new treatments for ...
ASCO Names Progress in Treating Rare Cancers as Advance of the Year - OncLive

Posted: January 31st, 2019, 8:04pm GMT

ASCO Names Progress in Treating Rare Cancers as Advance of the Year OncLive
Due to major advancements made within the past year in the development of new therapies for patients with difficult-to-treat, rare cancers, ASCO has selected ...
PRRT And The Neuroendocrine Tumor Treatment Algorithm - Cancer Network

Posted: January 31st, 2019, 7:29pm GMT

PRRT And The Neuroendocrine Tumor Treatment Algorithm Cancer Network
Cancer Network spoke with Dr. Shishir Maithel about grading and diagnosing neuroendocrine tumors and how PRRT best fits into the treatment algorithm of ...
Christiana's Graham Cancer Center among the first to offer new treatment for rare form of cancer - delawarebusinessnow.com

Posted: January 31st, 2019, 6:07pm GMT

Christiana's Graham Cancer Center among the first to offer new treatment for rare form of cancer delawarebusinessnow.com
Christiana Care Health System's Helen F. Graham Cancer Center & Research Institute is one of the first sites in the country approved to offer a new treatment ...
Carcinoid Syndrome Diarrhea Treatment Market Competitive analysis - Oak Tribune

Posted: January 31st, 2019, 12:35pm GMT

Carcinoid Syndrome Diarrhea Treatment Market Competitive analysis Oak Tribune
Carcinoid syndrome is caused by secretion of certain harmful chemicals by carcinoid tumors. Carcinoid syndrome may occur due to infection or other related ...
PRRT And The Neuroendocrine Tumor Treatment Algorithm - Cancer Network

Posted: January 31st, 2019, 6:00am GMT

PRRT And The Neuroendocrine Tumor Treatment Algorithm Cancer Network
Cancer Network spoke with Dr. Shishir Maithel about grading and diagnosing neuroendocrine tumors and how PRRT best fits into the treatment algorithm of ...
Aretha Franklin's Son Behind Bars for DUI Arrest After Queen of Soul's Death - The Blast

Posted: January 30th, 2019, 8:55pm GMT

Aretha Franklin's Son Behind Bars for DUI Arrest After Queen of Soul's Death The Blast
Aretha Franklin's youngest son is currently behind bars following a recent arrest for drunk driving and he will not be released until next month.
Global Cancer mTOR Inhibitors Market Growth Forecast to 2024 with Key Players Like Abraxis BioScience, Adimab, Celgene Corporation, Celator Pharmaceuticals, Eli Lilly, Exelixis, GlaxoSmithKline, HEC Pharm, Intellikine, Novartis - Journal Dairy

Posted: January 30th, 2019, 9:04am GMT

Global Cancer mTOR Inhibitors Market Growth Forecast to 2024 with Key Players Like Abraxis BioScience, Adimab, Celgene Corporation, Celator Pharmaceuticals, Eli Lilly, Exelixis, GlaxoSmithKline, HEC Pharm, Intellikine, Novartis Journal Dairy
The Global Cancer mTOR Inhibitors market report is generated with the combination of steps which uses a nice blend of industry insights, practical solutions, ...
The Bachelor: Elyse Dehlbom Uncovers Sarah’s Closet To Colton - TV Season Spoilers

Posted: January 29th, 2019, 4:12am GMT

The Bachelor: Elyse Dehlbom Uncovers Sarah’s Closet To Colton TV Season Spoilers
The Bachelor Elyse Dehlbom's sister Sarah passed away due to neuroendocrine cancer. Sadly, she was also carrying a child when she was diagnosed.
'The Bachelor': Elyse Dehlbom Reveals Details of Sarah's Closet to Colton Underwood - Soap Dirt

Posted: January 28th, 2019, 11:50am GMT

'The Bachelor': Elyse Dehlbom Reveals Details of Sarah's Closet to Colton Underwood Soap Dirt
The Bachelor contestant Elyse Dehlbom recently revealed details of her sister's legacy, Sarah's Closet to Colton Underwood. Elyse's sister passed away from a ...
Reviewing Ultragenyx Pharmaceutical Inc. (RARE)'s and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX)'s results - The FinReviewer

Posted: January 28th, 2019, 2:37am GMT

Reviewing Ultragenyx Pharmaceutical Inc. (RARE)'s and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX)'s results The FinReviewer
Both Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE) and Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) are Biotechnology companies, competing one ...
Crinetics Pharmaceuticals Inc. (CRNX) and Cellular Biomedicine Group Inc. (NASDAQ:CBMG) Comparing side by side - The FinReviewer

Posted: January 25th, 2019, 11:13am GMT

Crinetics Pharmaceuticals Inc. (CRNX) and Cellular Biomedicine Group Inc. (NASDAQ:CBMG) Comparing side by side The FinReviewer
Both Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) and Cellular Biomedicine Group Inc. (NASDAQ:CBMG) are Biotechnology companies, competing one ...
Bavarian Nordic Completes Enrollment of First Stage in Chordoma Phase 2 Trial - Associated Press

Posted: January 25th, 2019, 9:22am GMT

Bavarian Nordic Completes Enrollment of First Stage in Chordoma Phase 2 Trial Associated Press
COPENHAGEN, Denmark, January 25, 2019 - Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) announced today, that the first stage of a Phase 2 study of its ...
Tumor size and grading in sporadic NF-PanNET patients | Digestive and Liver Diseases - MD Linx

Posted: January 25th, 2019, 9:15am GMT

Tumor size and grading in sporadic NF-PanNET patients | Digestive and Liver Diseases MD Linx
Oncology Article: The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age.
Tumor size and grading in sporadic NF-PanNET patients | Digestive and Liver Diseases - MD Linx

Posted: January 25th, 2019, 9:15am GMT

Tumor size and grading in sporadic NF-PanNET patients | Digestive and Liver Diseases MD Linx
Oncology Article: The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age.
Bavarian Nordic Completes Enrollment of First Stage in Chordoma Phase 2 Trial - GlobeNewswire

Posted: January 25th, 2019, 8:59am GMT

Bavarian Nordic Completes Enrollment of First Stage in Chordoma Phase 2 Trial GlobeNewswire
COPENHAGEN, Denmark, January 25, 2019 - Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) announced today, that the first stage of a Phase 2 study of its ...
RadioMedix scores $2 million contract for Targeted Alpha-emitter therapy - DOTmed.com

Posted: January 25th, 2019, 7:49am GMT

RadioMedix scores $2 million contract for Targeted Alpha-emitter therapy DOTmed.com
The National Cancer Institute, part of the National Institutes of Health, has granted RadioMedix a two-year, $2 million Phase II SBIR contract for the clinical ...
Current Treatment Landscape and Emerging Therapies for Pancreatic Cancer - AJMC.com Managed Markets Network

Posted: January 24th, 2019, 8:08pm GMT

Current Treatment Landscape and Emerging Therapies for Pancreatic Cancer AJMC.com Managed Markets Network
Pancreatic cancer remains a disease that is difficult to treat due to a typically late presentation, relatively high resistance to chemotherapy, and lack of effective ...
Crinetics Pharmaceuticals Inc. (CRNX)'s Financial Results Comparing With Aclaris Therapeutics Inc. (NASDAQ:ACRS) – The Financial Examiner - The FinExaminer

Posted: January 24th, 2019, 11:59am GMT

Crinetics Pharmaceuticals Inc. (CRNX)'s Financial Results Comparing With Aclaris Therapeutics Inc. (NASDAQ:ACRS) – The Financial Examiner The FinExaminer
We are contrasting Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) and Aclaris Therapeutics Inc. (NASDAQ:ACRS) on their risk, institutional ownership, analyst ...
Patient Develops Cyclic Cushing’s Syndrome Due to Lung Neuroendocrine Tumor - Cushing's Disease News

Posted: January 24th, 2019, 9:29am GMT

Patient Develops Cyclic Cushing’s Syndrome Due to Lung Neuroendocrine Tumor Cushing's Disease News
Read about how ACTH-releasing tumors outside the pituitary gland may trigger the rare condition of cyclic Cushing's syndrome.
Global Neuroendocrine Tumor Treatment Market Analysis of Rising Business Opportunities with Prominent Investment Ratio by 2026 - World Analytics

Posted: January 23rd, 2019, 8:45pm GMT

Global Neuroendocrine Tumor Treatment Market Analysis of Rising Business Opportunities with Prominent Investment Ratio by 2026 World Analytics
Neuroendocrine tumors (NETs) result from the abnormal growth of neoplasms that originate from cells of the various endocrine glands and nervous systems.
A 43-Year-Old Male With a Soft Tissue Mass - Cancer Network

Posted: January 23rd, 2019, 3:06pm GMT

A 43-Year-Old Male With a Soft Tissue Mass Cancer Network
A 43-year-old man presents with a soft tissue mass in the right leg. A biopsy is obtained. What is your diagnosis?
NET Treatment Market Worth $4.2 Billion by 2026: Acumen Research and Consulting - GlobeNewswire

Posted: January 23rd, 2019, 1:00pm GMT

NET Treatment Market Worth $4.2 Billion by 2026: Acumen Research and Consulting GlobeNewswire
Acumen Research and Consulting delivers detailed insights into the Neuroendocrine Tumor Treatment Market, in its upcoming outlook titled, ' NET Treatment ...
Non-Small Cell Lung Cancer Market 2018 Growth Statistics ,Latest Trend and Future Analysis Till 2026 - World Analytics

Posted: January 23rd, 2019, 12:34pm GMT

Non-Small Cell Lung Cancer Market 2018 Growth Statistics ,Latest Trend and Future Analysis Till 2026 World Analytics
Small cell lung cancer and non-small cell lung cancer are the two main types of lung cancer. As per the stats of Lung Cancer Alliance (leading nonprofit ...
A 43-Year-Old Male With a Soft Tissue Mass - Cancer Network

Posted: January 23rd, 2019, 6:00am GMT

A 43-Year-Old Male With a Soft Tissue Mass Cancer Network
A 43-year-old man presents with a soft tissue mass in the right leg. A biopsy is obtained. What is your diagnosis?
No Survival Improvement Seen With Ibrutinib Combination in Pancreatic Cancer - Targeted Oncology

Posted: January 23rd, 2019, 12:41am GMT

No Survival Improvement Seen With Ibrutinib Combination in Pancreatic Cancer Targeted Oncology
Frontline treatment with ibrutinib plus nab-paclitaxel/gemcitabine did not have a statistically significant benefit in progression-free survival or overall survival ...
Ibrutinib Combo Falls Short in Pancreatic Cancer - OncLive

Posted: January 22nd, 2019, 2:06pm GMT

Ibrutinib Combo Falls Short in Pancreatic Cancer OncLive
The frontline combination of ibrutinib (Imbruvica) and nab-paclitaxel (Abraxane)/gemcitabine did not show a statistically significant benefit in progression-free or ...
Global Neuroendocrine Tumor Treatment Market Analysis of Rising Business Opportunities with Prominent Investment Ratio by 2026 - Ace Newz

Posted: January 22nd, 2019, 12:45pm GMT

Global Neuroendocrine Tumor Treatment Market Analysis of Rising Business Opportunities with Prominent Investment Ratio by 2026 Ace Newz
There are various other types of neuroendocrine tumors that may occur across various parts of the body and have different growth patterns.
Elyse Told Colton About Her Sister On 'The Bachelor' & It Brought Them Closer Together - Bustle

Posted: January 22nd, 2019, 6:00am GMT

Elyse Told Colton About Her Sister On 'The Bachelor' & It Brought Them Closer Together Bustle
Three weeks in, Colton Underwood is finally getting to know his contestants better, even if that comes with hearing some pretty heartbreaking stories. During ...
Neuroendocrine Tumor Treatment Market – Outlook on Product Growth 2028 - Press Release - Digital Journal

Posted: January 22nd, 2019, 2:55am GMT

Neuroendocrine Tumor Treatment Market – Outlook on Product Growth 2028 - Press Release Digital Journal
[https:] Neuroendocrine Tumor Treatment Market: Drivers and RestraintsOne of the major ...
Rocks for Hope Creator Dies After Cancer Battle - Spectrum News

Posted: January 21st, 2019, 9:46pm GMT

Rocks for Hope Creator Dies After Cancer Battle Spectrum News
A Raeford woman who created "Rocks for Hope" died of cancer Sunday night.
Non-Small Cell Lung Cancer Market – How the Market Will Witness Substantial Growth by 2026 - Ace Newz

Posted: January 21st, 2019, 11:58am GMT

Non-Small Cell Lung Cancer Market – How the Market Will Witness Substantial Growth by 2026 Ace Newz
Increasing research and development on drugs and the prevalence of lung cancer are the major factors driving the growth of non-small cell lung cancer market.

Google - Merkel Cell Cancer

NantKwest Inc. (NK) and Oncolytics Biotech Inc. (NASDAQ:ONCY) Comparison side by side - The Hi New Ulm

Posted: February 16th, 2019, 2:17am GMT

NantKwest Inc. (NK) and Oncolytics Biotech Inc. (NASDAQ:ONCY) Comparison side by side The Hi New Ulm
Both NantKwest Inc. (NASDAQ:NK) and Oncolytics Biotech Inc. (NASDAQ:ONCY) compete on a level playing field in the Biotechnology industry. We will ...
NantKwest Inc. (NK)'s Financial Results Comparing With Sesen Bio Inc. (NASDAQ:SESN) - Port Courier

Posted: February 16th, 2019, 11:39pm GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Sesen Bio Inc. (NASDAQ:SESN) Port Courier
This is therefore a comparing of the analyst recommendations, institutional ownership, profitability, risk, dividends, earnings and valuation in NantKwest Inc.
Novus Therapeutics Inc. (NVUS) and Immune Design Corp. (NASDAQ:IMDZ) Comparison side by side - The Yomi Blog

Posted: February 16th, 2019, 11:04pm GMT

Novus Therapeutics Inc. (NVUS) and Immune Design Corp. (NASDAQ:IMDZ) Comparison side by side The Yomi Blog
Both Novus Therapeutics Inc. (NASDAQ:NVUS) and Immune Design Corp. (NASDAQ:IMDZ) are each other's competitor in the Biotechnology industry. Thus the ...
Comparison of NantKwest Inc. (NK) and Spring Bank Pharmaceuticals Inc. (NASDAQ:SBPH) - The Moveefy

Posted: February 15th, 2019, 6:48pm GMT

Comparison of NantKwest Inc. (NK) and Spring Bank Pharmaceuticals Inc. (NASDAQ:SBPH) The Moveefy
NantKwest Inc. (NASDAQ:NK) and Spring Bank Pharmaceuticals Inc. (NASDAQ:SBPH), are influenced by compare since they are both players in the ...
NantKwest Inc. (NK)'s Financial Results Comparing With Ophthotech Corporation (NASDAQ:OPHT) - The Yomi Blog

Posted: February 15th, 2019, 6:47pm GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Ophthotech Corporation (NASDAQ:OPHT) The Yomi Blog
As Biotechnology companies, NantKwest Inc. (NASDAQ:NK) and Ophthotech Corporation (NASDAQ:OPHT) are our subject to compare. And more specifically ...
Nantkwest Inc (NASDAQ:NK) Sellers Rose By 5.49% Their Shorts As Of Feb 15, 2019 - K Reviewer

Posted: February 15th, 2019, 4:34pm GMT

Nantkwest Inc (NASDAQ:NK) Sellers Rose By 5.49% Their Shorts As Of Feb 15, 2019 K Reviewer
Change of 5.49% for Nantkwest Inc (NASDAQ:NK)'s short interest was noted. In February was published NK's total 2.67 million short interest by FINRA.
On Feb 15, 2019 Nantkwest Inc (NASDAQ:NK) Shorts Strengthened By 5.49% - The EN Bulletin

Posted: February 15th, 2019, 4:25pm GMT

On Feb 15, 2019 Nantkwest Inc (NASDAQ:NK) Shorts Strengthened By 5.49% The EN Bulletin
Change of 5.49% for Nantkwest Inc (NASDAQ:NK)'s shorted shares was registered. In February was published NK's total 2.67M shorted shares by FINRA.
Reviewing Immune Design Corp. (IMDZ)'s and Progenics Pharmaceuticals Inc. (NASDAQ:PGNX)'s results - The FinHeadLines

Posted: February 15th, 2019, 11:43am GMT

Reviewing Immune Design Corp. (IMDZ)'s and Progenics Pharmaceuticals Inc. (NASDAQ:PGNX)'s results The FinHeadLines
Immune Design Corp. (NASDAQ:IMDZ) and Progenics Pharmaceuticals Inc. (NASDAQ:PGNX), are influenced by contrast since they are both players in the.
FDA Grants Priority Review to Merck's Supplemental Biologics License Application for KEYTRUDA® (pembrolizumab) in Combination with Inlyta® (axitinib) as First-Line Treatment for Advanced Renal Cell Carcinoma - Associated Press

Posted: February 15th, 2019, 10:19am GMT

FDA Grants Priority Review to Merck's Supplemental Biologics License Application for KEYTRUDA® (pembrolizumab) in Combination with Inlyta® (axitinib) as First-Line Treatment for Advanced Renal Cell Carcinoma Associated Press
KENILWORTH, N.J.--(BUSINESS WIRE)--Feb 15, 2019--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the ...
Reviewing Ovid Therapeutics Inc. (OVID)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results - EN Digest

Posted: February 15th, 2019, 9:40am GMT

Reviewing Ovid Therapeutics Inc. (OVID)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results EN Digest
As Biotechnology companies, Ovid Therapeutics Inc. (NASDAQ:OVID) and Immune Design Corp. (NASDAQ:IMDZ) are our subject to contrast. And more ...
Monoclonal Antibody Therapeutics Market | Industry Challenges, Growth and Forecast by 2026 - Crypto News Today

Posted: February 15th, 2019, 4:12am GMT

Monoclonal Antibody Therapeutics Market | Industry Challenges, Growth and Forecast by 2026 Crypto News Today
Monoclonal antibodies Robust pipeline, success of monoclonal antibodies such as Humira (AbbVie, Inc.) and therapeutic advantages offered by these drugs ...
Anticipated $-0.31 EPS for NantKwest, Inc. (NK) as of March, 11 - The EN Bulletin

Posted: February 15th, 2019, 2:32am GMT

Anticipated $-0.31 EPS for NantKwest, Inc. (NK) as of March, 11 The EN Bulletin
NantKwest, Inc. (NASDAQ:NK)'s quarterly earnings will be reported on March, 11., RTT reports. earnings per share of $-0.31 is 0.00 % from 2018's $-0.31 EPS.
Comparing of Immune Design Corp. (IMDZ) and Strongbridge Biopharma plc (NASDAQ:SBBP) - EN Digest

Posted: February 15th, 2019, 1:18am GMT

Comparing of Immune Design Corp. (IMDZ) and Strongbridge Biopharma plc (NASDAQ:SBBP) EN Digest
As Biotechnology companies, Immune Design Corp. (NASDAQ:IMDZ) and Strongbridge Biopharma plc (NASDAQ:SBBP) are our subject to compare. And more ...
NantKwest Inc. (NK) and Unum Therapeutics Inc. (NASDAQ:UMRX) Comparison side by side - The Hi New Ulm

Posted: February 15th, 2019, 11:32pm GMT

NantKwest Inc. (NK) and Unum Therapeutics Inc. (NASDAQ:UMRX) Comparison side by side The Hi New Ulm
NantKwest Inc. (NASDAQ:NK) and Unum Therapeutics Inc. (NASDAQ:UMRX) compete against each other in the Biotechnology sector. We will compare them ...
Reviewing OncoSec Medical Incorporated (ONCS)'s and Biohaven Pharmaceutical Holding Company Ltd. (NYSE:BHVN)'s results - D Minute

Posted: February 15th, 2019, 11:07pm GMT

Reviewing OncoSec Medical Incorporated (ONCS)'s and Biohaven Pharmaceutical Holding Company Ltd. (NYSE:BHVN)'s results D Minute
Both OncoSec Medical Incorporated (NASDAQ:ONCS) and Biohaven Pharmaceutical Holding Company Ltd. (NYSE:BHVN) are Biotechnology companies, ...
Comparison of Acasti Pharma Inc. (ACST) and Immune Design Corp. (NASDAQ:IMDZ) - Lives Advice

Posted: February 15th, 2019, 10:47pm GMT

Comparison of Acasti Pharma Inc. (ACST) and Immune Design Corp. (NASDAQ:IMDZ) Lives Advice
Acasti Pharma Inc. (NASDAQ:ACST) and Immune Design Corp. (NASDAQ:IMDZ), both competing one another are Biotechnology companies. We will contrast ...
Immuno-oncology in 2019: the rapid evolution continues - PMLiVE

Posted: February 15th, 2019, 10:16pm GMT

Immuno-oncology in 2019: the rapid evolution continues PMLiVE
Cancer treatment has been transformed in the last few years, thanks to that now-familiar generation of drugs which strip tumours of their 'cloaking device', ...
Comparing of Puma Biotechnology Inc. (PBYI) and OncoSec Medical Incorporated (NASDAQ:ONCS) - The Yomi Blog

Posted: February 14th, 2019, 9:37pm GMT

Comparing of Puma Biotechnology Inc. (PBYI) and OncoSec Medical Incorporated (NASDAQ:ONCS) The Yomi Blog
Puma Biotechnology Inc. (NASDAQ:PBYI) and OncoSec Medical Incorporated (NASDAQ:ONCS), are influenced by contrast since they are both players in the.
NantKwest Inc. (NK)'s Financial Results Comparing With Cytori Therapeutics Inc. (NASDAQ:CYTX) - Lives Advice

Posted: February 14th, 2019, 7:32pm GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Cytori Therapeutics Inc. (NASDAQ:CYTX) Lives Advice
Both NantKwest Inc. (NASDAQ:NK) and Cytori Therapeutics Inc. (NASDAQ:CYTX) are Biotechnology companies, competing one another. We will compare their ...
Reviewing NantKwest Inc. (NK)'s and CymaBay Therapeutics Inc. (NASDAQ:CBAY)'s results - The FinHeadLines

Posted: February 14th, 2019, 7:32pm GMT

Reviewing NantKwest Inc. (NK)'s and CymaBay Therapeutics Inc. (NASDAQ:CBAY)'s results The FinHeadLines
We will be comparing the differences between NantKwest Inc. (NASDAQ:NK) and CymaBay Therapeutics Inc. (NASDAQ:CBAY) as far as profitability, ...
Comparison of Immune Design Corp. (IMDZ) and Scholar Rock Holding Corporation (NASDAQ:SRRK) - The Hi New Ulm

Posted: February 14th, 2019, 7:18pm GMT

Comparison of Immune Design Corp. (IMDZ) and Scholar Rock Holding Corporation (NASDAQ:SRRK) The Hi New Ulm
Since Immune Design Corp. (NASDAQ:IMDZ) and Scholar Rock Holding Corporation (NASDAQ:SRRK) are part of the Biotechnology industry, they are ...
Analysts See $-0.31 EPS for NantKwest, Inc. (NK); Sandy Spring Bank Has Boosted Thermo Fisher Scientific (TMO) Holding By $416,508 - EN Digest

Posted: February 14th, 2019, 5:18pm GMT

Analysts See $-0.31 EPS for NantKwest, Inc. (NK); Sandy Spring Bank Has Boosted Thermo Fisher Scientific (TMO) Holding By $416,508 EN Digest
Sandy Spring Bank increased Thermo Fisher Scientific Inc (TMO) stake by 11.24% reported in 2018Q3 SEC filing. Sandy Spring Bank acquired 1,707 shares as ...
Medical World News: Regulatory Updates - AJMC.com Managed Markets Network

Posted: February 14th, 2019, 4:10pm GMT

Medical World News: Regulatory Updates AJMC.com Managed Markets Network
The FDA recently granted accelerated approval1 to pembrolizumab (Keytruda) for adult and pediatric patients with recurrent locally advanced or metastatic ...
Comparison of Kadmon Holdings Inc. (KDMN) and Immune Design Corp. (NASDAQ:IMDZ) - Port Courier

Posted: February 14th, 2019, 1:45pm GMT

Comparison of Kadmon Holdings Inc. (KDMN) and Immune Design Corp. (NASDAQ:IMDZ) Port Courier
Kadmon Holdings Inc. (NYSE:KDMN) and Immune Design Corp. (NASDAQ:IMDZ) have been rivals in the Biotechnology for quite some time. Below is a review ...
NantKwest Inc. (NK) and Eloxx Pharmaceuticals Inc. (NASDAQ:ELOX) Comparing side by side - The Hi New Ulm

Posted: February 14th, 2019, 1:01pm GMT

NantKwest Inc. (NK) and Eloxx Pharmaceuticals Inc. (NASDAQ:ELOX) Comparing side by side The Hi New Ulm
This is therefore a contrasting of the risk, institutional ownership, analyst recommendations, profitability, dividends, earnings and valuation in NantKwest Inc.
Merck Increases Focus on Advanced Prostate Cancer, Expanding Immuno-Oncology Program with Three New Phase 3 Trials - Business Wire

Posted: February 14th, 2019, 9:45am GMT

Merck Increases Focus on Advanced Prostate Cancer, Expanding Immuno-Oncology Program with Three New Phase 3 Trials Business Wire
Research Program Expanded Based on Promising Data Shown with KEYTRUDA® (pembrolizumab) in Combination with LYNPARZA® (olaparib), ...
Comparing of Oramed Pharmaceuticals Inc. (ORMP) and Immune Design Corp. (NASDAQ:IMDZ) - The Moveefy

Posted: February 14th, 2019, 8:29am GMT

Comparing of Oramed Pharmaceuticals Inc. (ORMP) and Immune Design Corp. (NASDAQ:IMDZ) The Moveefy
Oramed Pharmaceuticals Inc. (NASDAQ:ORMP) and Immune Design Corp. (NASDAQ:IMDZ) have been rivals in the Biotechnology for quite some time. Below is ...
Pfizer (PFE) Position Has Boosted by Glenmede Trust Company Na; Highland Capital Management Lifted Mckesson Hboc (MCK) Stake by $404,712; Stock Price Declined - The FinReviewer

Posted: February 14th, 2019, 8:23am GMT

Pfizer (PFE) Position Has Boosted by Glenmede Trust Company Na; Highland Capital Management Lifted Mckesson Hboc (MCK) Stake by $404,712; Stock Price Declined The FinReviewer
Glenmede Trust Company Na increased its stake in Pfizer Inc (PFE) by 55.95% based on its latest 2018Q3 regulatory filing with the SEC. Glenmede Trust ...
Contrasting of Citius Pharmaceuticals Inc. (CTXR) and NantKwest Inc. (NASDAQ:NK) - The FinReviewer

Posted: February 14th, 2019, 3:39am GMT

Contrasting of Citius Pharmaceuticals Inc. (CTXR) and NantKwest Inc. (NASDAQ:NK) The FinReviewer
Both Citius Pharmaceuticals Inc. (NASDAQ:CTXR) and NantKwest Inc. (NASDAQ:NK) compete on a level playing field in the Biotechnology industry. We will ...
Reviewing OncoSec Medical Incorporated (ONCS)'s and uniQure NV (NASDAQ:QURE)'s results - The Hi New Ulm

Posted: February 14th, 2019, 3:38am GMT

Reviewing OncoSec Medical Incorporated (ONCS)'s and uniQure NV (NASDAQ:QURE)'s results The Hi New Ulm
As Biotechnology companies, OncoSec Medical Incorporated (NASDAQ:ONCS) and uniQure N.V. (NASDAQ:QURE) are our subject to compare. And more ...
Reviewing Aptinyx Inc. (APTX)'s and NantKwest Inc. (NASDAQ:NK)'s results - The Yomi Blog

Posted: February 14th, 2019, 2:39am GMT

Reviewing Aptinyx Inc. (APTX)'s and NantKwest Inc. (NASDAQ:NK)'s results The Yomi Blog
As Biotechnology companies, Aptinyx Inc. (NASDAQ:APTX) and NantKwest Inc. (NASDAQ:NK) are our subject to compare. And more specifically their risk, ...
CytRx Corporation (CYTR)'s Financial Results Comparing With NantKwest Inc. (NASDAQ:NK) - The FinHeadLines

Posted: February 14th, 2019, 1:36am GMT

CytRx Corporation (CYTR)'s Financial Results Comparing With NantKwest Inc. (NASDAQ:NK) The FinHeadLines
We will be contrasting the differences between CytRx Corporation (NASDAQ:CYTR) and NantKwest Inc. (NASDAQ:NK) as far as dividends, analyst ...
NantKwest Inc. (NK)'s Financial Results Comparing With Molecular Templates Inc. (NASDAQ:MTEM) - Thе Mоnіtоr

Posted: February 14th, 2019, 12:28am GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Molecular Templates Inc. (NASDAQ:MTEM) Thе Mоnіtоr
We are contrasting NantKwest Inc. (NASDAQ:NK) and Molecular Templates Inc. (NASDAQ:MTEM) on their institutional ownership, profitability, risk, dividends,
Immune Design Corp. (IMDZ) EPS Estimated At $-0.29 | Thorold News - Thorold News

Posted: February 13th, 2019, 8:40pm GMT

Immune Design Corp. (IMDZ) EPS Estimated At $-0.29 | Thorold News Thorold News
Investors sentiment decreased to 1.18 in 2018 Q3. Its down 0.77, from 1.95 in 2018Q2. It worsened, as 10 investors sold Immune Design Corp. shares while 18.
NantKwest, Inc. (NK) EPS Estimated At $-0.31; First Long Island Investors Trimmed Abbott Labs Com (ABT) Stake By $825,265 - Thе Mоnіtоr

Posted: February 13th, 2019, 7:32pm GMT

NantKwest, Inc. (NK) EPS Estimated At $-0.31; First Long Island Investors Trimmed Abbott Labs Com (ABT) Stake By $825,265 Thе Mоnіtоr
Analysts expect NantKwest, Inc. (NASDAQ:NK) to report $-0.31 EPS on March, 11.They anticipate $0.00 EPS change or 0.00% from last quarter's $-0.31 EPS.
NantKwest, Inc. (NK) EPS Estimated At $-0.31 | Thorold News - Thorold News

Posted: February 13th, 2019, 7:26pm GMT

NantKwest, Inc. (NK) EPS Estimated At $-0.31 | Thorold News Thorold News
Analysts expect NantKwest, Inc. (NASDAQ:NK) to report $-0.31 EPS on March, 11.They anticipate $0.00 EPS change or 0.00 % from last quarter's $-0.31 EPS.
Matinas BioPharma Holdings Inc. (MTNB) and NantKwest Inc. (NASDAQ:NK) Comparing side by side - The Moveefy

Posted: February 13th, 2019, 7:20pm GMT

Matinas BioPharma Holdings Inc. (MTNB) and NantKwest Inc. (NASDAQ:NK) Comparing side by side The Moveefy
Matinas BioPharma Holdings Inc. (NYSEAMERICAN:MTNB) and NantKwest Inc. (NASDAQ:NK) are two firms in the Biotechnology that compete against each ...
Reviewing Arbutus Biopharma Corporation (ABUS)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results - D Minute

Posted: February 13th, 2019, 6:10pm GMT

Reviewing Arbutus Biopharma Corporation (ABUS)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results D Minute
Arbutus Biopharma Corporation (NASDAQ:ABUS) and Immune Design Corp. (NASDAQ:IMDZ), both competing one another are Biotechnology companies.
Contrasting of Moleculin Biotech Inc. (MBRX) and Immune Design Corp. (NASDAQ:IMDZ) - Port Courier

Posted: February 13th, 2019, 5:57pm GMT

Contrasting of Moleculin Biotech Inc. (MBRX) and Immune Design Corp. (NASDAQ:IMDZ) Port Courier
As Biotechnology businesses, Moleculin Biotech Inc. (NASDAQ:MBRX) and Immune Design Corp. (NASDAQ:IMDZ), are affected by compare. This especially ...
Comparison of NantKwest Inc. (NK) and Zymeworks Inc. (NYSE:ZYME) - Thе Mоnіtоr

Posted: February 13th, 2019, 5:30pm GMT

Comparison of NantKwest Inc. (NK) and Zymeworks Inc. (NYSE:ZYME) Thе Mоnіtоr
Since NantKwest Inc. (NASDAQ:NK) and Zymeworks Inc. (NYSE:ZYME) are part of the Biotechnology industry, they are influenced by contrast. The influences.
On March, 11 Analysts See $-0.31 EPS for NantKwest, Inc. (NK) - K Reviewer

Posted: February 13th, 2019, 4:44pm GMT

On March, 11 Analysts See $-0.31 EPS for NantKwest, Inc. (NK) K Reviewer
NantKwest, Inc. (NASDAQ:NK)'s earnings report is awaited on March, 11., according to RTT. Analysts forecast $-0.31 EPS. That's $0.00 or 0.00 % from 2018's ...
Reviewing NantKwest Inc. (NK)'s and Kala Pharmaceuticals Inc. (NASDAQ:KALA)'s results - The FinHeadLines

Posted: February 13th, 2019, 3:24pm GMT

Reviewing NantKwest Inc. (NK)'s and Kala Pharmaceuticals Inc. (NASDAQ:KALA)'s results The FinHeadLines
As Biotechnology businesses, NantKwest Inc. (NASDAQ:NK) and Kala Pharmaceuticals Inc. (NASDAQ:KALA), are affected by compare. This especially applies ...
Reviewing Unum Therapeutics Inc. (UMRX)'s and NantKwest Inc. (NASDAQ:NK)'s results - The FinReviewer

Posted: February 13th, 2019, 3:06pm GMT

Reviewing Unum Therapeutics Inc. (UMRX)'s and NantKwest Inc. (NASDAQ:NK)'s results The FinReviewer
Unum Therapeutics Inc. (NASDAQ:UMRX) and NantKwest Inc. (NASDAQ:NK), are influenced by compare since they are both players in the Biotechnology.
Immuron Limited (IMRN) and NantKwest Inc. (NASDAQ:NK) Contrasting side by side - Port Courier

Posted: February 13th, 2019, 2:36pm GMT

Immuron Limited (IMRN) and NantKwest Inc. (NASDAQ:NK) Contrasting side by side Port Courier
Since Immuron Limited (NASDAQ:IMRN) and NantKwest Inc. (NASDAQ:NK) are part of the Biotechnology industry, they are influenced by compare.
Rubius Therapeutics Inc. (RUBY)'s Financial Results Comparing With Immune Design Corp. (NASDAQ:IMDZ) - Port Courier

Posted: February 13th, 2019, 9:40am GMT

Rubius Therapeutics Inc. (RUBY)'s Financial Results Comparing With Immune Design Corp. (NASDAQ:IMDZ) Port Courier
As Biotechnology companies, Rubius Therapeutics Inc. (NASDAQ:RUBY) and Immune Design Corp. (NASDAQ:IMDZ) are our subject to compare. And more ...
Reviewing Anavex Life Sciences Corp. (AVXL)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results - Lives Advice

Posted: February 13th, 2019, 9:28am GMT

Reviewing Anavex Life Sciences Corp. (AVXL)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results Lives Advice
Anavex Life Sciences Corp. (NASDAQ:AVXL) and OncoSec Medical Incorporated (NASDAQ:ONCS), both competing one another are Biotechnology companies.
OncoSec Medical Incorporated (ONCS) and Synthetic Biologics Inc. (NYSEAMERICAN:SYN) Comparison side by side - Port Courier

Posted: February 13th, 2019, 8:38am GMT

OncoSec Medical Incorporated (ONCS) and Synthetic Biologics Inc. (NYSEAMERICAN:SYN) Comparison side by side Port Courier
Both OncoSec Medical Incorporated (NASDAQ:ONCS) and Synthetic Biologics Inc. (NYSEAMERICAN:SYN) compete on a level playing field in the ...
OncoMed Pharmaceuticals Inc. (OMED)'s Financial Results Comparing With NantKwest Inc. (NASDAQ:NK) - The Hi New Ulm

Posted: February 13th, 2019, 5:01am GMT

OncoMed Pharmaceuticals Inc. (OMED)'s Financial Results Comparing With NantKwest Inc. (NASDAQ:NK) The Hi New Ulm
Since OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) and NantKwest Inc. (NASDAQ:NK) are part of the Biotechnology industry, they are influenced by ...
NantKwest Inc. (NK)'s Financial Results Comparing With Idera Pharmaceuticals Inc. (NASDAQ:IDRA) - The Moveefy

Posted: February 13th, 2019, 4:45am GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Idera Pharmaceuticals Inc. (NASDAQ:IDRA) The Moveefy
As Biotechnology companies, NantKwest Inc. (NASDAQ:NK) and Idera Pharmaceuticals Inc. (NASDAQ:IDRA) are our subject to contrast. And more specifically ...
Reviewing Immune Design Corp. (IMDZ)'s and Brainstorm Cell Therapeutics Inc. (NASDAQ:BCLI)'s results - Port Courier

Posted: February 13th, 2019, 12:20am GMT

Reviewing Immune Design Corp. (IMDZ)'s and Brainstorm Cell Therapeutics Inc. (NASDAQ:BCLI)'s results Port Courier
Since Immune Design Corp. (NASDAQ:IMDZ) and Brainstorm Cell Therapeutics Inc. (NASDAQ:BCLI) are part of the Biotechnology industry, they are influenced ...
NantKwest Inc. (NK) and MeiraGTx Holdings plc (NASDAQ:MGTX) Comparing side by side - Port Courier

Posted: February 13th, 2019, 10:38pm GMT

NantKwest Inc. (NK) and MeiraGTx Holdings plc (NASDAQ:MGTX) Comparing side by side Port Courier
Both NantKwest Inc. (NASDAQ:NK) and MeiraGTx Holdings plc (NASDAQ:MGTX) are Biotechnology companies, competing one another. We will contrast their.
Reviewing NantKwest Inc. (NK)'s and Marker Therapeutics Inc. (NASDAQ:MRKR)'s results - D Minute

Posted: February 13th, 2019, 10:34pm GMT

Reviewing NantKwest Inc. (NK)'s and Marker Therapeutics Inc. (NASDAQ:MRKR)'s results D Minute
We will be comparing the differences between NantKwest Inc. (NASDAQ:NK) and Marker Therapeutics Inc. (NASDAQ:MRKR) as far as profitability, analyst.
Form 424B5 MACROGENICS INC - StreetInsider.com

Posted: February 12th, 2019, 7:34pm GMT

Form 424B5 MACROGENICS INC StreetInsider.com
News and research before you hear about it on CNBC and others. Claim your 2-week free trial to StreetInsider Premium here.
Immune Design Corp. (IMDZ) EPS Estimated At $-0.29; Oncolytics Biotech Inchares (ONCY) Shorts Decreased By 9.22% - EN Digest

Posted: February 12th, 2019, 6:21pm GMT

Immune Design Corp. (IMDZ) EPS Estimated At $-0.29; Oncolytics Biotech Inchares (ONCY) Shorts Decreased By 9.22% EN Digest
Analysts expect Immune Design Corp. (NASDAQ:IMDZ) to report $-0.29 EPS on March, 13.They anticipate $0.00 EPS change or 0.00% from last quarter's $-0.29 ...
Analysts See $-0.31 EPS for NantKwest, Inc. (NK); NEXOPTIC TECHNOLOGY COMMON SHARES (NXOPF) Shorts Raised By 69.94% - Port Courier

Posted: February 12th, 2019, 5:47pm GMT

Analysts See $-0.31 EPS for NantKwest, Inc. (NK); NEXOPTIC TECHNOLOGY COMMON SHARES (NXOPF) Shorts Raised By 69.94% Port Courier
Analysts expect NantKwest, Inc. (NASDAQ:NK) to report $-0.31 EPS on March, 11.They anticipate $0.00 EPS change or 0.00% from last quarter's $-0.31 EPS.
Reviewing Ophthotech Corporation (OPHT)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results - The Hi New Ulm

Posted: February 12th, 2019, 4:42pm GMT

Reviewing Ophthotech Corporation (OPHT)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results The Hi New Ulm
Both Ophthotech Corporation (NASDAQ:OPHT) and OncoSec Medical Incorporated (NASDAQ:ONCS) are Biotechnology companies, competing one another.
Pfizer sBLA for Kidney Cancer Drug Combo Gets Priority Review - Yahoo News

Posted: February 12th, 2019, 1:10pm GMT

Pfizer sBLA for Kidney Cancer Drug Combo Gets Priority Review Yahoo News
Pfizer (PFE)/Merck KGaA's label expansion application for Bavencio as a treatment for advanced kidney cancer in combination with Inlyta gets priority review in ...
Community Financial Services Group Decreased By $449,650 Its Exxon Mobil (XOM) Position; Immune Design Corp. (IMDZ) Sentiment Is 1.18 - D Minute

Posted: February 12th, 2019, 12:32pm GMT

Community Financial Services Group Decreased By $449,650 Its Exxon Mobil (XOM) Position; Immune Design Corp. (IMDZ) Sentiment Is 1.18 D Minute
Community Financial Services Group Llc decreased Exxon Mobil Corp (XOM) stake by 28.47% reported in 2018Q3 SEC filing. Community Financial Services ...
Comparing of Rhythm Pharmaceuticals Inc. (RYTM) and Immune Design Corp. (NASDAQ:IMDZ) - The FinHeadLines

Posted: February 12th, 2019, 9:20am GMT

Comparing of Rhythm Pharmaceuticals Inc. (RYTM) and Immune Design Corp. (NASDAQ:IMDZ) The FinHeadLines
Both Rhythm Pharmaceuticals Inc. (NASDAQ:RYTM) and Immune Design Corp. (NASDAQ:IMDZ) are Biotechnology companies, competing one another. We will ...
OncoSec Medical Incorporated (ONCS) and Corbus Pharmaceuticals Holdings Inc. (NASDAQ:CRBP) Comparing side by side - The FinHeadLines

Posted: February 12th, 2019, 1:04am GMT

OncoSec Medical Incorporated (ONCS) and Corbus Pharmaceuticals Holdings Inc. (NASDAQ:CRBP) Comparing side by side The FinHeadLines
This is a contrast between OncoSec Medical Incorporated (NASDAQ:ONCS) and Corbus Pharmaceuticals Holdings Inc. (NASDAQ:CRBP) based on their ...
Contrasting of Immune Design Corp. (IMDZ) and Arcturus Therapeutics Ltd. (NASDAQ:ARCT) - The FinHeadLines

Posted: February 12th, 2019, 11:24pm GMT

Contrasting of Immune Design Corp. (IMDZ) and Arcturus Therapeutics Ltd. (NASDAQ:ARCT) The FinHeadLines
Immune Design Corp. (NASDAQ:IMDZ) and Arcturus Therapeutics Ltd. (NASDAQ:ARCT), both competing one another are Biotechnology companies. We will ...
Arvinas Holding Company LLC (ARVN) and NantKwest Inc. (NASDAQ:NK) Comparison side by side - The Moveefy

Posted: February 12th, 2019, 11:22pm GMT

Arvinas Holding Company LLC (ARVN) and NantKwest Inc. (NASDAQ:NK) Comparison side by side The Moveefy
Arvinas Holding Company LLC (NASDAQ:ARVN) and NantKwest Inc. (NASDAQ:NK) compete against each other in the Biotechnology sector. We will contrast ...
Reviewing NantKwest Inc. (NK)'s and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR)'s results - The FinExaminer

Posted: February 12th, 2019, 11:19pm GMT

Reviewing NantKwest Inc. (NK)'s and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR)'s results The FinExaminer
NantKwest Inc. (NASDAQ:NK) and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) compete against each other in the Biotechnology sector. We will compare ...
Reviewing Immune Design Corp. (IMDZ)'s and Celsion Corporation (NASDAQ:CLSN)'s results - The FinReviewer

Posted: February 12th, 2019, 11:03pm GMT

Reviewing Immune Design Corp. (IMDZ)'s and Celsion Corporation (NASDAQ:CLSN)'s results The FinReviewer
Both Immune Design Corp. (NASDAQ:IMDZ) and Celsion Corporation (NASDAQ:CLSN) compete on a level playing field in the Biotechnology industry. We will ...
Reviewing Tesaro Inc. (TSRO)'s and NantKwest Inc. (NASDAQ:NK)'s results - The FinReviewer

Posted: February 11th, 2019, 9:39pm GMT

Reviewing Tesaro Inc. (TSRO)'s and NantKwest Inc. (NASDAQ:NK)'s results The FinReviewer
Both Tesaro Inc. (NASDAQ:TSRO) and NantKwest Inc. (NASDAQ:NK) compete on a level playing field in the Biotechnology industry. We will evaluate their.
$-0.31 EPS Expected for NantKwest, Inc. (NK); PELE MOUNTAIN RESOURCES (GOLDF) Sellers Decreased By 47.51% Their Shorts - The Yomi Blog

Posted: February 11th, 2019, 5:36pm GMT

$-0.31 EPS Expected for NantKwest, Inc. (NK); PELE MOUNTAIN RESOURCES (GOLDF) Sellers Decreased By 47.51% Their Shorts The Yomi Blog
PELE MOUNTAIN RESOURCES INC (OTCMKTS:GOLDF) had a decrease of 47.51% in short interest. GOLDF's SI was 13,700 shares in February as released ...
NantKwest Inc. (NK) and ChemoCentryx Inc. (NASDAQ:CCXI) Comparison side by side - Port Courier

Posted: February 11th, 2019, 1:52pm GMT

NantKwest Inc. (NK) and ChemoCentryx Inc. (NASDAQ:CCXI) Comparison side by side Port Courier
Both NantKwest Inc. (NASDAQ:NK) and ChemoCentryx Inc. (NASDAQ:CCXI) are each other's competitor in the Biotechnology industry. Thus the contrast of their.
FDA grants priority review to Keytruda for first-line treatment of advanced head and neck cancer - Healio

Posted: February 11th, 2019, 12:26pm GMT

FDA grants priority review to Keytruda for first-line treatment of advanced head and neck cancer Healio
The FDA granted priority review to pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma.
Response durability in Merkel cell CA cases on pembrolizumab | Journal of Clinical Oncology - MD Linx

Posted: February 11th, 2019, 9:27am GMT

Response durability in Merkel cell CA cases on pembrolizumab | Journal of Clinical Oncology MD Linx
Internal Medicine Article: Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line ...
IntelGenx Technologies (IGXT) & OncoSec Medical (ONCS) Head to Head Analysis - Modern Readers

Posted: February 11th, 2019, 9:25am GMT

IntelGenx Technologies (IGXT) & OncoSec Medical (ONCS) Head to Head Analysis Modern Readers
IntelGenx Technologies (OTCMKTS:IGXT) and OncoSec Medical (NASDAQ:ONCS) are both small-cap medical companies, but which is the better investment?
Contrasting of Puma Biotechnology Inc. (PBYI) and Immune Design Corp. (NASDAQ:IMDZ) - The Moveefy

Posted: February 11th, 2019, 9:20am GMT

Contrasting of Puma Biotechnology Inc. (PBYI) and Immune Design Corp. (NASDAQ:IMDZ) The Moveefy
As Biotechnology businesses, Puma Biotechnology Inc. (NASDAQ:PBYI) and Immune Design Corp. (NASDAQ:IMDZ), are affected by contrast. This especially ...
OncoSec Medical (ONCS) vs. IntelGenx Technologies (IGXT) Critical Research - BharataPress

Posted: February 11th, 2019, 9:02am GMT

OncoSec Medical (ONCS) vs. IntelGenx Technologies (IGXT) Critical Research BharataPress
OncoSec Medical (NASDAQ:ONCS) and IntelGenx Technologies (OTCMKTS:IGXT) are both small-cap medical companies, but which is the superior business?
Immunotherapy may be better than chemotherapy for Merkel cell carcinoma - News-Medical.net

Posted: February 11th, 2019, 6:16am GMT

Immunotherapy may be better than chemotherapy for Merkel cell carcinoma News-Medical.net
The first study of the immunotherapy drug pembrolizumab as the initial treatment for patients with a rare but aggressive form of skin cancer known as Merkel cell ...
NantKwest, Inc. (NK) EPS Estimated At $-0.31 | Thorold News - Thorold News

Posted: February 11th, 2019, 4:14am GMT

NantKwest, Inc. (NK) EPS Estimated At $-0.31 | Thorold News Thorold News
Analysts expect NantKwest, Inc. (NASDAQ:NK) to report $-0.31 EPS on March, 11.They anticipate $0.00 EPS change or 0.00 % from last quarter's $-0.31 EPS.
Blackrock Muniholdings California Quality Fund Inc (NYSE:MUC) Big Money Sentiment Is 1.63 - Z Tribune

Posted: February 10th, 2019, 1:33pm GMT

Blackrock Muniholdings California Quality Fund Inc (NYSE:MUC) Big Money Sentiment Is 1.63 Z Tribune
“Big money sentiment for Blackrock Muniholdings California Quality Fund Inc (NYSE:MUC) in Q3 2018 decreased to 1.63, according to SEC filings. So its down ...
Aravive Inc. (ARAV)'s Financial Results Comparing With OncoSec Medical Incorporated (NASDAQ:ONCS) - The FinHeadLines

Posted: February 10th, 2019, 10:13am GMT

Aravive Inc. (ARAV)'s Financial Results Comparing With OncoSec Medical Incorporated (NASDAQ:ONCS) The FinHeadLines
Both Aravive Inc. (NASDAQ:ARAV) and OncoSec Medical Incorporated (NASDAQ:ONCS) compete on a level playing field in the Biotechnology industry. We will ...
Analysts’ Recent Ratings Updates for Immune Design (IMDZ) - Fairfield Current

Posted: February 10th, 2019, 9:30am GMT

Analysts’ Recent Ratings Updates for Immune Design (IMDZ) Fairfield Current
Immune Design (NASDAQ: IMDZ) recently received a number of ratings updates from brokerages and research firms: 1/14/2019 – Immune Design had its “buy” ...
OncoSec Medical (ONCS) vs. IntelGenx Technologies (IGXT) Critical Survey - Fairfield Current

Posted: February 9th, 2019, 9:19am GMT

OncoSec Medical (ONCS) vs. IntelGenx Technologies (IGXT) Critical Survey Fairfield Current
OncoSec Medical (NASDAQ:ONCS) and IntelGenx Technologies (OTCMKTS:IGXT) are both small-cap medical companies, but which is the superior business?
Immune Design Corp. (IMDZ) EPS Estimated At $-0.29; Dril-Quip, Inc. (DRQ) Covered By 0 Bullish Analysts Last Week - The Yomi Blog

Posted: February 8th, 2019, 4:28pm GMT

Immune Design Corp. (IMDZ) EPS Estimated At $-0.29; Dril-Quip, Inc. (DRQ) Covered By 0 Bullish Analysts Last Week The Yomi Blog
Analysts expect Immune Design Corp. (NASDAQ:IMDZ) to report $-0.29 EPS on March, 13.They anticipate $0.00 EPS change or 0.00% from last quarter's $-0.29 ...
Pembrolizumab Improves Survival, Tumor Control in Advanced Merkel Cell Carcinoma - Specialty Pharmacy Times

Posted: February 8th, 2019, 2:35pm GMT

Pembrolizumab Improves Survival, Tumor Control in Advanced Merkel Cell Carcinoma Specialty Pharmacy Times
Pembrolizumab (Keytruda), an immunotherapy, showed durable tumor control and overall survival as a first-line treatment for advanced Merkel cell carcinoma ...
Analysts See $-0.29 EPS for Immune Design Corp. (IMDZ) | Thorold News - Thorold News

Posted: February 8th, 2019, 1:01pm GMT

Analysts See $-0.29 EPS for Immune Design Corp. (IMDZ) | Thorold News Thorold News
Investors sentiment decreased to 1.18 in Q3 2018. Its down 0.77, from 1.95 in 2018Q2. It turned negative, as 10 investors sold Immune Design Corp. shares ...
NantKwest, Inc. (NK) Analysts See $-0.31 EPS on March, 11 - The EN Bulletin

Posted: February 8th, 2019, 11:49am GMT

NantKwest, Inc. (NK) Analysts See $-0.31 EPS on March, 11 The EN Bulletin
On March, 11 NantKwest, Inc. (NASDAQ:NK)'s earnings release is expected by WallStreet, as reported by RTT. Analysts forecast $-0.31 earnings per share, ...
EPS for NantKwest, Inc. (NK) Expected At $-0.31 | Thorold News - Thorold News

Posted: February 8th, 2019, 11:40am GMT

EPS for NantKwest, Inc. (NK) Expected At $-0.31 | Thorold News Thorold News
Analysts expect NantKwest, Inc. (NASDAQ:NK) to report $-0.31 EPS on March, 11.They anticipate $0.00 EPS change or 0.00 % from last quarter's $-0.31 EPS.
Comparison of Puma Biotechnology Inc. (PBYI) and Immune Design Corp. (NASDAQ:IMDZ) - D Minute

Posted: February 8th, 2019, 8:43am GMT

Comparison of Puma Biotechnology Inc. (PBYI) and Immune Design Corp. (NASDAQ:IMDZ) D Minute
Puma Biotechnology Inc. (NASDAQ:PBYI) and Immune Design Corp. (NASDAQ:IMDZ) have been rivals in the Biotechnology for quite some time. Below is a ...
Immunotherapy drug found to be effective in patients with advanced Merkel cell carcinoma - News-Medical.net

Posted: February 8th, 2019, 4:33am GMT

Immunotherapy drug found to be effective in patients with advanced Merkel cell carcinoma News-Medical.net
A multi-center phase II clinical trial investigating pembrolizumab as a first-line and programmed cell death-1 therapy in patients with advanced Merkel cell ...
Neuroendocrine Tumors Market Current Trends and Future Aspect Analysis 2018-2026 - Honest Version

Posted: February 7th, 2019, 5:42pm GMT

Neuroendocrine Tumors Market Current Trends and Future Aspect Analysis 2018-2026 Honest Version
Tumor that arises from specialized body cells, called neuroendocrine cells, is known as neuroendocrine tumor. Neuroendocrine tumor arises from cells that ...
Immunotherapy drug used as first-line therapy for Merkel cell carcinoma improved survival - Medical Xpress

Posted: February 7th, 2019, 3:16pm GMT

Immunotherapy drug used as first-line therapy for Merkel cell carcinoma improved survival Medical Xpress
A multi-center phase II clinical trial investigating pembrolizumab as a first-line and programmed cell death-1 therapy in patients with advanced Merkel cell ...
Immunotherapy drug used as 1st-line therapy for Merkel cell carcinoma improved survival - EurekAlert

Posted: February 7th, 2019, 2:12pm GMT

Immunotherapy drug used as 1st-line therapy for Merkel cell carcinoma improved survival EurekAlert
A multi-center phase II clinical trial investigating pembrolizumab as a first-line and programmed cell death-1 therapy in patients with advanced Merkel cell ...
Metallic woodImmunotherapy for rare skin cancer inspires optimism - ScienceBlog.com

Posted: February 7th, 2019, 12:58pm GMT

Metallic woodImmunotherapy for rare skin cancer inspires optimism ScienceBlog.com
More than two-thirds of people with an advanced form of a rare skin cancer are on track to survive at least two years after starting an immunotherapy drug.
Zealand Pharma A/S (ZEAL) and OncoSec Medical Incorporated (NASDAQ:ONCS) Contrasting side by side - The Yomi Blog

Posted: February 7th, 2019, 12:49pm GMT

Zealand Pharma A/S (ZEAL) and OncoSec Medical Incorporated (NASDAQ:ONCS) Contrasting side by side The Yomi Blog
This is a contrast between Zealand Pharma A/S (NASDAQ:ZEAL) and OncoSec Medical Incorporated (NASDAQ:ONCS) based on their profitability, analyst.
Reviewing NantKwest Inc. (NK)'s and UroGen Pharma Ltd. (NASDAQ:URGN)'s results - EN Digest

Posted: February 7th, 2019, 11:49am GMT

Reviewing NantKwest Inc. (NK)'s and UroGen Pharma Ltd. (NASDAQ:URGN)'s results EN Digest
NantKwest Inc. (NASDAQ:NK) and UroGen Pharma Ltd. (NASDAQ:URGN), are influenced by compare since they are both players in the Biotechnology.
New Jersey Better Educational Savings Trust Decreased Its Disney Walt Co (DIS) Holding; Immune Design (IMDZ) Shorts Down By 38.73% - The Yomi Blog

Posted: February 7th, 2019, 9:52am GMT

New Jersey Better Educational Savings Trust Decreased Its Disney Walt Co (DIS) Holding; Immune Design (IMDZ) Shorts Down By 38.73% The Yomi Blog
New Jersey Better Educational Savings Trust decreased Disney Walt Co (DIS) stake by 40% reported in 2018Q3 SEC filing. New Jersey Better Educational ...
Immune Design Corp. (IMDZ)'s Financial Results Comparing With Sangamo Therapeutics Inc. (NASDAQ:SGMO) - The FinHeadLines

Posted: February 7th, 2019, 4:42am GMT

Immune Design Corp. (IMDZ)'s Financial Results Comparing With Sangamo Therapeutics Inc. (NASDAQ:SGMO) The FinHeadLines
Both Immune Design Corp. (NASDAQ:IMDZ) and Sangamo Therapeutics Inc. (NASDAQ:SGMO) are each other's competitor in the Biotechnology industry.
Regeneron Pharmaceuticals Inc. (REGN)'s Financial Results Comparing With Immune Design Corp. (NASDAQ:IMDZ) - The FinReviewer

Posted: February 7th, 2019, 1:32am GMT

Regeneron Pharmaceuticals Inc. (REGN)'s Financial Results Comparing With Immune Design Corp. (NASDAQ:IMDZ) The FinReviewer
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Immune Design Corp. (NASDAQ:IMDZ) are two firms in the Biotechnology that compete against each ...
Nektar Therapeutics (NKTR) and OncoSec Medical Incorporated (NASDAQ:ONCS) Comparison side by side - The FinExaminer

Posted: February 7th, 2019, 1:16am GMT

Nektar Therapeutics (NKTR) and OncoSec Medical Incorporated (NASDAQ:ONCS) Comparison side by side The FinExaminer
Nektar Therapeutics (NASDAQ:NKTR) and OncoSec Medical Incorporated (NASDAQ:ONCS) compete with each other in the Biotechnology sector. We will ...
Fennec Pharmaceuticals Inc. (FENC) and NantKwest Inc. (NASDAQ:NK) Comparing side by side - D Minute

Posted: February 7th, 2019, 12:39am GMT

Fennec Pharmaceuticals Inc. (FENC) and NantKwest Inc. (NASDAQ:NK) Comparing side by side D Minute
Fennec Pharmaceuticals Inc. (NASDAQ:FENC) and NantKwest Inc. (NASDAQ:NK) have been rivals in the Biotechnology for quite some time. Below is a review ...
Reviewing Avadel Pharmaceuticals plc (AVDL)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results - The Moveefy

Posted: February 7th, 2019, 12:15am GMT

Reviewing Avadel Pharmaceuticals plc (AVDL)'s and OncoSec Medical Incorporated (NASDAQ:ONCS)'s results The Moveefy
Since Avadel Pharmaceuticals plc (NASDAQ:AVDL) and OncoSec Medical Incorporated (NASDAQ:ONCS) are part of the Biotechnology industry, they are ...
ContraVir Pharmaceuticals Inc. (CTRV)'s Financial Results Comparing With OncoSec Medical Incorporated (NASDAQ:ONCS) - The Yomi Blog

Posted: February 7th, 2019, 12:07am GMT

ContraVir Pharmaceuticals Inc. (CTRV)'s Financial Results Comparing With OncoSec Medical Incorporated (NASDAQ:ONCS) The Yomi Blog
Both ContraVir Pharmaceuticals Inc. (NASDAQ:CTRV) and OncoSec Medical Incorporated (NASDAQ:ONCS) are each other's competitor in the Biotechnology ...
NantKwest Inc. (NK)'s Financial Results Comparing With Tiziana Life Sciences PLC (NASDAQ:TLSA) - D Minute

Posted: February 7th, 2019, 11:01pm GMT

NantKwest Inc. (NK)'s Financial Results Comparing With Tiziana Life Sciences PLC (NASDAQ:TLSA) D Minute
This is a contrast between NantKwest Inc. (NASDAQ:NK) and Tiziana Life Sciences PLC (NASDAQ:TLSA) based on their profitability, analyst recommendations, ...
Reviewing ERYTECH Pharma SA (ERYP)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results - The FinReviewer

Posted: February 7th, 2019, 10:30pm GMT

Reviewing ERYTECH Pharma SA (ERYP)'s and Immune Design Corp. (NASDAQ:IMDZ)'s results The FinReviewer
We will be comparing the differences between ERYTECH Pharma S.A. (NASDAQ:ERYP) and Immune Design Corp. (NASDAQ:IMDZ) as far as risk, analyst ...

Trial - Merkel Cell Cancer

FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors

Posted: February 15th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Lymphoma; HER2 Positive; Gastric Cancer; Colorectal Cancer; Head and Neck Cancer; Squamous Cell Carcinoma; EGFR Positive Solid Tumor; HER2-positive Breast Cancer; Hepatocellular Carcinoma; Small Cell Lung Cancer; Renal Cell Carcinoma; Pancreas Cancer; Melanoma; NSCLC; Urothelial Carcinoma; Cervical Cancer; Microsatellite Instability; Merkel Cell Carcinoma
Interventions: Drug: FT500; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Atezolizumab
Sponsor: Fate Therapeutics
Not yet recruiting
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Posted: January 25th, 2019, 3:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; High-Frequency Microsatellite Instability; Metastatic Basal Cell Carcinoma; Metastatic Melanoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Unresectable Melanoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus
Sponsor: National Cancer Institute (NCI)
Not yet recruiting
Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer

Posted: January 10th, 2019, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Radiation: Radiation Therapy
Sponsors: Hiral Shah; National Cancer Institute (NCI)
Recruiting
QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

Posted: July 25th, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Urothelial Carcinoma; Head and Neck Squamous Cell Carcinoma; Merkel Cell Carcinoma; Melanoma; Renal Cell Carcinoma; Gastric Cancer; Cervical Cancer; Hepatocellular Carcinoma; Microsatellite Instability; Mismatch Repair Deficiency; Colorectal Cancer
Interventions: Drug: ALT-803 + Pembrolizumab; Drug: ALT-803 + Nivolumab; Drug: ALT-803 + Atezolizumab; Drug: ALT-803 + Avelumab
Sponsor: Altor BioScience
Recruiting
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Posted: March 6th, 2017, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Skin Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb
Recruiting
A Study of ABBV-181 in Participants With Advanced Solid Tumors

Posted: December 22nd, 2016, 3:00pm GMT

Condition: Advanced Solid Tumors
Interventions: Drug: Rovalpituzumab Tesirine; Drug: ABBV-181
Sponsor: AbbVie
Recruiting
$Permalink for 'Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides'$
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

Posted: September 7th, 2016, 2:00pm GMT

Conditions: Solid Tumors; Mycosis Fungoides; Melanoma; Merkel-cell Carcinoma; Squamous Cell Carcinoma; Breast Carcinoma; Human Papillomavirus-Related Malignant Neoplasm; Soft Tissue Sarcoma
Interventions: Drug: TTI-621 Monotherapy; Drug: TTI-621 + PD-1/PD-L1 Inhibitor; Drug: TTI-621 + pegylated interferon-α2a; Other: TTI-621 + T-Vec; Other: TTI-621 + radiation
Sponsor: Trillium Therapeutics Inc.
Recruiting
Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Posted: June 15th, 2015, 2:00pm GMT

Conditions: Dermatologic Conditions; Healthy Volunteers; Normal Volunteers; Carcinoma, Merkel Cell
Intervention:
Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Recruiting

Trial - Neuroendocrine Cancers

A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma and Pancreatic Neuroendocrine Tumours to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomark

Posted: February 15th, 2019, 3:00pm GMT

Condition: Pancreatic Adenocarcinoma
Intervention:
Sponsor: Royal Marsden NHS Foundation Trust
Recruiting
FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors

Posted: February 15th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Lymphoma; HER2 Positive; Gastric Cancer; Colorectal Cancer; Head and Neck Cancer; Squamous Cell Carcinoma; EGFR Positive Solid Tumor; HER2-positive Breast Cancer; Hepatocellular Carcinoma; Small Cell Lung Cancer; Renal Cell Carcinoma; Pancreas Cancer; Melanoma; NSCLC; Urothelial Carcinoma; Cervical Cancer; Microsatellite Instability; Merkel Cell Carcinoma
Interventions: Drug: FT500; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Atezolizumab
Sponsor: Fate Therapeutics
Not yet recruiting
Second-line Therapy for Patients With Progressive Poorly Differentiated Extra-pulmonary Neuroendocrine Carcinoma

Posted: February 12th, 2019, 3:00pm GMT

Conditions: Oncology; Neuroendocrine Carcinoma
Interventions: Drug: Liposomal Irinotecan; Drug: Fluorouracil; Drug: Folinic Acid; Drug: Docetaxel
Sponsors: Dr Mairéad McNamara; University of Leeds; Servier; National Institute for Health Research, United Kingdom
Recruiting
Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

Posted: February 12th, 2019, 3:00pm GMT

Condition: Medullary Thyroid Cancer
Intervention: Drug: Ponatinib
Sponsors: Antonio Fojo; Millennium Pharmaceuticals, Inc.
Not yet recruiting
Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms

Posted: February 8th, 2019, 3:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Pancreas Neoplasm; Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
Intervention: Device: EUS guided radiofrequency ablation
Sponsor: Catholic University of the Sacred Heart
Not yet recruiting
Chromogranin A as Blood Marker in Cancer Patients

Posted: January 28th, 2019, 3:00pm GMT

Conditions: Gastric Neoplasms; Pancreatic Neoplasms; Small Intestinal Neoplasms; Colorectal Neoplasms
Intervention: Diagnostic Test: BRAHMS CgA II KRYPTOR
Sponsor: Brahms AG
Not yet recruiting
Cushing's Lipodystrophy

Posted: January 28th, 2019, 3:00pm GMT

Condition: Cushing's Syndrome
Intervention: Procedure: Treatment of Cushing's
Sponsors: Columbia University; New York Obesity and Nutrition Research Center
Recruiting
Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Melanoma or Genitourinary Cancer

Posted: January 28th, 2019, 3:00pm GMT

Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Colitis; Diarrhea; Malignant Genitourinary System Neoplasm; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Other: Best Practice; Other: Biospecimen Collection; Procedure: Endoscopic Procedure; Procedure: Fecal Microbiota Transplantation; Biological: Infliximab; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Vedolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Not yet recruiting
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Posted: January 25th, 2019, 3:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; High-Frequency Microsatellite Instability; Metastatic Basal Cell Carcinoma; Metastatic Melanoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Unresectable Melanoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus
Sponsor: National Cancer Institute (NCI)
Not yet recruiting
Recurrence Rates of Type I Gastric Neuroendocrine Tumors Treated With Long-acting Somatostatin Analogs

Posted: January 23rd, 2019, 3:00pm GMT

Condition: Gastric NET
Intervention: Drug: Octreotide
Sponsor: Peking Union Medical College Hospital
Recruiting
Phase 1 Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma

Posted: January 18th, 2019, 3:00pm GMT

Conditions: Metastatic Solid Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Non-small Cell Lung Cancer; Melanoma; Head and Neck Squamous Cell Carcinoma; Gastric Adenocarcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Esophageal Adenocarcinoma
Intervention: Drug: INBRX-105 - PDL1x41BB antibody
Sponsor: Inhibrx, Inc.
Recruiting
Study of Dendritic Cells Pulsed With Tumor Lysate in Advanced Melanoma Dendritic Cells in Advanced Melanoma

Posted: January 14th, 2019, 3:00pm GMT

Condition: Metastatic Melanoma
Intervention: Biological: Dendritic Cells
Sponsors: PrimeVax Immuno-Oncology Inc.; Advocate Lutheran General Hospital
Not yet recruiting
Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer

Posted: January 10th, 2019, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Radiation: Radiation Therapy
Sponsors: Hiral Shah; National Cancer Institute (NCI)
Recruiting
Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Posted: December 6th, 2018, 3:00pm GMT

Conditions: Cancer; Melanoma (Skin); Melanoma, Uveal; Melanoma, Ocular; Bladder Cancer; Mismatch Repair Deficiency; Microsatellite Instability; Non-melanoma Skin Cancer
Interventions: Biological: RP1; Biological: nivolumab
Sponsor: Replimune Inc.
Recruiting
Biomarker Study of Pancreatic Neuroendocrine Tumours

Posted: November 15th, 2018, 3:00pm GMT

Condition: Pancreatic Neuroendocrine Tumor
Interventions: Radiation: 18F-FDG-PET; Radiation: 68Ga-DOTATOC-PET; Radiation: Computed tomography; Other: Core needle biopsy; Other: Phlebotomy
Sponsor: Uppsala University
Recruiting
$Permalink for 'Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin'$
Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Posted: November 9th, 2018, 3:00pm GMT

Conditions: Locally Advanced Digestive System Neuroendocrine Carcinoma; Locally Advanced Pancreatic Neuroendocrine Carcinoma; Metastatic Digestive System Neuroendocrine Carcinoma; Metastatic Pancreatic Neuroendocrine Carcinoma; Refractory Digestive System Neuroendocrine Carcinoma; Refractory Pancreatic Neuroendocrine Carcinoma; Unresectable Digestive System Neuroendocrine Carcinoma; Unresectable Pancreatic Neuroendocrine Carcinoma
Interventions: Drug: Fluorouracil; Drug: Leucovorin; Drug: Liposomal Irinotecan; Procedure: Quality-of-Life Assessment
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI); Ipsen
Not yet recruiting
CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

Posted: November 1st, 2018, 2:00pm GMT

Conditions: Advanced Cutaneous Melanoma of the Extremity; Advanced Sarcoma of the Extremity; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma of the Extremity; Recurrent Sarcoma of the Extremity; Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Intervention: Drug: FACT Complex-targeting Curaxin CBL0137
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI); Incuron
Not yet recruiting
Evaluation of Melatonin Application of Immediate Dental Implant

Posted: October 1st, 2018, 2:00pm GMT

Condition: Immediate Dental Implant
Intervention: Procedure: immediate implant placement
Sponsor: Cairo University
Not yet recruiting
A Study to Test the Effectiveness of ABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

Posted: September 13th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: ABI-009
Sponsors: Robert Ramirez; Aadi, LLC
Recruiting
pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Posted: August 31st, 2018, 2:00pm GMT

Conditions: Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute
Recruiting
Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer

Posted: August 14th, 2018, 2:00pm GMT

Conditions: Thyroid Cancer; Thyroid Cancer, Medullary; Differentiated Thyroid Cancer; Papillary Thyroid Cancer; Follicular Thyroid Cancer; Poorly Differentiated Thyroid Gland Carcinoma
Interventions: Drug: Lenvatinib; Drug: Sorafenib; Drug: Cabozantinib; Drug: Vandetanib
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting
Molecular-Guided Surgery for Pancreatic and GI Neuroendocrine Cancers

Posted: August 9th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Carcinoma of Pancreas; Carcinoid
Intervention: Drug: Gallium Dotatate
Sponsor: University of Alabama at Birmingham
Not yet recruiting
$Permalink for 'A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)'$
A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)

Posted: July 19th, 2018, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Intergroupe Francophone de Cancerologie Thoracique; Federation Francophone de Cancerologie Digestive; GERCOR - Multidisciplinary Oncology Cooperative Group
Recruiting
18FDG PET for Early Identification of Tumor Exhaust for Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Bronchopulmonary Carcinoma or Melanoma

Posted: July 12th, 2018, 2:00pm GMT

Condition: Non-Small Cell Bronchopulmonary Carcinoma or Melanoma
Intervention: Radiation: 18FDG PET
Sponsor: Centre Antoine Lacassagne
Recruiting
Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate

Posted: July 11th, 2018, 2:00pm GMT

Conditions: Bladder Small Cell Neuroendocrine Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Neuroendocrine Neoplasm; Prostate Small Cell Carcinoma; Stage III Bladder Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Ureter Small Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Drug: Etoposide; Biological: Pembrolizumab
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting
AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With Metastatic Well Differentiated Neuroendocrine Neoplasm

Posted: March 5th, 2018, 3:00pm GMT

Conditions: Carcinoid Syndrome; Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm
Interventions: Other: Carbon C 11 Alpha-methyltryptophan; Other: Laboratory Biomarker Analysis; Procedure: Positron Emission Tomography; Drug: Telotristat Etiprate
Sponsors: Barbara Ann Karmanos Cancer Institute; National Cancer Institute (NCI)
Recruiting
The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes

Posted: February 8th, 2018, 3:00pm GMT

Conditions: Autonomic Nervous System Diseases; Sweat Gland Diseases; Diabetic Neuropathy With Neurologic Complication
Interventions: Drug: Liraglutide 6 mg Solution for Injection; Other: Placebo
Sponsor: Eastern Virginia Medical School
Recruiting
Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery

Posted: December 27th, 2017, 3:00pm GMT

Conditions: Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Propranolol Hydrochloride
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Recruiting
A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide

Posted: September 21st, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Octreotide; Drug: LAR Lanreotide; Behavioral: Questionnaires
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting
PET/CT Imaging of uPAR-expression in Patients With Neuroendocrine Tumors Using 68Ga-NOTA-AE105

Posted: September 11th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: One injection of 68Ga-NOTA-AE105; Device: PET/CT
Sponsor: Rigshospitalet, Denmark
Recruiting
PET/CT Imaging of Angiogenesis in Patients With Neuroendocrine Tumors Using 68Ga-NODAGA-E[c(RGDyK)]2

Posted: September 5th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: One injection of 68Ga-NODAGA-E[c(RGDyK)]2; Device: PET/CT
Sponsor: Rigshospitalet, Denmark
Recruiting
QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

Posted: July 25th, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Urothelial Carcinoma; Head and Neck Squamous Cell Carcinoma; Merkel Cell Carcinoma; Melanoma; Renal Cell Carcinoma; Gastric Cancer; Cervical Cancer; Hepatocellular Carcinoma; Microsatellite Instability; Mismatch Repair Deficiency; Colorectal Cancer
Interventions: Drug: ALT-803 + Pembrolizumab; Drug: ALT-803 + Nivolumab; Drug: ALT-803 + Atezolizumab; Drug: ALT-803 + Avelumab
Sponsor: Altor BioScience
Recruiting
To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Posted: July 18th, 2017, 2:00pm GMT

Condition: Gastro-Enteropancreatic Neuroendocrine Tumor
Intervention: Drug: Satoreotide trizoxetan
Sponsor: Ipsen
Recruiting
Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

Posted: July 12th, 2017, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Melanoma; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms; Fibrosarcoma; Infantile Fibrosarcoma; Congenital Mesoblastic Nephroma; Central Nervous System Neoplasms
Intervention: Drug: LOXO-195
Sponsors: Loxo Oncology, Inc.; Bayer
Recruiting
Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma

Posted: June 16th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Pembrolizumab Injection
Sponsors: University of Utah; Merck Sharp & Dohme Corp.
Recruiting
LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

Posted: April 5th, 2017, 2:00pm GMT

Condition: Melanoma
Interventions: Drug: LY3022855; Drug: Vemurafenib; Drug: Cobimetinib
Sponsors: Dana-Farber Cancer Institute; Eli Lilly and Company
Recruiting
Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors

Posted: March 29th, 2017, 2:00pm GMT

Conditions: Neurofibromatosis 2; Vestibular Schwannoma; Meningioma; Ependymoma; Glioma
Intervention: Drug: Selumetinib
Sponsors: Children's Hospital Medical Center, Cincinnati; AstraZeneca
Recruiting
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Posted: March 6th, 2017, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Skin Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb
Recruiting
Phase 2 Study of ONC201 in Neuroendocrine Tumors

Posted: January 27th, 2017, 3:00pm GMT

Conditions: Recurrent Neuroendocrine Tumor; Metastatic Neuroendocrine Tumor
Intervention: Drug: ONC201
Sponsor: Peter Anderson
Recruiting
Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

Posted: November 17th, 2016, 3:00pm GMT

Conditions: Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Recruiting
Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocr

Posted: November 4th, 2016, 2:00pm GMT

Conditions: Well-differentiated Non-functional NET of Thoracic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Pancreatic Origin; Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma
Intervention: Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Recruiting
A Phase II Trial of Ipilimumab and Nivolumab for the Treatment of Rare Cancers

Posted: October 5th, 2016, 2:00pm GMT

Conditions: Gastrointestinal Cancer; Neuroendocrine Tumours; Malignant Female Reproductive System Neoplasm
Interventions: Drug: Ipilimumab; Drug: Nivolumab
Sponsors: Olivia Newton-John Cancer Research Institute; Bristol-Myers Squibb
Recruiting
$Permalink for 'Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides'$
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

Posted: September 7th, 2016, 2:00pm GMT

Conditions: Solid Tumors; Mycosis Fungoides; Melanoma; Merkel-cell Carcinoma; Squamous Cell Carcinoma; Breast Carcinoma; Human Papillomavirus-Related Malignant Neoplasm; Soft Tissue Sarcoma
Interventions: Drug: TTI-621 Monotherapy; Drug: TTI-621 + PD-1/PD-L1 Inhibitor; Drug: TTI-621 + pegylated interferon-α2a; Other: TTI-621 + T-Vec; Other: TTI-621 + radiation
Sponsor: Trillium Therapeutics Inc.
Recruiting
SRS and Nivolumab in Treating Patients With Newly Diagnosed Melanoma Metastases in the Brain or Spine

Posted: March 23rd, 2016, 2:00pm GMT

Conditions: Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Neoplasm in the Spine; Stage IV Skin Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Accuray Incorporated
Recruiting
Efficacy of Rechallenge With Sunitinib in Metastatic Pancreatic Neuroendocrine Tumor Previously Failed to Sunitinib

Posted: March 21st, 2016, 2:00pm GMT

Condition: Pancreatic Neuroendocrine Tumour Metastatic
Intervention: Drug: Sunitinib
Sponsors: Grupo Espanol de Tumores Neuroendocrinos; Pfizer; Apices Soluciones S.L.
Recruiting
An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies

Posted: March 18th, 2016, 2:00pm GMT

Condition: Solid Tumors and Hematologic Malignancy
Interventions: Drug: INCB059872; Drug: all-trans retinoic acid (ATRA); Drug: azacitidine; Drug: nivolumab
Sponsor: Incyte Corporation
Recruiting
Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPSC001 in NETs

Posted: October 30th, 2015, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Satoreotide tetraxetan
Sponsor: Ipsen
Recruiting
PLX3397 Plus Sirolimus in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors

Posted: October 22nd, 2015, 2:00pm GMT

Conditions: Sarcoma; Malignant Peripheral Nerve Sheath Tumors
Interventions: Drug: PLX3397; Drug: Sirolimus
Sponsors: Gulam Manji; Plexxikon
Recruiting
Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

Posted: October 15th, 2015, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Carcinoma, Ductal, Breast; Melanoma; Solid Tumors; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas
Intervention: Drug: Larotrectinib LOXO-101
Sponsors: Bayer; Loxo Oncology, Inc.
Recruiting
Trial of Topotecan With VX-970, an ATR Kinase Inhibitor, in Small Cell Cancers Amd Extrapulmonary Small Cell Cancers

Posted: July 1st, 2015, 2:00pm GMT

Conditions: Carcinoma, Non-Small -Cell Lung; Ovarian Neoplasms; Small Cell Lung Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Neuroendocrine; Extrapulmonary Small Cell Cancer
Interventions: Drug: Topotecan; Drug: VX-970
Sponsor: National Cancer Institute (NCI)
Recruiting
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma

Posted: February 10th, 2015, 3:00pm GMT

Condition: Metastatic Melanoma
Intervention: Biological: Lifileucel
Sponsor: Iovance Biotherapeutics, Inc.
Recruiting
18F-MFBG Imaging for Evaluation of Neuroendocrine Malignancies

Posted: January 28th, 2015, 3:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Radiation: 18F-MFBG (meta-fluoro benzylguanidine); Device: Positron emission tomography (PET) imaging; Other: Blood draws
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma

Posted: August 25th, 2014, 2:00pm GMT

Conditions: BRAF NP_004324.2:p.V600X; Metastatic Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Drug: Dabrafenib; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment; Drug: Trametinib
Sponsor: National Cancer Institute (NCI)
Recruiting
Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1

Posted: August 7th, 2014, 2:00pm GMT

Conditions: Neurofibromatosis; MPNST
Interventions: Procedure: MRI, FDG-PET/CT scans; Drug: [18F]-FLT-PET/CT scans
Sponsor: National Cancer Institute (NCI)
Recruiting
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms

Posted: November 2nd, 2009, 3:00pm GMT

Conditions: Endocrine Tumors; Thyroid Neoplasms; Parathyroid Neoplasms; Adrenal Neoplasm; Neuroblastoma
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting
A Study to Assess PV-10 Chemoablation of Cancer of the Liver

Posted: September 30th, 2009, 2:00pm GMT

Conditions: Cancer Metastatic to the Liver; Hepatocellular Carcinoma; Metastatic Melanoma; Metastatic Ocular Melanoma; Metastatic Uveal Melanoma
Intervention: Drug: PV-10 (10% rose bengal disodium)
Sponsor: Provectus Biopharmaceuticals, Inc.
Recruiting
$Permalink for 'Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma'$
Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma

Posted: April 6th, 2005, 2:00pm GMT

Conditions: Neuroblastoma; Pheochromocytoma
Intervention: Radiation: iobenguane I 131
Sponsors: Memorial Sloan Kettering Cancer Center; National Cancer Institute (NCI)
Recruiting

PubMed - Neuroendocrine Tumor

Evaluating Risks and Benefits of Evolving Systemic Treatments of Neuroendocrine Tumors.

Fetched: February 16th, 2019, 5:00am GMT

Related Articles

Evaluating Risks and Benefits of Evolving Systemic Treatments of Neuroendocrine Tumors.

JAMA Oncol. 2019 Feb 14;:

Authors: Strosberg JR, Al-Toubah T, Cives M

PMID: 30763444 [PubMed - as supplied by publisher]
Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.

Fetched: February 16th, 2019, 5:00am GMT

Related Articles

Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.

JAMA Oncol. 2019 Feb 14;:

Authors: Kaderli RM, Spanjol M, Kollár A, Bütikofer L, Gloy V, Dumont RA, Seiler CA, Christ ER, Radojewski P, Briel M, Walter MA

Abstract
Importance: Multiple therapies are currently available for patients with neuroendocrine tumors (NETs), yet many therapies have not been compared head-to-head within randomized clinical trials (RCTs).
Objective: To assess the relative safety and efficacy of therapies for NETs.
Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials, trial registries, meeting abstracts, and reference lists from January 1, 1947, to March 2, 2018, were searched. Key search terms included neuroendocrine tumors, gastrointestinal neoplasms, therapy, and randomized controlled trial.
Study Selection: Randomized clinical trials comparing 2 or more therapies in patients with NETs (primarily gastrointestinal and pancreatic) were evaluated. Thirty RCTs met the selection criteria.
Data Extraction and Synthesis: Pairs of independent reviewers screened studies, extracted data, and assessed the risk of bias. A network meta-analysis with a frequentist approach was used to compare the efficacy of therapies; the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.
Main Outcomes and Measures: Disease control, progression-free survival, overall survival, adverse events, and quality of life.
Results: The systematic review identified 30 relevant RCTs comprising 3895 patients (48.4% women) assigned to 22 different therapies for NETs. These therapies showed a broad range of risk for serious and nonserious adverse events. The network meta-analyses included 16 RCTs with predominantly a low risk of bias; nevertheless, precision-of-treatment estimates and estimated heterogeneity were limited. The network meta-analysis found 7 therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.35 [95% CI, 0.28-0.45]), everolimus plus somatostatin analogue (HR, 0.35 [95% CI, 0.25-0.51]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.44 [95% CI, 0.26-0.75]), interferon (HR, 0.37 [95% CI, 0.16-0.83]) interferon plus somatostatin analogue (HR, 0.31 [95% CI, 0.13-0.71]), somatostatin analogue (HR, 0.46 [95% CI, 0.33-0.66]) , and sunitinib (HR, 0.42 [95% CI, 0.26-0.67]) and 5 therapies for gastrointestinal NETs: bevacizumab plus somatostatin analogue (HR, 0.22 [95% CI, 0.05-0.99]), everolimus plus somatostatin analogue (HR, 0.31 [95% CI, 0.11-0.90]), interferon plus somatostatin analogue (HR, 0.27 [95% CI, 0.07-0.96]), Lu 177-dotatate plus somatostatin analogue (HR, 0.08 [95% CI, 0.03-0.26], and somatostatin analogues (HR, 0.40 [95% CI, 0.21-0.78]) with higher efficacy than placebo and suggests an overall superiority of combination therapies.
Conclusions and Relevance: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs.

PMID: 30763436 [PubMed - as supplied by publisher]
Multifocal Small Bowel Carcinoid: Evaluation by 68Ga-DOTATATE PET.

Fetched: February 16th, 2019, 5:00am GMT

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Multifocal Small Bowel Carcinoid: Evaluation by 68Ga-DOTATATE PET.

Clin Nucl Med. 2019 Feb 08;:

Authors: Clark M, Nathan M, Broski S

Abstract
Carcinoid is a subtype of neuroendocrine tumor, a rare group of tumors that are known to express somatostatin receptor 2. Ga-DOTATATE is a somatostatin analog that is specific for somatostatin receptor 2 and therefore allows visualization of neuroendocrine tumors. We present 2 cases of primary multifocal small bowel carcinoid evaluated using Ga-DOTATATE PET/CT, along with contrast-enhanced CT corollary findings. Given the increased sensitivity of Ga-DOTATATE PET/CT compared with CT and In-octreotide scintigraphy, we expect multifocal carcinoid to become increasingly recognized.

PMID: 30762820 [PubMed - as supplied by publisher]
Small cell lung cancers made from scratch.

Fetched: February 16th, 2019, 5:00am GMT

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Small cell lung cancers made from scratch.

J Exp Med. 2019 Feb 13;:

Authors: Gazdar AF, Minna JD

Abstract
In this issue of JEM, Chen et al. [https:] describe a new approach for the transformation of human pluripotent embryonic stem cells (hESCs) into neuroendocrine (NE) tumors of the lung closely resembling human small cell lung cancer (SCLC). Another recent study uses a different method to transform fully differentiated normal human cells into high-grade NE tumors (Park et al. 2018. Science [https:] These approaches and their models provide important new resources for developing diagnostic, preventative, and therapeutic approaches for high-grade NE tumors.

PMID: 30760489 [PubMed - as supplied by publisher]
[18F-FDG PET/CT features on paraganglioma of testis with multiple lymph node and lung metastasis: A case report and literature review].

Fetched: February 16th, 2019, 5:00am GMT

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[18F-FDG PET/CT features on paraganglioma of testis with multiple lymph node and lung metastasis: A case report and literature review].

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Oct 28;43(10):1164-1168

Authors: Lü X, Wang Y, Xu P, Dong C, Xiao Z, Jiang Y

Abstract
OBJECTIVE: To determine the clinicopathological and imaging features in 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) for paraganglioma of testis, and to increase the diagnostic accuracy.  Methods: A case of paraganglioma of testis with multiple lymph node and lung metastasis were reported. PET/CT and pathological findings in the case were retrospectively analyzed.  Results: The patient presented with high blood pressure, high level of catecholamine, and urinary vanillylmandelic acid. The patient underwent 18F-FDG PET/CT, which showed the features including the right testis nodule with a star lesion nearby, the right spermatic cord, the lymphadenopathy of bilateral inguinal and retroperitoneum, the posterior basal segment of right lung nodule, and a lot of brown adipose tissues (BAT) in the whole body with intense FDG uptake. 18F-FDG PET/CT showed that the intense FDG uptake of the BAT disappeared after the excision of the right testis and metastasis of paraganglioma.  Conclusion: PET/CT shows great value in localization diagnose, clinical staging and curative evaluation. PET/CT plays a helpful role in revealing the BAT with 18F-DG avidity in the patients with paraganglioma with elevated blood pressure, high level catecholamine, and urinary vanillylmandelic acid.

PMID: 30523240 [PubMed - indexed for MEDLINE]
Ileal schwannoma causing intussusception in an adult.

Fetched: February 16th, 2019, 5:00am GMT

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Ileal schwannoma causing intussusception in an adult.

BMJ Case Rep. 2018 Oct 30;2018:

Authors: Roulston G, Elwan H, Obeid N, Lirosi F

Abstract
Ileal schwannomas are extremely rare tumours. Very few cases have been previously reported. Most cases present with abdominal pain and gastrointestinal bleeding; intussusception is a rare presentation. Due to limitations in imaging modalities, arriving at a diagnosis preoperatively can be challenging. The only reliable method of diagnosis, and treatment, is resection of the tumour, followed by histological and immunohistochemical testing. This report details the rare case of intussusception as the presenting feature of an ileal schwannoma.

PMID: 30381306 [PubMed - indexed for MEDLINE]
An Update Regarding the Molecular Genetics of Melanocytic Neoplasms and the Current Applications of Molecular Genetic Technologies in Their Diagnosis and Treatment.

Fetched: February 16th, 2019, 5:00am GMT

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An Update Regarding the Molecular Genetics of Melanocytic Neoplasms and the Current Applications of Molecular Genetic Technologies in Their Diagnosis and Treatment.

Clin Lab Med. 2018 06;38(2):385-399

Authors: Kiavash K, Bluth MH, Thompson AD

Abstract
Molecular genetic technologies are used to aid in diagnosis and treatment of borderline melanocytic tumors as an adjuvant to the gold standard histopathologic evaluation. A specific set of fluorescence in situ hybridization probes is widely used to aid in diagnosing challenging melanocytic lesions. New melanoma probe cocktails have revealed increased sensitivity and specificity in ambiguous melanocytic cases. Array comparative genomic hybridization is a more complex technology used for the work-up of diagnostically problematic Spitzoid melanocytic proliferations. Cutting-edge technologies, including next-generation sequencing and cell-free nucleic acid analysis, are promising biomarker applications for mutation detection towards personalized patient management.

PMID: 29776637 [PubMed - indexed for MEDLINE]
Epidemiology of skin cancer in the German population: impact of socioeconomic and geographic factors.

Fetched: February 16th, 2019, 5:00am GMT

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Epidemiology of skin cancer in the German population: impact of socioeconomic and geographic factors.

J Eur Acad Dermatol Venereol. 2018 Nov;32(11):1906-1913

Authors: Augustin J, Kis A, Sorbe C, Schäfer I, Augustin M

Abstract
BACKGROUND: Skin cancer being the most common cancer in Germany has shown increasing incidence in the past decade. Since mostly caused by excessive UV exposure, skin cancer is largely related to behaviour. So far, the impact of regional and sociodemographic factors on the development of skin cancer in Germany is unclear.
OBJECTIVES: This study aimed to investigate the association of potential predictive factors with the prevalence of skin cancers in Germany.
METHODS: Nationwide ambulatory care claims data from persons insured in statutory health insurances (SHI) with malignant melanoma (MM, ICD-10 C43) and non-melanocytic skin cancer (NMSC, ICD-10 C44) in the years 2009-2015 were analysed. In addition, sociodemographic population data and satellite-based UV and solar radiation data were associated. Descriptive and multivariate (spatial) statistical analyses (e.g. Bayes' smoothing) were conducted on county level.
RESULTS: Data from 70.1 million insured persons were analysed. Age-standardized prevalences per 100 000 SHI insured persons for MM and NMSC were 284.7 and 1126.9 in 2009 and 378.5 and 1708.2 in 2015. Marked regional variations were observed with prevalences between 32.9% and 51.6%. Multivariate analysis shows among others statistically significant positive correlations between higher income and education, and MM/NMSC prevalence.
CONCLUSION: Prevalence of MM and NMSC in Germany shows spatio-temporal dynamics. Our results demonstrate that regional UV radiation, sunshine hours and sociodemographic factors have significant impact on skin cancer prevalence in Germany. Individual behaviour obviously is a major determinant which should be subject to preventive interventions.

PMID: 29633375 [PubMed - indexed for MEDLINE]
Inverse association for diagnosis of Alzheimer's disease subsequent to both melanoma and non-melanoma skin cancers in a large, urban, single-centre, Midwestern US patient population.

Fetched: February 16th, 2019, 5:00am GMT

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Inverse association for diagnosis of Alzheimer's disease subsequent to both melanoma and non-melanoma skin cancers in a large, urban, single-centre, Midwestern US patient population.

J Eur Acad Dermatol Venereol. 2018 Nov;32(11):1893-1896

Authors: Ibler E, Tran G, Orrell KA, Serrano L, Majewski S, Sable KA, Thiede R, Laumann AE, West DP, Nardone B

Abstract
BACKGROUND: Although literature demonstrates a decreased risk of Alzheimer's disease (AD) in individuals with various cancers, including squamous cell cancers (SCC) and basal cell cancers (BCC) comprising non-melanoma skin cancers (NMSC), there is a paucity of literature to substantiate an association between malignant melanoma (MM) and AD.
OBJECTIVE: The aim of this study was to determine whether an association exists between MM and AD as well as for NMSC and AD.
METHODS: A large urban, Midwestern, US, single-centre, medical record (EMR) data repository was searched between January 2001 and December 2015, to identify all patients at age ≥60 and <89 years with a clinic follow-up of at least 1 year and no diagnosis for AD, MM or NMSC at the time of the study entry. Data collected included age, gender, race and duration of follow-up. MM and NMSC were detected by ICD-9 codes and ICD-10 codes. Incident diagnosis of AD was also detected by ICD-9 and ICD-10 codes. Logistic regression analysis was utilized to obtain crude and adjusted odds ratios (ORs).
RESULTS: Data for a total of 82 925 patients with known race and gender and were detected. After adjusting for confounding factors (race, gender, age, cerebrovascular disease, peripheral vascular disease and diabetes), there was a significant decreased risk of subsequent AD in patients with MM (OR: 0.39; 95% CI: 0.16-0.96; P = 0.042) as well as in patients with BCC (OR: 0.18; 95% CI: 0.08-0.45; P < 0.0001) and for patients with SCC (OR: 0.08; 95% CI: 0.01-0.56; P = 0.013).
CONCLUSION: These findings add to the growing body of evidence for a decreased risk of AD in patients with various cancers and highlight the need for ongoing research to elucidate both neurologic and biologic mechanisms that may underlie this apparent inverse association.

PMID: 29573497 [PubMed - indexed for MEDLINE]
The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex.

Fetched: February 16th, 2019, 5:00am GMT

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The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex.

Hum Mol Genet. 2018 05 15;27(10):1794-1808

Authors: Deng Y, Qin Y, Srikantan S, Luo A, Cheng ZM, Flores SK, Vogel KS, Wang E, Dahia PLM

Abstract
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent. Conversely, both murine and human cells lacking TMEM127 accumulate LAMTOR proteins in the lysosome. Consistent with these findings, pheochromocytomas with TMEM127 mutations have increased levels of LAMTOR proteins. These results suggest that TMEM127 interactions with ragulator and vATPase at the lysosome contribute to restrain mTORC1 signaling in response to amino acids, thus explaining the increased mTORC1 activation seen in TMEM127-deficient tumors.

PMID: 29547888 [PubMed - indexed for MEDLINE]
Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumours treated with depot somatostatin analogs: a cross-sectional study.

Fetched: February 16th, 2019, 5:00am GMT

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Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumours treated with depot somatostatin analogs: a cross-sectional study.

J Eur Acad Dermatol Venereol. 2018 Nov;32(11):1887-1892

Authors: Chicharro P, Paniagua A, Rodríguez-Jiménez P, Ibañes S, Cortina B, Riveiro J, Sampedro-Núñez MÁ, Fraga J, Marazuela M, Daudén E

Abstract
BACKGROUND: The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential.
OBJECTIVE: To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs.
MATERIALS AND METHODS: Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal computed tomography (CT) scans. High resolution and colour Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy.
RESULTS: Twelve patients (five males, seven females) were included (six midgut carcinoid NETs, six pancreatic NETs). Three patients received intramuscular depot octreotide, seven subcutaneous lanreotide, and two both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On colour Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in five patients, revealing a characteristic acellular proteinaceous material. Biopsy in four patients showed different reactional infiltrates around the acellular material.
CONCLUSIONS: High resolution and colour Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.

PMID: 29377286 [PubMed - indexed for MEDLINE]
Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty.

Fetched: February 12th, 2019, 5:00am GMT

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Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty.

Phys Med. 2019 Jan;57:41-46

Authors: Mori M, Benedetti G, Partelli S, Sini C, Andreasi V, Broggi S, Barbera M, Cattaneo GM, Muffatti F, Panzeri M, Falconi M, Fiorino C, De Cobelli F

Abstract
PURPOSE: The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF).
METHODS: Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement.
RESULTS: The median volume was 1.3 cc (range: 0.2-110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48-0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID).
CONCLUSIONS: The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN.

PMID: 30738530 [PubMed - in process]
Bifocal germinoma in a patient with 16p11.2 microdeletion syndrome.

Fetched: February 11th, 2019, 5:00am GMT

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Bifocal germinoma in a patient with 16p11.2 microdeletion syndrome.

Endocrinol Diabetes Metab Case Rep. 2019 Feb 07;2019:

Authors: Ventura M, Gomes L, Rosmaninho-Salgado J, Barros L, Paiva I, Melo M, Oliveira D, Carrilho F

Abstract
Intracranial germinomas are rare tumors affecting mostly patients at young age. Therefore, molecular data on its etiopathogenesis are scarce. We present a clinical case of a male patient of 25 years with an intracranial germinoma and a 16p11.2 microdeletion. His initial complaints were related to obesity, loss of facial hair and polydipsia. He also had a history of social-interaction difficulties during childhood. His blood tests were consistent with hypogonadotropic hypogonadism and secondary adrenal insufficiency, and he had been previously diagnosed with hypothyroidism. He also presented with polyuria and polydipsia and the water deprivation test confirmed the diagnosis of diabetes insipidus. His sellar magnetic resonance imaging (MRI) showed two lesions: one located in the pineal gland and other in the suprasellar region, both with characteristics suggestive of germinoma. Chromosomal microarray analysis was performed due to the association of obesity with social disability, and the result identified a 604 kb 16p11.2 microdeletion. The surgical biopsy confirmed the histological diagnosis of a germinoma. Pharmacological treatment with testosterone, hydrocortisone and desmopressin was started, and the patient underwent radiotherapy (40 Gy divided in 25 fractions). Three months after radiotherapy, a significant decrease in suprasellar and pineal lesions without improvement in pituitary hormonal deficiencies was observed. The patient is currently under follow-up. To the best of our knowledge, we describe the first germinoma in a patient with a 16p11.2 deletion syndrome, raising the question about the impact of this genetic alteration on tumorigenesis and highlighting the need of molecular analysis of germ cell tumors as only little is known about their genetic background. Learning points: Central nervous system germ cell tumors (CNSGTs) are rare intracranial tumors that affect mainly young male patients. They are typically located in the pineal and suprasellar regions and patients frequently present with symptoms of hypopituitarism. The molecular pathology of CNSGTs is unknown, but it has been associated with gain of function of the KIT gene, isochromosome 12p amplification and a low DNA methylation. Germinoma is a radiosensitive tumor whose diagnosis depends on imaging, tumor marker detection, surgical biopsy and cerebrospinal fluid cytology. 16p11.2 microdeletion syndrome is phenotypically characterized by developmental delay, intellectual disability and autism spectrum disorders. Seminoma, cholesteatoma, desmoid tumor, leiomyoma and Wilms tumor have been described in a few patients with 16p11.2 deletion. Bifocal germinoma was identified in this patient with a 16p11.2 microdeletion syndrome, which represents a putative new association not previously reported in the literature.

PMID: 30738016 [PubMed - as supplied by publisher]
[Treatment of neuroendocrine tumors with radio-labeled somatostatin analogues].

Fetched: February 11th, 2019, 5:00am GMT

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[Treatment of neuroendocrine tumors with radio-labeled somatostatin analogues].

Wiad Lek. 2018;71(9):1770-1773

Authors: Bober B, Zaleska M, Kołodziej M, Kowalski Ł, Saracyn M

Abstract
There is a steady increase in the number of neuroendocrine tumors. Although the knowledge about this tumors' biology is increasing, they are still diagnosed in advanced stadium, when surgical treatment is not an option. One of the treatment methods which are available in this group of patients is peptide receptor radionuclide therapy, which should be considered in selected patients. This treatment is usually well tolerated by patients, though severe adverse events may occur, such as myelosuppression or renal failure.

PMID: 30737938 [PubMed - in process]
A Case Report of a Primary Neuroendocrine Tumour of the Proximal Common Bile Duct.

Fetched: February 11th, 2019, 5:00am GMT

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A Case Report of a Primary Neuroendocrine Tumour of the Proximal Common Bile Duct.

J Gastrointest Cancer. 2019 Feb 09;:

Authors: Chaouch MA, Dougaz MW, Ferjaoui W, Gouta EL, Nouira R, Bouasker I, Dziri C

Abstract

PMID: 30737710 [PubMed - as supplied by publisher]
Medical Management of Gastroenteropancreatic Neuroendocrine Tumors: Current Strategies and Future Advances.

Fetched: February 11th, 2019, 5:00am GMT

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Medical Management of Gastroenteropancreatic Neuroendocrine Tumors: Current Strategies and Future Advances.

J Nucl Med. 2019 Feb 08;:

Authors: Mohamed A, Strosberg JR

Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare neoplasms, characterized by a propensity to secrete hormones which cause distinct clinical syndromes. During the past decade, the systemic treatment landscape has improved significantly: new options include everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), sunitinib, an angiogenesis inhibitor, and cytotoxic regimens such as capecitabine and temozolomide. Moreover, the recent approval of the radiolabeled somatostatin analog 177Lutetium(Lu)-dotatate has had a significant impact on management of neuroendocrine malignancies. In this review, we discuss advances in the medical management of GEP-NETs within the context of the larger multidisciplinary approach to these diseases.

PMID: 30737297 [PubMed - as supplied by publisher]
Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells.

Fetched: February 11th, 2019, 5:00am GMT

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Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells.

J Exp Med. 2019 Feb 08;:

Authors: Chen HJ, Poran A, Unni AM, Huang SX, Elemento O, Snoeck HW, Varmus H

Abstract
Cancer models based on cells derived from human embryonic stem cells (hESCs) may reveal why certain constellations of genetic changes drive carcinogenesis in specialized lineages. Here we demonstrate that inhibition of NOTCH signaling induces up to 10% of lung progenitor cells to form pulmonary neuroendocrine cells (PNECs), putative precursors to small cell lung cancers (SCLCs), and we can increase PNECs by reducing levels of retinoblastoma (RB) proteins with inhibitory RNA. Reducing levels of TP53 protein or expressing mutant KRAS or EGFR genes did not induce or expand PNECs, but tumors resembling early-stage SCLC grew in immunodeficient mice after subcutaneous injection of PNEC-containing cultures in which expression of both RB and TP53 was blocked. Single-cell RNA profiles of PNECs are heterogeneous; when RB levels are reduced, the profiles resemble those from early-stage SCLC; and when both RB and TP53 levels are reduced, the transcriptome is enriched with cell cycle-specific RNAs. Our findings suggest that genetic manipulation of hESC-derived pulmonary cells will enable studies of this recalcitrant cancer.

PMID: 30737256 [PubMed - as supplied by publisher]
Efficacy and Safety of Ablative Therapy in the Treatment of Patients with Metastatic Pheochromocytoma and Paraganglioma.

Fetched: February 11th, 2019, 5:00am GMT

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Efficacy and Safety of Ablative Therapy in the Treatment of Patients with Metastatic Pheochromocytoma and Paraganglioma.

Cancers (Basel). 2019 Feb 07;11(2):

Authors: Kohlenberg J, Welch B, Hamidi O, Callstrom M, Morris J, Sprung J, Bancos I, Young W

Abstract
Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. The goals of treatment include palliating symptoms and reducing tumor burden. Little is known about the use of radiofrequency ablation (RFA), cryoablation (CRYO), and percutaneous ethanol injection (PEI) to treat metastatic PPGL. We performed a retrospective study of patients age 17 years and older with metastatic PPGL who were treated with ablative therapy at Mayo Clinic, USA, between June 14, 1999 and November 14, 2017. Our outcomes measures were radiographic response, procedure-related complications, and symptomatic improvement. Thirty-one patients with metastatic PPGL had 123 lesions treated during 42 RFA, 23 CRYO, and 4 PEI procedures. The median duration of follow-up was 60 months (range, 0⁻163 months) for non-deceased patients. Radiographic local control was achieved in 69/80 (86%) lesions. Improvement in metastasis-related pain or symptoms of catecholamine excess was achieved in 12/13 (92%) procedures. Thirty-three (67%) procedures had no known complications. Clavien-Dindo Grade I, II, IV, and V complications occurred after 7 (14%), 7 (14%), 1 (2%), and 1 (2%) of the procedures, respectively. In patients with metastatic PPGL, ablative therapy can effectively achieve local control and palliate symptoms.

PMID: 30736463 [PubMed]
Neuroendocrine Tumor of the Hilar Bile Duct.

Fetched: February 5th, 2019, 5:00am GMT

Neuroendocrine Tumor of the Hilar Bile Duct.

Anticancer Res. 2019 Feb;39(2):903-907

Authors: Umezaki N, Hashimoto D, Yamashita YI, Nakagawa S, Nakao Y, Itoyama R, Yusa T, Yamao T, Okabe H, Imai K, Hayashi H, Chikamoto A, Baba H

Abstract
Neuroendocrine tumors usually develop in the gastrointestinal tract, pancreas, and lung. Therefore, a neuroendocrine tumor of the bile duct is quite rare. We present a 59-year-old-male patient whose preoperative diagnosis was hilar cholangiocarcinoma. One month after embolization of the left branch and anterior branch of the portal vein, he underwent left hepatic trisegmentectomy and extrahepatic bile duct resection. Pathological examination revealed the neuroendocrine tumor in the submucosal layer of the hilar bile duct. Because there was no neuroendocrine tumor in other organs, the tumor was considered a primary neuroendocrine tumor of the hilar bile duct, rather than a liver metastasis from other organs. We also present a review of the English literature regarding neuroendocrine tumors of the bile duct.

PMID: 30711974 [PubMed - in process]
[Microcystic serous cystadenoma: An uncommon neoplasm of pancreas. Report of two cases].

Fetched: February 5th, 2019, 5:00am GMT

[Microcystic serous cystadenoma: An uncommon neoplasm of pancreas. Report of two cases].

Ann Pathol. 2019 Jan 30;:

Authors: Legrand M, Delalande F, Blechet C, Kerdraon R, Saint-Marc O, Michenet P

Abstract
Microcystic variant of serous cystadenoma of the pancreas is a rare neoplasm; essentially located in the body or tail of the pancreas and associated with the von Hippel-Lindau. Often, patients are asymptomatic and the neoplasm is incidentally discovered. Usually radiographic manifestations are characteristic. Histopathological examination revealed uniform clear cuboidal cells; they can be confused with other clear cell neoplasms like renal cell carcinomas, well-differentiated neuroendocrine tumors and solid pseudopapillary tumors of the pancreas. Immunohistochemistry can be help to establish the diagnosis and to remove differential diagnosis. Serous cystadenoma is a benign neoplasm whose prognosis is excellent. We herein report two cases of microcystic serous cystadenomas of the pancreas diagnosed in two asymptomatic women and review analysis in the literature to remind the main features of this lesion and the main differential diagnosis.

PMID: 30711334 [PubMed - as supplied by publisher]
Radiopathological correlation of a von Hippel-Lindau syndrome associated pancreatic neuroendocrine tumour with clear cell features.

Fetched: February 4th, 2019, 5:00am GMT

Radiopathological correlation of a von Hippel-Lindau syndrome associated pancreatic neuroendocrine tumour with clear cell features.

BMJ Case Rep. 2019 Feb 01;12(2):

Authors: Hopp AC, Collins JM, Nguyen CC, Yang M

PMID: 30709893 [PubMed - in process]
Programmed Death Ligand 1 (PD-L1) Status and Tumor-Infiltrating Lymphocytes in Hot Spots of Primary and Liver Metastases in Prostate Cancer With Neuroendocrine Differentiation.

Fetched: February 4th, 2019, 5:00am GMT

Programmed Death Ligand 1 (PD-L1) Status and Tumor-Infiltrating Lymphocytes in Hot Spots of Primary and Liver Metastases in Prostate Cancer With Neuroendocrine Differentiation.

Clin Genitourin Cancer. 2018 Dec 21;:

Authors: von Hardenberg J, Hartmann S, Nitschke K, Worst TS, Ting S, Reis H, Nuhn P, Weis CA, Erben P

Abstract
BACKGROUND: Prostate cancer with neuroendocrine differentiation (NEPCA) shares similarities in tumor biology with small-cell lung cancer. While immunotherapies were successfully tested in small-cell lung cancer, and programmed death ligand 1 (PD-L1) expression arises as an essential predictive biomarker, the local immune status in NEPCA is still poorly described.
PATIENTS AND METHODS: Paraffin-embedded tissue samples of 39 patients (7 adenocarcinomas with neuroendocrine differentiation [ACA NED], 20 small-cell neuroendocrine carcinomas, 2 well-differentiated neuroendocrine tumors of NEPCA, and 10 adenocarcinoma liver metastases) were examined retrospectively by immunohistochemistry of chromogranin A (CGA), CD56, synaptophysin (SYN), CD3, and PD-L1. Laser capture microdissection was used for neuroendocrine hot-spot evaluation for additional real-time reverse transcription-quantitative PCR analysis (PD-L1, CGA, CD56, SYN, GRP, ASCL1, and DLK1).
RESULTS: PD-L1 immunohistochemistry expression in NEPCA was observed by assay E1L3N in 5 (20.8%) of 24 samples, but not by assay 22c3. Gene expression of PD-L1 could be evaluated in 18 (62%) of 29 samples. Nine (69%) of 13 prostate specimens and 2 (40%) of 5 liver metastases were positive for PD-L1. In ACA NED 4 (80%) of 5 and in small-cell neuroendocrine carcinomas 6 (50%) of 12 specimens were positive for PD-L1. Tumor-infiltrating lymphocytes ≥ 10% were observed in 9 (37.5%) of 24 specimens. Low ASCL1 expression was observed in liver metastases.
CONCLUSION: These data identify molecular PD-L1 features in NEPCA. The predictive role of PD-L1 status and tumor-infiltrating lymphocytes in NEPCA remains to be established.

PMID: 30709785 [PubMed - as supplied by publisher]
Malignant paraganglioma presenting as a mandibular metastasis.

Fetched: January 23rd, 2019, 5:01am GMT

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Malignant paraganglioma presenting as a mandibular metastasis.

Head Neck. 2019 Jan 21;:

Authors: Stanek J, Vahidi S, Wilke CT, Khaja SF

Abstract
BACKGROUND: Metastatic paragangliomas are rare neuroendocrine tumors. Bony metastases most commonly occur in the ribs, vertebrae, and pelvis. Few cases of mandibular metastases have been reported.
METHODS: A 75-year-old female presented with a 6-month history of an enlarging mandibular mass. A biopsy was consistent with a paraganglioma.
RESULTS: Staging workup with 18 F-fluorodeoxyglucose positron emission tomography demonstrated 2 hypermetabolic intra-abdominal lesions adjacent to the inferior vena cava. These were confirmed as paraganglioma by biopsy and presumed as the primary lesions. The patient underwent left segmental mandibulectomy and neck dissection with osteocutaneous fibula free tissue reconstruction.
CONCLUSION: A rare case of malignant paraganglioma presenting as a mandibular metastasis is described. Nuclear medicine studies for paraganglioma are reviewed.

PMID: 30664288 [PubMed - as supplied by publisher]
Survivals of patients with surgically treated and High-grade pancreatic neuroendocrine carcinomas: A comparative study between two American Joint Committee on Cancer 8th tumor-node-metastasis staging systems.

Fetched: January 23rd, 2019, 5:01am GMT

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Survivals of patients with surgically treated and High-grade pancreatic neuroendocrine carcinomas: A comparative study between two American Joint Committee on Cancer 8th tumor-node-metastasis staging systems.

Eur J Surg Oncol. 2019 Jan 11;:

Authors: Yang M, Zhang Y, Zeng L, Ke NW, Tan CL, Tian BL, Xiang B, Liu XB

Abstract
BACKGROUND AND OBJECTIVE: We aimed to compare the two new defined tumor-node-metastasis (TNM) systems in the American Joint Committee on Cancer (AJCC) 8th staging manual for overall survival (OS) analysis of G3 pancreatic neuroendocrine carcinomas (p-NECs) that are currently proposed for pancreatic exocrine adenocarcinomas (p-EACs) and G1/G2 pancreatic neuroendocrine tumors (p-NETs), respectively.
METHODS: The data of patients who were surgically treated and histopathologically diagnosed with G3 p-NECs at West China Hospital of Sichuan University from January 2002 to June 2017 were retrospectively analyzed and compared using the two new AJCC staging systems.
RESULTS: Applying the p-EAC AJCC 8th TNM staging system to G3 p-NECs, the estimated 3-year OSs for each stage were 86.7%, 76.0%, 44.5% and 20.7%, respectively (P < 0.001). According to the G1/G2 p-NETs staging system, the estimated OSs at 3 years for each new AJCC stage were 100.0%, 83.6%, 47.1% and 20.7%, respectively (P < 0.001). The system for p-EACs significantly discriminated the survival difference of G3 p-NECs between Stage I and Stage II (P = 0.019), while the other one for G1/G2 p-NETs could not (P = 0.108). The consistent results of Akaike information criteria with Harrell's concordance index indicated that the AJCC 8th staging system for p-EACs was superior when applied to G3 p-NECs for its better prognostic stratification and more accurate prediction ability for OS.
CONCLUSIONS: Our analysis demonstrated that both TNM systems in the AJCC 8th staging manual were prognostic for patients with G3 p-NECs; however, the classification originally applied to p-EACs was superior and supported its use in clinical practice.

PMID: 30661921 [PubMed - as supplied by publisher]
Separation, banking, and quality control of peripheral blood mononuclear cells from whole blood of melanoma patients.

Fetched: January 23rd, 2019, 5:01am GMT

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Separation, banking, and quality control of peripheral blood mononuclear cells from whole blood of melanoma patients.

Cell Tissue Bank. 2018 Dec;19(4):783-790

Authors: Holland M, Cunningham R, Seymour L, Kleinsteuber K, Cunningham A, Patel T, Manos M, Brennick R, Zhou J, Hodi FS, Severgnini M

Abstract
Peripheral blood mononuclear cells (PBMCs) are essential to the study of autoimmune, infectious, parasitic diseases, and cancer. In the rapidly growing field of cancer immunology, cellular phenotyping provides critical information about patient responses to treatments and treatment efficacies. Notably, the evaluation of T cell based therapies relies on the isolation of highly viable CD3+ T cell, CD4+ Helper T cell, and CD8+ Cytotoxic T cell populations before and during patient treatments. Cryopreservation of PBMC populations allows researchers to thaw and characterize clinical samples by flow cytometry, mass cytometry, sequencing, etc. in a high-throughput manner and in batches. Therefore, it is important to separate and bank an abundance of robust circulating immune cells. Here, we report our internal protocols for the high-quality separation, banking, and thawing of clinically relevant PBMC populations. We present quality control data from 11 melanoma patients and characterize their CD3+, CD4+, and CD8+ T cells by 4-color flow cytometry.

PMID: 30377864 [PubMed - indexed for MEDLINE]
Oxidative Stress-Protective and Anti-Melanogenic Effects of Loliolide and Ethanol Extract from Fresh Water Green Algae, Prasiola japonica.

Fetched: January 23rd, 2019, 5:01am GMT

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Oxidative Stress-Protective and Anti-Melanogenic Effects of Loliolide and Ethanol Extract from Fresh Water Green Algae, Prasiola japonica.

Int J Mol Sci. 2018 Sep 18;19(9):

Authors: Park SH, Choi E, Kim S, Kim DS, Kim JH, Chang S, Choi JS, Park KJ, Roh KB, Lee J, Yoo BC, Cho JY

Abstract
Loliolide is a monoterpenoid hydroxylactone found in many algae, including fresh water green algae, Prasiola japonica. To date, loliolide and compounds in P. japonica have not been studied systematically with respect to skin pharmacology. In this study, we investigated oxidative stress-protective and anti-melanogenic effects of loliolide and P. japonica ethanol extract (Pj-EE), known to contain loliolide, in human keratinocyte (HaCaT) cells and mouse melanoma (B16F10) cells. Loliolide suppressed the transcription of genes encoding matrix metalloproteinases (MMPS), which were induced in HaCaT cells by hydrogen peroxide (H₂O₂) treatment. Loliolide and Pj-EE not only reduced the melanin secretion and content in B16F10 cells but also increased the expression of the antioxidant proteins nuclear factor (erythroid-derived 2)-like 2 (NRF2) and heme oxygenase-1 (HO-1) in HaCaT cells subjected to H₂O₂ treatment. Furthermore, loliolide and Pj-EE decreased expression of the anti-melanogenic protein microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells subjected to α-melanocyte-stimulating hormone (α-MSH) treatment. Our findings demonstrate that loliolide and Pj-EE have antioxidant and anti-melanogenic effects on skin.

PMID: 30231594 [PubMed - indexed for MEDLINE]
NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control.

Fetched: January 23rd, 2019, 5:01am GMT

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NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control.

Cell. 2018 02 22;172(5):1022-1037.e14

Authors: Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis e Sousa C

Abstract
Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival. Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1. Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.

PMID: 29429633 [PubMed - indexed for MEDLINE]
Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns.

Fetched: January 23rd, 2019, 5:01am GMT

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Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns.

Sci Rep. 2017 07 14;7(1):5470

Authors: Chen H, Xue L, Wang H, Wang Z, Wu H

Abstract
The great majority of sporadic vestibular schwannomas (VSs) are due to the inactivation of the NF2 gene. In this study, we found age-dependent differences in the clinical parameters of sporadic VSs. Young patients were characterized by progressive tumour behaviours, including earlier onset of initial symptoms, shorter symptom duration and larger tumour size. An increased rate of "two-hits" of both NF2 alleles, usually by mutation and allelic loss, was observed in young cases compared to older, and this correlated with the loss of protein and mRNA expression. In contrast, the tumours with a single mutation (referred to as 'one-hit') exhibited obvious expression levels. Moreover, a mixture of merlin-expressing tumour cells and non-expressing tumour cells was observed in 'one-hit' schwannomas, suggesting that a subset of 'one-hit' tumour cells was present in these tumours. To mimic the growth promoting effects by the second hit, we performed lentivirus-mediated NF2 knockdown in the 'one-hit' schwannoma cultures. Following the loss of NF2 expression, schwannoma cultures demonstrated increased proliferation rates. Above all, we have identified a correlation between the NF2 status and the growth patterns of sporadic VSs. The treatment decision-making, microsurgery or "wait and scan" strategy, should be carried out according to the tumour's genetic background.

PMID: 28710469 [PubMed - indexed for MEDLINE]
Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids.

Fetched: January 23rd, 2019, 5:01am GMT

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Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids.

J Hepatol. 2017 03;66(3):657-659

Authors: Ziemer M, Koukoulioti E, Beyer S, Simon JC, Berg T

PMID: 27908801 [PubMed - indexed for MEDLINE]
Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors.

Fetched: January 21st, 2019, 5:00am GMT

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Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors.

J Gastrointest Surg. 2019 Jan 18;:

Authors: Fisher AV, Lopez-Aguiar AG, Rendell VR, Pokrzywa C, Rocha FG, Kanji ZS, Poultsides GA, Makris EA, Dillhoff ME, Beal EW, Fields RC, Panni RZ, Idrees K, Smith PM, Cho CS, Beems MV, Maithel SK, Winslow ER, Abbott DE, Weber SM

Abstract
INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear.
METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p < 0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort.
RESULTS: In the entire cohort of 287 patients, median follow-up time was 37 months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA > 5x ULN (HR 4.3, p = 0.01), tumor grade 2/3 (HR 3.7, p = 0.01), resection for recurrent disease (HR 6.2, p < 0.01), and tumor size > 4 cm (HR 4.5, p = 0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points.
DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

PMID: 30659439 [PubMed - as supplied by publisher]
Small-Molecule Inhibition of PD-1 Transcription Is an Effective Alternative to Antibody Blockade in Cancer Therapy.

Fetched: January 18th, 2019, 5:00am GMT

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Small-Molecule Inhibition of PD-1 Transcription Is an Effective Alternative to Antibody Blockade in Cancer Therapy.

Cancer Res. 2018 02 01;78(3):706-717

Authors: Taylor A, Rothstein D, Rudd CE

Abstract
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase, GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small-molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PD-L1-blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings. Furthermore, the conditional genetic deletion of GSK-3α/β reduced PD-1 expression on CD8+ T cells and limited B16 pulmonary metastasis to the same degree as PD-1 gene deficiency. In each model, GSK-3i inhibited PD-1 expression on tumor-infiltrating lymphocytes, while increasing Tbx21 (T-bet) transcription, and the expression of CD107a+ (LAMP1) and granzyme B (GZMB) on CD8+ T cells. Finally, the adoptive transfer of T cells treated ex vivo with a GSK-3 inhibitor delayed the onset of EL4 lymphoma growth to a similar extent as anti-PD-1 pretreatment. Overall, our findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer therapy to a similar degree as PD-1-blocking antibodies.Significance: These findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer therapy to a similar degree as PD-1 blocking antibodies, offering a next-generation approach in the design of immunotherapeutic approaches for cancer management. Cancer Res; 78(3); 706-17. ©2017 AACR.

PMID: 29055015 [PubMed - indexed for MEDLINE]
Malignant Phenotypes in Metastatic Melanoma are Governed by SR-BI and its Association with Glycosylation and STAT5 Activation.

Fetched: January 18th, 2019, 5:00am GMT

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Malignant Phenotypes in Metastatic Melanoma are Governed by SR-BI and its Association with Glycosylation and STAT5 Activation.

Mol Cancer Res. 2018 01;16(1):135-146

Authors: Kinslechner K, Schörghofer D, Schütz B, Vallianou M, Wingelhofer B, Mikulits W, Röhrl C, Hengstschläger M, Moriggl R, Stangl H, Mikula M

Abstract
Metastatic melanoma is hallmarked by elevated glycolytic flux and alterations in cholesterol homeostasis. The contribution of cholesterol transporting receptors for the maintenance of a migratory and invasive phenotype is not well defined. Here, the scavenger receptor class B type I (SCARB1/SR-BI), a high-density lipoprotein (HDL) receptor, was identified as an estimator of melanoma progression in patients. We further aimed to identify the SR-BI-controlled gene expression signature and its related cellular phenotypes. On the basis of whole transcriptome analysis, it was found that SR-BI knockdown, but not functional inhibition of its cholesterol-transporting capacity, perturbed the metastasis-associated epithelial-to-mesenchymal transition (EMT) phenotype. Furthermore, SR-BI knockdown was accompanied by decreased migration and invasion of melanoma cells and reduced xenograft tumor growth. STAT5 is an important mediator of the EMT process and loss of SR-BI resulted in decreased glycosylation, reduced DNA binding, and target gene expression of STAT5. When human metastatic melanoma clinical specimens were analyzed for the abundance of SR-BI and STAT5 protein, a positive correlation was found. Finally, a novel SR-BI-regulated gene profile was determined, which discriminates metastatic from nonmetastatic melanoma specimens indicating that SR-BI drives gene expression contributing to growth at metastatic sites. Overall, these results demonstrate that SR-BI is a highly expressed receptor in human metastatic melanoma and is crucial for the maintenance of the metastatic phenotype.Implications: High SR-BI expression in melanoma is linked with increased cellular glycosylation and hence is essential for a metastasis-specific expression signature. Mol Cancer Res; 16(1); 135-46. ©2017 AACR.

PMID: 28974560 [PubMed - indexed for MEDLINE]
β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility.

Fetched: January 18th, 2019, 5:00am GMT

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β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility.

Oncol Res. 2018 Apr 10;26(3):431-444

Authors: Sumardika IW, Youyi C, Kondo E, Inoue Y, Ruma IMW, Murata H, Kinoshita R, Yamamoto KI, Tomida S, Shien K, Sato H, Yamauchi A, Futami J, Putranto EW, Hibino T, Toyooka S, Nishibori M, Sakaguchi M

Abstract
We previously identified novel S100A8/A9 receptors, extracellular matrix metalloproteinase inducer (EMMPRIN), melanoma cell adhesion molecule (MCAM), activated leukocyte cell adhesion molecule (ALCAM), and neuroplastin (NPTN) β, that are critically involved in S100A8/A9-mediated cancer metastasis and inflammation when expressed at high levels. However, little is known about the presence of any cancer-specific mechanism(s) that modifies these receptors, further inducing upregulation at protein levels without any transcriptional regulation. Expression levels of glycosyltransferase-encoding genes were examined by a PCR-based profiling array followed by confirmation with quantitative real-time PCR. Cell migration and invasion were assessed using a Boyden chamber. Western blotting was used to examine the protein level, and the RNA level was examined by Northern blotting. Immunohistochemistry was used to examine the expression pattern of β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) and MCAM in melanoma tissue. We found that GCNT3 is overexpressed in highly metastatic melanomas. Silencing and functional inhibition of GCNT3 greatly suppressed migration and invasion of melanoma cells, resulting in the loss of S100A8/A9 responsiveness. Among the novel S100A8/A9 receptors, GCNT3 favorably glycosylates the MCAM receptor, extending its half-life and leading to further elevation of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 expression is positively correlated to MCAM expression in patients with high-grade melanomas. Collectively, our results showed that GCNT3 is an upstream regulator of MCAM protein and indicate the possibility of a potential molecular target in melanoma therapeutics through abrogation of the S100A8/A9-MCAM axis.

PMID: 28923134 [PubMed - indexed for MEDLINE]
MELANOCYTOMA OR JUXTAPAPILLARY MELANOMA?

Fetched: January 18th, 2019, 5:00am GMT

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MELANOCYTOMA OR JUXTAPAPILLARY MELANOMA?

Retin Cases Brief Rep. 2019 Winter;13(1):15-17

Authors: Baartman BJ, Ahmad B, Srivastava S, Jones S, Singh AD

Abstract
PURPOSE: To report the case of a melanocytoma of the optic disc leading to severe vision loss, raising concern for possible malignant transformation and optic nerve infiltration.
METHODS: Case report.
RESULTS: A 36-year-old Arabic woman presented to an outside facility with severe vision loss and a clinical picture concerning for optic neuritis with central retinal vein occlusion. On referral to the authors' institution 1 month after initial presentation, the vision of the patient was no light perception in the affected eye, and examination revealed the presence of a pigmented lesion adjacent to the nerve. Although standard 3-T magnetic resonance imaging orbits suggested 15 mm of optic nerve involvement, ultrahigh resolution 7-T magnetic resonance imaging was able to detect only 2 mm of optic nerve involvement.
CONCLUSION: Melanocytoma of the optic disc is most often benign and causes few visual symptoms. However, in rare cases it can lead to severe vision loss and raise concern for malignant transformation. A 7-T magnetic resonance imaging provides higher resolution optic nerve images.

PMID: 28060135 [PubMed - indexed for MEDLINE]
TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness.

Fetched: January 18th, 2019, 5:00am GMT

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TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness.

J Exp Clin Cancer Res. 2018 Dec 28;37(1):326

Authors: Rossi S, Cordella M, Tabolacci C, Nassa G, D'Arcangelo D, Senatore C, Pagnotto P, Magliozzi R, Salvati A, Weisz A, Facchiano A, Facchiano F

Abstract
BACKGROUND: Melanoma aggressiveness determines its growth and metastatic potential. This study aimed at identifying new molecular pathways controlling melanoma cell malignancy.
METHODS: Ten metastatic melanoma cell lines were characterized by their proliferation, migration and invasion capabilities. The most representative cells were also characterized by spheroid formation assay, gene- and protein- expression profiling as well as cytokines secretion and the most relevant pathways identified through bioinformatic analysis were tested by in silico transcriptomic validation on datasets generated from biopsies specimens of melanoma patients. Further, matrix metalloproteases (MMPs) activity was tested by zymography assays and TNF-alpha role was validated by anti-TNF cell-treatment.
RESULTS: An aggressiveness score (here named Melanoma AGgressiveness Score: MAGS) was calculated by measuring proliferation, migration, invasion and cell-doubling time in10human melanoma cell lines which were clustered in two distinct groups, according to the corresponding MAGS. SK-MEL-28 and A375 cell lines were selected as representative models for the less and the most aggressive phenotype, respectively. Gene-expression and protein expression data were collected for SK-MEL-28 and A375 cells by Illumina-, multiplex x-MAP-and mass-spectrometry technology. The collected data were subjected to an integrated Ingenuity Pathway Analysis, which highlighted that cytokine/chemokine secretion, as well as Cell-To-Cell Signaling and Interaction functions as well as matrix metalloproteases activity were significantly different in these two cell types. The key role of these pathways was then confirmed by functional validation. TNF role was confirmed by exposing cells to the anti-TNF Infliximab antibody. Upon such treatment melanoma cells aggressiveness was strongly reduced. Metalloproteases activity was assayed, and their role was confirmed by comparing transcriptomic data from cutaneous melanoma patients (n = 45) and benign nevi (n = 18).
CONCLUSIONS: Inflammatory signals such as TNF and MMP-2 activity are key intrinsic players to determine melanoma cells aggressiveness suggesting new venue sin the identification of novel molecular targets with potential therapeutic relevance.

PMID: 30591049 [PubMed - indexed for MEDLINE]
Progression of hearing loss after LINAC-based stereotactic radiotherapy for vestibular schwannoma is associated with cochlear dose, not with pre-treatment hearing level.

Fetched: January 18th, 2019, 5:00am GMT

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Progression of hearing loss after LINAC-based stereotactic radiotherapy for vestibular schwannoma is associated with cochlear dose, not with pre-treatment hearing level.

Radiat Oncol. 2018 Dec 24;13(1):253

Authors: van Linge A, van Os R, Hoekstra N, Heijmen B, Stienstra L, Dallenga A, Wolbers J, Mendez Romero A

Abstract
BACKGROUND: Although stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration.
METHODS: We retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12 Gy, and patients treated with FSRT had received 30 fractions of 1.8 Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD2. Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiation-a measure we use in linear regression-to assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram).
RESULTS: The median follow-up was 36 months for 67 SRS patients and 63 months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes.
CONCLUSIONS: We found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss.

PMID: 30583739 [PubMed - indexed for MEDLINE]
Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules.

Fetched: January 18th, 2019, 5:00am GMT

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Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules.

J Exp Clin Cancer Res. 2018 Oct 05;37(1):245

Authors: Boussadia Z, Lamberti J, Mattei F, Pizzi E, Puglisi R, Zanetti C, Pasquini L, Fratini F, Fantozzi L, Felicetti F, Fecchi K, Raggi C, Sanchez M, D'Atri S, Carè A, Sargiacomo M, Parolini I

Abstract
BACKGROUND: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described.
METHODS: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression.
RESULTS: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases.
CONCLUSIONS: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement.

PMID: 30290833 [PubMed - indexed for MEDLINE]
Vidian Nerve Schwannoma: A Rare Skull-Base Neoplasm Presenting with Ocular Manifestations: A Case Report and Literature Review.

Fetched: January 18th, 2019, 5:00am GMT

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Vidian Nerve Schwannoma: A Rare Skull-Base Neoplasm Presenting with Ocular Manifestations: A Case Report and Literature Review.

Perm J. 2018;22:

Authors: Masroor FA, Gilde J, Liang J

Abstract
INTRODUCTION: Vidian nerve schwannomas are exceedingly rare, with only 7 cases reported since 2006. Patients presenting with ocular symptoms have been reported in only 1 case.
CASE PRESENTATION: A 54-year-old woman presented with a 3-month history of right periorbital pressure, third cranial nerve palsy, and visual field defect. Imaging results showed a right sphenoid skull-base mass with obliteration of the vidian canal that extended into the pterygopalatine fossa. The patient underwent an extended endoscopic resection with pterygopalatine fossa dissection. Pathologic findings demonstrated a schwannoma.
DISCUSSION: A literature review showed that this is the second reported case of a vidian nerve schwannoma presenting with ocular symptoms and that endoscopic resections are becoming the standard of care. Practitioners should be aware that vidian nerve schwannomas can present as a skull-base mass with predominantly ocular symptoms, including vision loss, secondary to mass effect. Consideration should be given to this entity in the setting of typical radiographic and histopathologic characteristics. Endoscopic approaches to resection are safe and have low morbidity.

PMID: 30285912 [PubMed - indexed for MEDLINE]
Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway.

Fetched: January 18th, 2019, 5:00am GMT

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Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway.

J Exp Clin Cancer Res. 2018 Oct 03;37(1):242

Authors: Zhou X, Yan T, Huang C, Xu Z, Wang L, Jiang E, Wang H, Chen Y, Liu K, Shao Z, Shang Z

Abstract
BACKGROUND: Cancer-associated fibroblasts (CAFs) have been widely reported to promote tumor angiogenesis. However, the underlying mechanisms of the proangiogenic switch of CAFs remain poorly understood. This study aims to clarify the mechanisms underlying the proangiogenic switch of CAFs.
METHODS: NIH/3T3 cells were treated with B16 and B16F10-derived exosomes. Then the CAFs markers and proangiogenic factors were detected by RT-PCR and Western blot. CCK-8 assay, transwell migration assay, tube formation assay, and in vivo Matrigel plug assay were conducted to determine the proangiogenic capability of CAFs. Western blot and AG490 were used to investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the proangiogenic switch of CAFs. Bioinformatics analysis, luciferase reporter assay, microRNA mimic and inhibitor, and xenograft models were used to investigate the role of mmu-miR-155-5p (miR-155) in the proangiogenic switch of CAFs.
RESULTS: In this study, we show that melanoma cell-secreted exosomes can induce reprogramming of fibroblasts into CAFs and that exosomal miR-155 can trigger the proangiogenic switch of CAFs. Mechanistically exosomal miR-155 can be delivered into fibroblasts and promote the expression of proangiogenic factors, including vascular endothelial growth factor A (VEGFa), fibroblast growth factor 2 (FGF2), and matrix metalloproteinase 9 (MMP9), by directly targeting suppressor of cytokine signaling 1 (SOCS1). Downregulation of SOCS1 activates JAK2/STAT3 signaling pathway and elevates the expression levels of VEGFa, FGF2, and MMP9 in fibroblasts. Treatment with exosomes containing overexpressed miR-155 can promote angiogenesis, and the reduction of miR-155 in melanoma cell-secreted exosomes alleviates angiogenesis in vitro and in vivo.
CONCLUSIONS: These results demonstrate that by promoting the expression of proangiogenic factors in recipient fibroblasts via SOCS1/JAK2/STAT3 signaling pathway, melanoma cell-secreted exosomal miR-155 can induce the proangiogenic switch of CAFs. Although tumor angiogenesis is modulated by various factors, exosomal miR-155 may be a potential target for controlling melanoma angiogenesis and used to set up novel strategies to treat melanoma.

PMID: 30285793 [PubMed - indexed for MEDLINE]
Antimelanogenic Effects of Polygonum tinctorium Flower Extract from Traditional Jeju Fermentation via Upregulation of Extracellular Signal-Regulated Kinase and Protein Kinase B Activation.

Fetched: January 18th, 2019, 5:00am GMT

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Antimelanogenic Effects of Polygonum tinctorium Flower Extract from Traditional Jeju Fermentation via Upregulation of Extracellular Signal-Regulated Kinase and Protein Kinase B Activation.

Int J Mol Sci. 2018 Sep 24;19(10):

Authors: Chung YC, Ko JH, Kang HK, Kim S, Kang CI, Lee JN, Park SM, Hyun CG

Abstract
This study was carried out to investigate the antimelanogenic effects of a Polygonum tinctorium flower extract obtained using red nuruk, a traditional Jeju barley-based fermentation starter. We also studied the mechanism of action of the P. tinctorium fermented flower extract (PTFFE) in mouse melanoma cells (B16F10). Cells were treated with various concentrations (62.5, 125 and 250 μg/mL) of PTFFE and the results showed that PTFFE significantly decreased the melanin content and tyrosinase activity without being cytotoxic. In addition, PTFFE strongly inhibited the expression of tyrosinase and tyrosinase-related protein 2 by decreasing the expression of the microphthalmia-associated transcription factor, as shown by a western blot assay. Furthermore, PTFFE inhibited melanogenesis via upregulation of the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B, also known as AKT. We also used inhibitors such as PD98059 (a specific ERK inhibitor) or LY294002 (an AKT inhibitor) to determine whether the signaling pathways are involved. High-performance liquid chromatography fingerprinting showed the presence of a quercetin glucoside (isoquercitrin) and quercetin in PTFFE. To test the potential for PTFFE application as a cosmetic material, we also performed a primary skin irritation test on human skin. In this assay, PTFFE did not induce any adverse reactions at the treatment dose. Based on these results, we suggest that PTFFE may be considered a potential antimelanogenesis candidate for topical applications.

PMID: 30249988 [PubMed - indexed for MEDLINE]
RAS at the Golgi antagonizes malignant transformation through PTPRκ-mediated inhibition of ERK activation.

Fetched: January 18th, 2019, 5:00am GMT

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RAS at the Golgi antagonizes malignant transformation through PTPRκ-mediated inhibition of ERK activation.

Nat Commun. 2018 09 05;9(1):3595

Authors: Casar B, Badrock AP, Jiménez I, Arozarena I, Colón-Bolea P, Lorenzo-Martín LF, Barinaga-Rementería I, Barriuso J, Cappitelli V, Donoghue DJ, Bustelo XR, Hurlstone A, Crespo P

Abstract
RAS GTPases are frequently mutated in human cancer. H- and NRAS isoforms are distributed over both plasma-membrane and endomembranes, including the Golgi complex, but how this organizational context contributes to cellular transformation is unknown. Here we show that RAS at the Golgi is selectively activated by apoptogenic stimuli and antagonizes cell survival by suppressing ERK activity through the induction of PTPRκ, which targets CRAF for dephosphorylation. Consistently, in contrast to what occurs at the plasma-membrane, RAS at the Golgi cannot induce melanoma in zebrafish. Inactivation of PTPRκ, which occurs frequently in human melanoma, often coincident with TP53 inactivation, accelerates RAS-ERK pathway-driven melanomagenesis in zebrafish. Likewise, tp53 disruption in zebrafish facilitates oncogenesis driven by RAS from the Golgi complex. Thus, RAS oncogenic potential is strictly dependent on its sublocalization, with Golgi complex-located RAS antagonizing tumor development.

PMID: 30185827 [PubMed - indexed for MEDLINE]
Multiple cranial nerve schwannomas and meningiomas as a hallmark sign of neurofibromatosis type 2 in a child.

Fetched: January 18th, 2019, 5:00am GMT

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Multiple cranial nerve schwannomas and meningiomas as a hallmark sign of neurofibromatosis type 2 in a child.

Turk J Pediatr. 2018;60(1):107-110

Authors: Halefoğlu AM

Abstract
Halefoğlu AM. Multiple cranial nerve schwannomas and meningiomas as a hallmark sign of neurofibromatosis type 2 in a child. Turk J Pediatr 2018; 60: 107-110. Neurofibromatosis type 2 is a rarely encountered autosomal dominant disorder manifesting with typical radiological findings. These patients have a predilection for development of benign tumors in the central nervous system. Although the presenting symptom is most commonly hearing loss due to acoustic schwannomas, symptoms emanating from other cranial tumors are not uncommon. Herein, we described a 16-year-old male patient presented with multiple meningiomas and cranial nerve schwannomas revealed by magnetic resonance imaging. He fulfilled the diagnostic criteria of neurofibromatosis type 2 and underwent treatment. We emphasized the role of radiology in the early diagnosis of this inherited disorder in order to provide a better prognosis.

PMID: 30102490 [PubMed - indexed for MEDLINE]
Sudden-onset C8 Radiculopathy due to a Plexiform Schwannoma of the Cervical Nerve Root.

Fetched: January 18th, 2019, 5:00am GMT

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Sudden-onset C8 Radiculopathy due to a Plexiform Schwannoma of the Cervical Nerve Root.

Intern Med. 2018 Nov 15;57(22):3317-3320

Authors: Komatsu K, Toda H, Matsumoto S

Abstract
Plexiform schwannoma is a rare variant of schwannomas and usually presents with chronic symptoms. We herein report a case of cervical nerve plexiform schwannoma that presented with unusually sudden severe left radiculopathy of the eighth cervical nerve after physical exercise. Coronal short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) revealed a multinodular tumor along the eighth cervical nerve. The tumor was partially resected. A pathological analysis revealed that the tumor was a schwannoma, and we diagnosed the case as a plexiform schwannoma. The unusual sudden-onset presentation in this case was considered to be caused by the unusual localization of the tumor involving the nerve root and mechanical stress due to physical exercise.

PMID: 29984772 [PubMed - indexed for MEDLINE]
Over-diagnosis of potential malignant behavior in MEN 2A-associated pheochromocytomas using the PASS and GAPP algorithms.

Fetched: January 18th, 2019, 5:00am GMT

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Over-diagnosis of potential malignant behavior in MEN 2A-associated pheochromocytomas using the PASS and GAPP algorithms.

Langenbecks Arch Surg. 2018 Sep;403(6):785-790

Authors: Stenman A, Zedenius J, Juhlin CC

Abstract
PURPOSE: Pheochromocytomas (PCCs) exhibit malignant potential, but current histological modalities for the proper detection of aggressive behavior are debated. The two most widespread algorithms are the "Pheochromocytoma of the Adrenal Gland Scaled Score" (PASS) and the "Grading System for Adrenal Pheochromocytoma and Paraganglioma" (GAPP), both which mostly rely on histological parameters to identify PCC patients at risk of disseminated disease. Since the algorithms are derived from studies using predominantly sporadic PCCs, little is known whether the PASS or GAPP scores can predict malignant potential in hereditary cases.
METHODS: PASS and GAPP were applied on 41 PCCs; 13 PCCs were diagnosed in ten multiple endocrine neoplasia type 2A (MEN 2A) patients carrying established germline RET proto-oncogene mutations, as well as 28 assumed sporadic PCCs.
RESULTS: Six out of thirteen MEN 2A tumors (46%) exhibited PASS scores ≥ 4, indicative of a potential for aggressive behavior. In addition, 7/13 tumors (54%) exhibited GAPP scores ≥ 3, indicative of a "moderately differentiated type" with risk of future recurrence. All MEN 2A PCCs with an elevated PASS score also displayed an elevated GAPP score. In contrast, 4/28 (14%) sporadic PCCs demonstrated PASS scores ≥ 4, and 9/28 (32%) displayed GAPP scores ≥ 3. Follow-up found all cases in the study are free of metastatic or recurrent disease.
CONCLUSIONS: We conclude that the PASS and GAPP scoring systems might be suboptimal for determining true malignant potential in PCCs with constitutional RET mutations and advocate restrictive use of these scores in MEN 2A cases until the results are reproduced in larger numbers.

PMID: 29779047 [PubMed - indexed for MEDLINE]
Loss of miR-204 expression is a key event in melanoma.

Fetched: January 18th, 2019, 5:00am GMT

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Loss of miR-204 expression is a key event in melanoma.

Mol Cancer. 2018 03 09;17(1):71

Authors: Galasso M, Morrison C, Minotti L, Corrà F, Zerbinati C, Agnoletto C, Baldassari F, Fassan M, Bartolazzi A, Vecchione A, Nuovo GJ, Di Leva G, D'Atri S, Alvino E, Previati M, Nickoloff BJ, Croce CM, Volinia S

Abstract
Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds - 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS.

PMID: 29523154 [PubMed - indexed for MEDLINE]
Isolation of Endogenous Peptides from Cultured Cell Conditioned Media for Mass Spectrometry.

Fetched: January 18th, 2019, 5:00am GMT

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Isolation of Endogenous Peptides from Cultured Cell Conditioned Media for Mass Spectrometry.

Methods Mol Biol. 2018;1719:51-58

Authors: Sasaki K, Tsuchiya T, Osaki T

Abstract
Media conditioned by cultured cells represent an excellent source rich in endogenous peptides. Unbiased mass spectrometric analysis of the constituent peptides provides an opportunity to look into proteolytic events such as bioactive peptide processing, membrane protein ectodomain shedding, or even regulated intramembrane proteolysis. If conducted on a large scale, peptidomics has the potential to pinpoint primary cleavage sites. Here a method is described for isolating peptides from cultured cell conditioned media before mass spectrometry analysis.

PMID: 29476503 [PubMed - indexed for MEDLINE]
Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype.

Fetched: January 18th, 2019, 5:00am GMT

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Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype.

Mol Cancer. 2018 02 17;17(1):59

Authors: Sinnberg T, Levesque MP, Krochmann J, Cheng PF, Ikenberg K, Meraz-Torres F, Niessner H, Garbe C, Busch C

Abstract
BACKGROUND: During embryonic development Wnt family members and bone morphogenetic proteins (BMPs) cooperatively induce epithelial-mesenchymal transition (EMT) in the neural crest. Wnt and BMPs are reactivated during malignant transformation in melanoma. We previously demonstrated that the BMP-antagonist noggin blocked the EMT phenotype of melanoma cells in the neural crest and malignant invasion of melanoma cells in the chick embryo; vice-versa, malignant invasion was induced in human melanocytes in vivo by pre-treatment with BMP-2.
RESULTS: Although there are conflicting results in the literature about the role of β-catenin for invasion of melanoma cells, we found Wnt/β-catenin signaling to be analogously important for the EMT-like phenotype of human metastatic melanoma cells in the neural crest and during invasion: β-catenin was frequently expressed at the invasive front of human primary melanomas and Wnt3a expression was inversely correlated with survival of melanoma patients. Accordingly, cytoplasmic β-catenin levels were increased during invasion of melanoma cells in the rhombencephalon of the chick embryo. Fibroblast derived Wnt3a reduced melanoma cell adhesion and enhanced migration, while the β-catenin inhibitor PKF115-584 increased adhesion and reduced migration in vitro and in the chick embryonic neural crest environment in vivo. Similarly, knockdown of β-catenin impaired intradermal melanoma cell invasion and PKF115-584 efficiently reduced liver metastasis in a chick chorioallantoic membrane model. Our observations were accompanied by specific alterations in gene expression which are linked to overall survival of melanoma patients.
CONCLUSION: We present a novel role for Wnt-signaling in neural crest like melanoma cell invasion and metastasis, stressing the crucial role of embryonic EMT-inducing neural crest signaling for the spreading of malignant melanoma.

PMID: 29454361 [PubMed - indexed for MEDLINE]
Quadruple Valve Replacement for Carcinoid Heart Disease.

Fetched: January 17th, 2019, 5:01am GMT

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Quadruple Valve Replacement for Carcinoid Heart Disease.

Braz J Cardiovasc Surg. 2018 Jul-Aug;33(4):398-403

Authors: Mujtaba SS, Clark S

Abstract
INTRODUCTION: Carcinoid heart disease most frequently involves the tricuspid or, more rarely, the pulmonary valve and presents with right heart failure as 5-HT is metabolized by the lung. Left-sided valve involvement is quite rare. We describe our experience of 3 patients presenting with heart failure secondary to carcinoid heart disease affecting all four cardiac valves. There are only four previous isolated case reports in the literature.
METHODS: All three patients underwent quadruple valve replacement during a single operation. Right ventricular outflow tract reconstruction with a pericardial patch was performed in all patients. For 24 hours prior to surgery, all patients received intravenous octreotide, which continued in intensive care for at least 24 hours.
RESULTS: Mean cross-clamp and bypass times were 175 (range 164-197 minutes) and 210 (range 195-229 minutes) minutes, respectively. Mean intensive treatment unit (ITU) and inpatient stays were 2.3 (range 2-3 days) and 12 (range 9-16 days) days, respectively. One patient was reopened for bleeding 4 hours postoperatively from a ventricular pacing wire site. None required a permanent pacemaker postoperatively. There were no other complications in any patient. The quality of life was excellent at 6-16 months clinic follow-up as they were in NYHA 1. Postoperative echocardiography showed no paravalvular leaks and well-functioning prostheses in all cases.
CONCLUSION: Surgery to replace all four valves is feasible with excellent medium-term survival and a very low rate of complications. Patients with carcinoid heart disease should always be considered for surgery irrespective of the extent of valvular involvement.

PMID: 30184038 [PubMed - indexed for MEDLINE]
Combination therapy of tumor-targeting Salmonella typhimurium A1-R and oral recombinant methioninase regresses a BRAF-V600E-negative melanoma.

Fetched: January 17th, 2019, 5:01am GMT

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Combination therapy of tumor-targeting Salmonella typhimurium A1-R and oral recombinant methioninase regresses a BRAF-V600E-negative melanoma.

Biochem Biophys Res Commun. 2018 09 18;503(4):3086-3092

Authors: Kawaguchi K, Higuchi T, Li S, Han Q, Tan Y, Igarashi K, Zhao M, Miyake K, Kiyuna T, Miyake M, Ohshiro H, Sugisawa N, Zhang Z, Razmjooei S, Wangsiricharoen S, Chmielowski B, Nelson SD, Russell TA, Dry SM, Li Y, Eckardt MA, Singh AS, Singh SR, Eilber FC, Unno M, Hoffman RM

Abstract
Melanoma is a recalcitrant cancer. To improve and individualize treatment for this disease, we previously developed a patient-derived orthotopic xenograft (PDOX) model for melanoma. We previously reported the individual efficacy of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and recombinant methioninase (rMETase) for melanoma in the PDOX models of this disease. In the present study, we evaluated the efficacy of the combination of S. typhimurium A1-R with orally-administered rMETase (o-rMETase) for BRAF-V600E-negative melanoma in a PDOX model. Three weeks after implantation, 60 PDOX mouse models were randomized into six groups of 10 mice each: untreated control, temozolomide (TEM); o-rMETase; S. typhimurium A1-R; TEM + rMETase, S. typhimurium A1-R + rMETase. All treatments inhibited tumor growth compared to untreated control (TEM: p < 0.0001, rMETase: p < 0.0001, S. typhimurium A1-R: p < 0.0001, TEM + rMETase: p < 0.0001, S. typhimurium A1-R + rMETase: p < 0.0001). The most effective was the combination of S. typhimurium A1-R + o-rMETase which regressed this melanoma PDOX, thereby indicating a new paradigm for treatment of metastatic melanoma.

PMID: 30166061 [PubMed - indexed for MEDLINE]
Primary malignant melanoma of urethra mimicking as urethral caruncle.

Fetched: January 17th, 2019, 5:01am GMT

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Primary malignant melanoma of urethra mimicking as urethral caruncle.

BMJ Case Rep. 2018 Jul 30;2018:

Authors: Bansal N, Garg G, Vashist S

PMID: 30065058 [PubMed - indexed for MEDLINE]
Mouse models of cancer-induced cachexia: Hind limb muscle mass and evoked force as readouts.

Fetched: January 17th, 2019, 5:01am GMT

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Mouse models of cancer-induced cachexia: Hind limb muscle mass and evoked force as readouts.

Biochem Biophys Res Commun. 2018 09 18;503(4):2415-2420

Authors: Jourdain M, Melly S, Summermatter S, Hatakeyama S

Abstract
The majority of patients with advanced cancer suffer from cachexia, a systemic wasting syndrome, which subsequently impacts the tolerance to anti-cancer treatments, response to therapy, quality of life, and eventually, survival. Despite a high unmet medical need, there is currently no specific remedy available for an effective treatment of cachexia and its sequelae. A key feature of cachexia is the inexorable loss of skeletal muscle mass, which constitutes a main contributor to body weight loss and progressive functional impairments. Therefore, it's crucial to identify early readouts to detect and monitor the loss of muscle mass and function to initiate appropriate treatments timely. Here, we describe experimental cancer models using mouse (syngeneic) or human (xenograft) cancer cell lines with a rapid onset of tumor growth and cachexia. These models are easier to establish, monitor and reproduce compared to the genetically engineered mouse models currently available. Moreover, we establish readouts such as hind limb muscle mass and volume, as well as evoked force and food intake measurements, to allow the evaluation of potential therapeutic agents for the early treatment of cachexia and associated impairments.

PMID: 29969629 [PubMed - indexed for MEDLINE]
The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway.

Fetched: January 17th, 2019, 5:01am GMT

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The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway.

Biochem Biophys Res Commun. 2018 09 18;503(4):2451-2458

Authors: Zheng Y, Sun Y, Liu Y, Zhang X, Li F, Li L, Wang J

Abstract
MicroRNAs were thought to play a regulatory role through complementarity to target messenger RNA (mRNA). Our previous study revealed a miR-31-SOX10 axis that regulated tumor growth and resistance to chemotherapy of melanoma. Up-regulation of SOX10 and down-regulation of miR-31 were found in melanoma tissues. SOX10 was further identified as a target of miR-31. Overexpression of SOX10 dramatically promoted melanoma cell proliferation and chemotherapy resistance both in vitro and in vivo. While enforced miR-31 expression suppressed cell growth and enhanced the chemosensitivity of melanoma cells, the re-expression of SOX10 rescued these effects by activating PI3K/AKT signaling pathway. In conclusion, our results demonstrated that SOX10 acted as an oncogene and was negatively regulated by miR-31, which supports the potential therapeutic strategy against melanoma by targeting the miR-31-SOX10 axis.

PMID: 29969627 [PubMed - indexed for MEDLINE]
Inferior outcomes in immunocompromised Merkel cell carcinoma patients: Can they be overcome by the use of PD1/PDL1 inhibitors?

Fetched: January 17th, 2019, 5:01am GMT

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Inferior outcomes in immunocompromised Merkel cell carcinoma patients: Can they be overcome by the use of PD1/PDL1 inhibitors?

J Oncol Pharm Pract. 2019 Jan;25(1):214-216

Authors: Dasanu CA, Del Rosario M, Codreanu I, Hyams DM, Plaxe SC

Abstract
Cases of Merkel cell carcinoma have become increasingly more common in the last two decades, and its incidence has been predicted to climb further. Immunosenescence might explain in part the higher Merkel cell carcinoma prevalence in seniors aged 70 and older. This cancer might also be more aggressive in immunocompromised patients. In a subset of immunocompromised Merkel cell carcinoma patients, we identified significant lymphopenia and a more advanced disease stage compared with their immunocompetent counterparts. Time to death in this cohort was much shorter than in immunocompetent subjects, and their likelihood of death from Merkel cell carcinoma was five times higher. Avelumab approval in 2017 represents an important step forward in the therapy of Merkel cell carcinoma. Hopefully, PD1/PDL1 inhibitors will improve survival in immunocompromised Merkel cell carcinoma hosts, traditionally linked with inferior clinical outcomes.

PMID: 29933728 [PubMed - indexed for MEDLINE]
[Catecholamine Cardiomyopathy Presenting Inverted-takotsubo Pattern Asynergy].

Fetched: January 17th, 2019, 5:01am GMT

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[Catecholamine Cardiomyopathy Presenting Inverted-takotsubo Pattern Asynergy].

Masui. 2017 Apr;66(4):401-404

Authors: Okuno T, Hino M, Kiyama R, Shindo K

Abstract
Pheochromocytoma is complicated with catecholamine cardiomyopathy, and preoperative care becomes considerably more difficult We report anesthetic management for an 48-year-old man brought to our hospital by ambulance and immediately hospitalized due to pheochromocytoma crisis complicated with catechol- amine cardiomyopathy presenting inverted-takotsubo pattern asynergy. Before surgery, α and β blocking drugs were used to control hypertension and tachycardia, and continuous hemodiafiltration was initiated and the patient was intubated for severe pulmonary edema. Seven days later, he underwent laparoscopic adrenalectomy. Total intravenous anesthesia was achieved with propofol, remifentanil, fentanyl, and rocuronium. During the operation, continuous infusion of landiolol, phentolamine, and nitroglycerin, and addi- tional bolus injections of landiolol were given to control hypertension. After severing the right adrenal vein, noradrenaline (0.15 μg · kg⁻¹ · min⁻¹), and dopamine (4μg · kg⁻¹ · min⁻¹) were started and the patient was placed in the intensive care unit Inverted-takotsubo pattern asynergy is not very common, and treatment consists of supportive care, as in the usual takotsubo. Preoperative CHDF (continuous hemodiafiltration) may be useful when it is difficult to control hypertension or tachycardia with medications.

PMID: 30382641 [PubMed - indexed for MEDLINE]
Human Papillomavirus T-Cell Cross-reactivity in Cervical Cancer: Implications for Immunotherapy Clinical Trial Design.

Fetched: January 17th, 2019, 5:01am GMT

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Human Papillomavirus T-Cell Cross-reactivity in Cervical Cancer: Implications for Immunotherapy Clinical Trial Design.

JAMA Netw Open. 2018 Jul 06;1(3):e180706

Authors: Helman SR, Stevanovic S, Campbell TE, Kwong MLM, Doran SL, Faquin WC, Hinrichs CS

Abstract
Importance: Clinical trials are testing vaccines that target human papillomavirus 16 (HPV-16) oncoproteins for the treatment of cervical cancer regardless of the HPV type of the tumor. For patients with HPV-18-positive cancers, this strategy relies on cross-reactivity of HPV-16-reactive T cells against the HPV-18 oncoproteins.
Objectives: To determine the prevalence of HPV-16 and HPV-18 metastatic cervical cancers in women enrolling in clinical trials at a US medical center and to assess whether HPV oncoprotein-targeting tumor-infiltrating lymphocytes (TILs) and T-cell receptors (TCRs) possess HPV-16/HPV-18 oncoprotein cross-reactivity.
Design, Setting, and Participants: This study was conducted at the National Institutes of Health Clinical Center, a tertiary care research hospital in the United States. The HPV type of the tumors from 65 consecutive patients with cervical cancer who were evaluated for participation in clinical trials was determined by retrospective medical record review. Immunological assays testing HPV cross-reactivity were conducted on all available archived samples of oncoprotein-reactive TILs from HPV-positive tumors (n = 16) and on a library of previously identified TCRs (n = 10).
Interventions: The HPV genotype of each patient's tumor was determined. The cross-reactivity of archived TILs and a library of TCRs was assessed.
Main Outcomes and Measures: The main outcomes were the prevalence of each HPV genotype and the frequency of TILs or TCRs with HPV oncoprotein-T-cell cross-reactivity. Cross-reactivity was assessed by enzyme-linked immunospot assays and interferon-γ production assays.
Results: The median (range) age of 65 referred patients was 44 (24-64) years. Ethnicity was recorded for 39 of 65 patients; 35 (89.7%) were white, 3 (7.7%) were Asian, and 1 (2.6%) was American Indian/Alaskan Native. Histologic tumor subtype was recorded for 41 of 65 patients; 25 (61.0%) were squamous cell carcinomas, 12 (29.3%) were adenocarcinomas, 2 (4.9%) were adenosquamous cell carcinomas, and 2 (4.9%) were neuroendocrine tumors. Thirty-nine of 65 patients (60.0%) had HPV-16-positive tumors and 21 patients (32.3%) had HPV-18-positive tumors. In the analysis of cross-reactivity, 1 of 16 oncoprotein-reactive archived TILs (9 from cervical cancers and 7 from other cancers) displayed HPV-16/HPV-18 cross-reactivity. None of the 10 oncoprotein-reactive TCRs displayed HPV-16/HPV-18 cross-reactivity.
Conclusions and Relevance: Cervical cancers that tested positive for HPV-18 were common in this study and may be common in other US clinical trial populations. Results showed that HPV-16/HPV-18 intergenotype T-cell cross-reactivity of T cells from HPV-16-positive and HPV-18-positive cancers was uncommon. These findings support clinical trial designs in which the HPV type targeted by a therapeutic vaccine is matched with the HPV type of a cancer and suggest a change is necessary in the design of active clinical trials.

PMID: 30646017 [PubMed - in process]
Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Fetched: January 17th, 2019, 5:01am GMT

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Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Onco Targets Ther. 2019;12:319-339

Authors: Papanagnou P, Papadopoulos GE, Stivarou T, Pappas A

Abstract
Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic use of octreotide is restricted primarily to the management of acromegaly and neuroendocrine tumors, both of which are rare medical conditions. Similarly, chloroquine is used mainly for the treatment of malaria, which is designated as a rare disease in Western countries. This limited exploitation contradicts the experimental findings of numerous studies outlining the possible expansion of the use of octreotide to include the treatment of common human malignancies and the repositioning of chloroquine in oncology. Herein, we review the current knowledge on the antitumor function of these two agents stemming from preclinical or clinical experimentation. In addition, we present in silico evidence on octreotide potentially binding to multiple Wnt-pathway components. This will hopefully aid in the design of new efficacious anticancer therapeutic regimens with minimal toxicity, which represents an enormous unmet demand in oncology.

PMID: 30643430 [PubMed]
Large cell neuroendocrine carcinoma of the uterine cervix.

Fetched: January 17th, 2019, 5:01am GMT

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Large cell neuroendocrine carcinoma of the uterine cervix.

BMJ Case Rep. 2019 Jan 14;12(1):

Authors: Habeeb A, Habeeb H

Abstract
We report a case of large cell neuroendocrine carcinoma of the uterine cervix. A 33-year-old woman presented with a 4-month history of irregular vaginal bleeding and suspicious cervix. Transvaginal ultrasound showed a 3×3.8 cm cervical mass with a marked increase in the blood flow. MRI pelvis showed an exophytic tumour with left external iliac lymph node metastasis. Immunohistochemistry of the tumour cells showed strong positivity for the neuroendocrine markers synaptophysin and a very high Ki67 proliferation index. A diagnosis of high-grade large cell neuroendocrine carcinoma of the uterine cervix was made with FIGO stage IIA2. She was treated with chemotherapy and palliative radiotherapy but died 21 months after presenting. Neuroendocrine tumour of the uterine cervix is an extremely aggressive cancer with the late presentation-the need for a more rigorous treatment protocol as well as potential screening methods could improve outcomes for these patients.

PMID: 30642849 [PubMed - in process]
Complete tumor response of a locally advanced lung large-cell neuroendocrine carcinoma after palliative thoracic radiotherapy and immunotherapy with nivolumab.

Fetched: January 17th, 2019, 5:01am GMT

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Complete tumor response of a locally advanced lung large-cell neuroendocrine carcinoma after palliative thoracic radiotherapy and immunotherapy with nivolumab.

Lung Cancer. 2019 Feb;128:53-56

Authors: Mauclet C, Duplaquet F, Pirard L, Rondelet B, Dupont M, Pop-Stanciu C, Vander Borght T, Remmelink M, D'Haene N, Lambin S, Wanet M, Remouchamps V, Ocak S

Abstract
Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

PMID: 30642453 [PubMed - in process]
Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors.

Fetched: January 17th, 2019, 5:01am GMT

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Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors.

BMC Cancer. 2019 Jan 14;19(1):66

Authors: Dromain C, Pavel ME, Ruszniewski P, Langley A, Massien C, Baudin E, Caplin ME, CLARINET Study Group

Abstract
BACKGROUND: Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged progression-free survival (PFS) versus placebo.
METHODS: During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors [RECIST] v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR0); 12-24 weeks before randomization versus baseline; each treatment visit versus baseline (TGRTx-0); between consecutive treatment visits (TGRTx-Tx). To assess TGR as a measure of prognosis, PFS was compared for TGR0 subgroups stratified by optimum TGR0 cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS.
RESULTS: TGR0 revealed tumors growing during pre-treatment (median [interquartile range] TGR0: lanreotide 2.1%/month [0.2; 6.1]; placebo 2.7%/month [0.15; 6.8]), contrary to RECIST status. TGR was significantly reduced by 12 weeks with lanreotide versus placebo (difference in least-square mean TGR0-12 of - 2.9 [- 5.1, - 0.8], p = 0.008), a difference that was maintained at most subsequent visits. TGR0 > 4%/month had greater risk of progression/death than ≤4%/month (hazard ratio 4.1; [95% CI 2.5-6.5]; p < 0.001); multivariate analysis revealed lanreotide treatment, progression at baseline, TGR0, hepatic tumor load, and primary tumor type were independently associated with PFS.
CONCLUSIONS: TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity.
TRIAL REGISTRATION: Retrospective registration, 18 July 2006; EudraCT: 2005-004904-35; ClinicalTrials.gov: NCT00353496 .

PMID: 30642293 [PubMed - in process]
Large Cell Neuroendocrine Carcinoma of the Extrahepatic Bile Duct.

Fetched: January 17th, 2019, 5:01am GMT

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Large Cell Neuroendocrine Carcinoma of the Extrahepatic Bile Duct.

Korean J Gastroenterol. 2018 Dec 25;72(6):318-321

Authors: Park JY, Jeon TJ

Abstract
Primary neuroendocrine tumors originating from the extrahepatic bile duct are rare. Among these tumors, large cell neuroendocrine carcinomas (NECs) are extremely rare. A 59-year-old man was admitted to Sanggye Paik Hospital with jaundice that started 10 days previously. He had a history of laparoscopic cholecystectomy, which he had undergone 12 years previously due to chronic calculous cholecystitis. Laboratory data showed abnormally elevated levels of total bilirubin 15.3 mg/dL (normal 0.2-1.2 mg/dL), AST 200 IU (normal 0-40 IU), ALT 390 IU (normal 0-40 IU), and gamma-glutamyl transferase 1,288 U/L (normal 0-60 U/L). Serum CEA was normal, but CA 19-9 was elevated 5,863 U/mL (normal 0-37 U/mL). Abdominal CT revealed a 4.5 cm sized mass involving the common bile duct and liver hilum and dilatation of both intrahepatic ducts. Percutaneous transhepatic drainage in the left hepatic duct was performed for preoperative biliary drainage. The patient underwent radical common bile duct and Roux-en-Y hepaticojejunostomy for histopathological diagnosis and surgical excision. On histopathological examination, the tumor exhibited large cell NEC (mitotic index >20/10 high-power field, Ki-67 index >20%, CD56 [+], synaptophysin [+], chromogranin [+]). Adjuvant concurrent chemotherapy and radiotherapy were started because the tumor had invaded the proximal resection margin. No recurrence was detected at 10 months by follow-up CT.

PMID: 30642152 [PubMed - in process]
Clinicopathological characteristics and mutation profile of BRAF and NRAS mutation in cutaneous melanomas in the Western Turkish population

Fetched: January 17th, 2019, 5:01am GMT

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Clinicopathological characteristics and mutation profile of BRAF and NRAS mutation in cutaneous melanomas in the Western Turkish population

Turk J Med Sci. 2018 Oct 31;48(5):973-979

Authors: Evrenos MK, Temiz P, Çam FS, Yaman M, Yoleri L, Ermertcan AT

Abstract
Background/aim: Malignant melanoma is the most common cause of death due to skin cancers. The most common mutations in RAFRAS pathway from tumor oncogenes are BRAF and NRAS. In this study, we analyzed the frequency of BRAF and NRAS gene mutations and investigated their association with clinicopathological features of melanomas in the Turkish population. Materials and methods: 65 primary cutaneous melanoma were included in the study. The mutations were evaluated with real-time PCRbased PCR-array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Results: 52.3% of the patients were female and 47.7% were male. The mean age of the patients with a mutation was lower than those without mutation. 16 patients had BRAF mutation. 12 patients had NRAS mutation. NRAS mutation was statistically more common in men (P = 0.036). The number of mitoses increased with the increase of the tumor thickness (P = 0.003). There was more mitosis in the presence of ulceration (P = 0.05). A total of 41.7% of NRAS mutations had adjuvant chemotherapy. Conclusion: We found lower mutation rate when compared to regional studies. NRAS mutation was common in men. This is the first study from our region evaluating the prognostic value of clinical stage and necessity of adjuvant treatment with the presence of BRAF and NRAS mutations.

PMID: 30384563 [PubMed - indexed for MEDLINE]
Enchondroma of Tibia as Potential False-positive Finding on 68Ga-DOTATOC PET/CT Scan.

Fetched: January 17th, 2019, 5:01am GMT

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Enchondroma of Tibia as Potential False-positive Finding on 68Ga-DOTATOC PET/CT Scan.

Clin Nucl Med. 2019 Jan;44(1):e57-e59

Authors: Mahajan S, Bodei L, Huicochea Castellanos S, Grewal RK

Abstract
A 70-year-old man with a history of carcinoid tumor of small bowel was referred for Ga-DOTATOC study to evaluate the extent of disease. PET/CT scan revealed known metastatic disease in the liver, with other sites of involvement including pancreas, peritoneum, and bones. In addition, moderately intense uptake was noted in proximal right tibia and further correlation on CT showed metaphyseal lesion with "rings and arcs" calcification suggestive of enchondroma. This case highlights the possibility of overexpression of somatostatin receptors in enchondromas, which has been little explored in literature.

PMID: 30371598 [PubMed - indexed for MEDLINE]
Genetic profiling of melanoma in routine diagnostics: assay performance and molecular characteristics in a consecutive series of 274 cases.

Fetched: January 17th, 2019, 5:01am GMT

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Genetic profiling of melanoma in routine diagnostics: assay performance and molecular characteristics in a consecutive series of 274 cases.

Pathology. 2018 Dec;50(7):703-710

Authors: Leichsenring J, Stögbauer F, Volckmar AL, Buchhalter I, Oliveira C, Kirchner M, Fröhling S, Hassel J, Enk A, Schirmacher P, Endris V, Penzel R, Stenzinger A

Abstract
A deeper understanding of melanoma biology has opened up new avenues for mechanistically informed therapies. However, data on the prevalence of druggable genetic lesions in melanoma are still conflicting and real-world performance data on high-throughput genetic profiling of melanoma cases using formalin fixed, paraffin embedded (FFPE) tissue with variable tumour cellularity and quality are lacking. We retrospectively analysed targeted next-generation sequencing data of 274 consecutive melanoma samples obtained for routine diagnostics between December 2013 and July 2017. Actionable mutations were detected in 197 cases (71.9%), of which activating BRAF (mostly p.V600E/K) and RAS (mostly p.Q61R/K) mutations occurred in 40.5% (n = 111) and 30.3% (n = 83) of cases, respectively. We identified driver mutations of the Triple-WT subgroup in 10.6% of cases (n = 29; 10 with activating KIT mutations). Median turnaround time was 5 working days with no dropouts. Tumour cellularity ranged from 5% to 95% and successful sequencing was possible at DNA concentrations as low as 0.03 ng/μL (median 10.58 ng/μL; range 0.03-209.05 ng/μL). Fast, quality-controlled high-throughput genetic profiling of FFPE melanoma samples is feasible and provides a landscape of genetic aberrations in melanoma that is currently relevant in clinical practice and approximates TCGA subtypes.

PMID: 30348504 [PubMed - indexed for MEDLINE]
Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension.

Fetched: January 17th, 2019, 5:01am GMT

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Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension.

Int J Mol Sci. 2018 Oct 20;19(10):

Authors: Milling RV, Grimm D, Krüger M, Grosse J, Kopp S, Bauer J, Infanger M, Wehland M

Abstract
Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented.

PMID: 30347815 [PubMed - indexed for MEDLINE]
Cytotoxicity of xyloglucan from Copaifera langsdorffii and its complex with oxovanadium (IV/V) on B16F10 cells.

Fetched: January 17th, 2019, 5:01am GMT

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Cytotoxicity of xyloglucan from Copaifera langsdorffii and its complex with oxovanadium (IV/V) on B16F10 cells.

Int J Biol Macromol. 2019 Jan;121:1019-1028

Authors: Farias CLA, Martinez GR, Cadena SMSC, Mercê ALR, de Oliveira Petkowicz CL, Noleto GR

Abstract
The aim of this study was to investigate the effects of xyloglucan extracted from Copaifera langsdorffii seeds (XGC) and its complex with oxovanadium (XGC:VO) in murine melanoma B16F10 cells. The formation of complexes was followed by potentiometric titration and further demonstrated by 51V RMN. The viability and proliferation of B16F10 cells were reduced up 50% by the xyloglucan and its complex, both at 200 μg/mL, from 24 to 72 h. Cytotoxic effects of XGC and XGC:VO do not involve changes in cell cycle progression. Only XGC:VO (200 μg/mL) promoted the cell death evidenced by annexin V stain. XGC increased the respiration and lactate levels in melanoma cells, while XGC:VO reduced about 50% the respiration and levels of pyruvate, without alter the lactate levels, indicating that both xyloglucan preparations interfere with the metabolism of B16F10 cells. No change in activity of the enzyme hexokinase and expression of pyruvate kinase M2 was observed. XGC:VO (200 μg/mL) negatively modulated the expression of the β subunit of ATP synthase. The results demonstrate that the cytotoxicity of XGC and XGC:VO on murine melanoma B16F10 cells can be related to the impairment of the mitochondrial functions linked to energy provision.

PMID: 30340004 [PubMed - indexed for MEDLINE]
Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Fetched: January 17th, 2019, 5:01am GMT

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Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Nat Commun. 2018 09 24;9(1):3868

Authors: Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, Valente WJ, Koelle SJ, Church CD, Vandeven N, Thomas H, Colunga AG, Iyer JG, Yee C, Kulikauskas R, Koelle DM, Pierce RH, Bielas JH, Greenberg PD, Bhatia S, Gottardo R, Nghiem P, Chapuis AG

Abstract
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.

PMID: 30250229 [PubMed - indexed for MEDLINE]
Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis.

Fetched: January 17th, 2019, 5:01am GMT

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Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis.

PLoS Genet. 2018 09;14(9):e1007589

Authors: Hendricks WPD, Zismann V, Sivaprakasam K, Legendre C, Poorman K, Tembe W, Perdigones N, Kiefer J, Liang W, DeLuca V, Stark M, Ruhe A, Froman R, Duesbery NS, Washington M, Aldrich J, Neff MW, Huentelman MJ, Hayward N, Brown K, Thamm D, Post G, Khanna C, Davis B, Breen M, Sekulic A, Trent JM

Abstract
Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.

PMID: 30188888 [PubMed - indexed for MEDLINE]
Transnasal endoscopic surgery in selected nasal-ethmoidal cancer with suspected brain invasion: Indications, technique, and outcomes.

Fetched: January 14th, 2019, 5:01am GMT

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Transnasal endoscopic surgery in selected nasal-ethmoidal cancer with suspected brain invasion: Indications, technique, and outcomes.

Head Neck. 2019 Jan 12;:

Authors: Mattavelli D, Ferrari M, Bolzoni Villaret A, Schreiber A, Rampinelli V, Turri-Zanoni M, Lancini D, Taglietti V, Accorona R, Doglietto F, Battaglia P, Castelnuovo P, Nicolai P

Abstract
BACKGROUND: In nasal-ethmoidal malignancies, brain involvement is associated with dismal prognosis.
METHOD: Patients undergoing endoscopic resection with transnasal craniectomy and subpial dissection (ERTC-SD) for brain-invading nasal-ethmoidal cancer between 2008 and 2016 were included. Complications were analyzed in all patients, whereas oncological outcomes only in patients with pathological brain invasion. The prognostic impact of previous treatments, brain edema, and histology was assessed. Hospitalization ratio was calculated.
RESULTS: Nineteen patients received ERTC-SD and 11 had pathological-proven brain invasion. Histologies were 6 olfactory neuroblastomas (ONB), 3 neuroendocrine carcinomas, and 2 intestinal-type adenocarcinomas. Mean follow-up was 21.9 months. Three-year overall, local recurrence-free, and distance recurrence-free survivals were 65.5%, 81.8%, and 68.2%, respectively. Overall and distant recurrence-free survivals were significantly better in patients with ONB (P = 0.032 and P = 0.013, respectively). Hospitalization ratio was 4.1%. Complication rate was 10.5%.
CONCLUSION: In selected nasal-ethmoidal tumors with brain invasion, ERTC-SD can provide good local control, satisfactory survival, and limited morbidity.

PMID: 30636181 [PubMed - as supplied by publisher]
The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice.

Fetched: January 14th, 2019, 5:01am GMT

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The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice.

Endocrine. 2019 Jan 11;:

Authors: Alexandraki KI, Pizanias M, Uri I, Thomas D, Page T, Kolomodi D, Low CS, Adesanya O, Tsoli M, Gross DJ, Randeva H, Srirajaskanthan R, Grozinsky-Glasberg S, Kaltsas G, Weickert MO

Abstract
PURPOSE: To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs).
METHODS: Seventy-four patients were recruited from four NEN centers in this observational multicenter study.
RESULTS: Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4-395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589-14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14-463) months.
CONCLUSIONS: Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

PMID: 30635793 [PubMed - as supplied by publisher]
Current Treatment Options in Gastroenteropancreatic Neuroendocrine Carcinoma.

Fetched: January 14th, 2019, 5:01am GMT

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Current Treatment Options in Gastroenteropancreatic Neuroendocrine Carcinoma.

Oncologist. 2019 Jan 11;:

Authors: Thomas KEH, Voros BA, Boudreaux JP, Thiagarajan R, Woltering EA, Ramirez RA

Abstract
Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first-line treatment for GEPNECs is platinum-based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first-line and second-line treatment options beyond platinum-based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low- and intermediate-grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy. IMPLICATIONS FOR PRACTICE: There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first- and second-line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.

PMID: 30635447 [PubMed - as supplied by publisher]
Outcomes After Transarterial Embolization of Neuroendocrine Tumor Liver Metastases Using Spherical Particles of Different Sizes.

Fetched: January 12th, 2019, 5:00am GMT

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Outcomes After Transarterial Embolization of Neuroendocrine Tumor Liver Metastases Using Spherical Particles of Different Sizes.

Cardiovasc Intervent Radiol. 2019 Jan 09;:

Authors: Zener R, Yoon H, Ziv E, Covey A, Brown KT, Sofocleous CT, Thornton RH, Boas FE

Abstract
PURPOSE: To evaluate initial response and overall survival of neuroendocrine tumor (NET) liver metastases initially treated with transarterial embolization (TAE) using spherical particles of different sizes.
METHODS: A single-institution retrospective review was performed of 160 patients with NET liver metastases initially treated with TAE using < 100 µm (n = 77) or only ≥ 100 µm (n = 83) spherical particles. For each patient, we evaluated: initial response by mRECIST, time to progression, overall survival, complications, primary site, tumor grade and degree of differentiation, volume of liver disease, extrahepatic disease, NET-related symptoms, comorbidities, Child-Pugh score, performance status, lobar versus selective embolization, and arteriovenous shunting.
RESULTS: Initial response was higher for TAE using particles < 100 versus TAE using only particles ≥ 100 μm (64 vs 42%, p = 0.007). Multivariate logistic regression showed that use of particles < 100 μm and liver < 50% replaced with tumor were independent predictors of a better initial response rate. There was no difference in major or minor complications between the two particle size groups. Median overall survival after TAE was 55 months for well- to moderately differentiated NET and 13 months for poorly differentiated or undifferentiated NET. There was no significant difference in survival between TAE patients treated with < 100 versus only ≥ 100-μm particles.
CONCLUSION: NET patients treated with TAE using particles < 100 μm had better initial response, but the same overall survival, compared to TAE using only particles ≥ 100 μm.

PMID: 30627774 [PubMed - as supplied by publisher]
Grading of Neuroendocrine Carcinomas: Correlation of 68Ga-PET/CT Scan with Tissue Biomarkers.

Fetched: January 12th, 2019, 5:00am GMT

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Grading of Neuroendocrine Carcinomas: Correlation of 68Ga-PET/CT Scan with Tissue Biomarkers.

Dis Markers. 2018;2018:6878409

Authors: Liverani C, Bongiovanni A, Mercatali L, Foca F, Pieri F, De Vita A, Spadazzi C, Miserocchi G, Recine F, Riva N, Nicolini S, Severi S, Martinelli G, Ibrahim T

Abstract
There is a growing need for more accurate biomarkers to facilitate the diagnosis and prognosis of patients with grade (G) 3 neuroendocrine carcinomas (NECs). In particular, the discrimination between well-differentiated neuroendocrine carcinomas (WD-NECs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) is still an unmet need. We previously showed that 68Gallium-(68Ga-) PET/CT positivity is a prognostic factor in patients with gastroenteropancreatic (GEP) G3 NECs, correlating with a better outcome in terms of overall survival. Here, we hypothesize that 68Ga-PET/CT could help to discriminate between WD-NECs and PD-NECs, adding complementary information to that obtained from morphologic and biologic factors. A retrospective, single-institution study was performed on 11 patients with histologically confirmed, measurable G3 large- or small-cell GEP-NECs according to the 2017 WHO classification. The staging procedures included a 68Ga-PET/CT scan. Results of 68Ga-PET/CT were correlated in univariate analysis with loss of tissue immunohistochemical expression of DAXX/ATRX or RB1 frequently associated with WD-NECs or PD-NECs, respectively. None of the patients with positive 68Ga-PET/CT showed loss of RB1 expression, whereas among those (n = 6) with negative 68Ga-PET/CT, 4 showed loss of expression. A trend towards a correlation between loss of RB1 expression and negative 68Ga-PET/CT was observed. Our preliminary data support the hypothesis that PD-NECs carrying RB1 mutation and loss of its expression may be associated with negative 68Ga-PET/CT. If confirmed in a larger clinical trial, 68Ga-PET/CT would help in the stratification of G3 NECs.

PMID: 30627226 [PubMed - in process]
What Is New in the 2017 World Health Organization Classification and 8th American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Neoplasms?

Fetched: January 12th, 2019, 5:00am GMT

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What Is New in the 2017 World Health Organization Classification and 8th American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Neoplasms?

Korean J Radiol. 2019 Jan;20(1):5-17

Authors: Choe J, Kim KW, Kim HJ, Kim DW, Kim KP, Hong SM, Ryu JS, Tirumani SH, Krajewski K, Ramaiya N

Abstract
The diagnosis and management of pancreatic neuroendocrine neoplasms (NENs) have evolved significantly in recent years. There are several diagnostic and therapeutic challenges and controversies regarding the management of these lesions. In this review, we focus on the recent significant changes and controversial issues regarding the diagnosis and management of NENs and discuss the role of imaging in the multidisciplinary team approach.

PMID: 30627018 [PubMed - in process]
A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.

Fetched: January 12th, 2019, 5:00am GMT

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A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.

Nat Commun. 2019 Jan 09;10(1):96

Authors: Mahoney CE, Pirman D, Chubukov V, Sleger T, Hayes S, Fan ZP, Allen EL, Chen Y, Huang L, Liu M, Zhang Y, McDonald G, Narayanaswamy R, Choe S, Chen Y, Gross S, Cianchetta G, Padyana AK, Murray S, Liu W, Marks KM, Murtie J, Dorsch M, Jin S, Nagaraja N, Biller SA, Roddy T, Popovici-Muller J, Smolen GA

Abstract
Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers.

PMID: 30626880 [PubMed - in process]
[Case of paraganglioma mimicking lymph node metastasis from a pancreatic neuroendocrine neoplasm].

Fetched: January 12th, 2019, 5:00am GMT

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[Case of paraganglioma mimicking lymph node metastasis from a pancreatic neuroendocrine neoplasm].

Nihon Shokakibyo Gakkai Zasshi. 2019;116(1):80-87

Authors: Osawa L, Shindo H, Fukasawa M, Takano S, Takahashi E, Hirose S, Sato T, Hosomura N, Kawaida H, Enomoto N

Abstract
A 79-year-old woman with a history of hypertension presented with lumbago. Magnetic resonance imaging revealed a retroperitoneal mass. Computed tomography revealed another contrast-enhanced mass in the pancreatic tail. We performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the pancreatic mass and diagnosed it as a pancreatic neuroendocrine neoplasm (PanNEN). The retroperitoneal mass was thought to be lymph node metastases of the PanNEN. During surgical resection, severe hypertension occurred when the retroperitoneal mass was manipulated. The pathological diagnosis was a G1 neuroendocrine tumor of the pancreatic tail and a paraganglioma. Neuroendocrine neoplasms and paraganglioma demonstrated similar findings on imaging studies. However, FNA of a paraganglioma puts the patient at risk of severe hypertension. We suggest differentiating between PanNEN and paraganglioma before EUS-FNA.

PMID: 30626858 [PubMed - in process]
Rectal Submucosal Tumor Mimicking a Neuroendocrine Tumor.

Fetched: January 12th, 2019, 5:00am GMT

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Rectal Submucosal Tumor Mimicking a Neuroendocrine Tumor.

Intern Med. 2019 Jan 10;:

Authors: Utsumi T, Yamada A, Sakurai T, Miyamoto S

PMID: 30626842 [PubMed - as supplied by publisher]
The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

Fetched: January 12th, 2019, 5:00am GMT

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The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

Neuroendocrinology. 2018;107(3):284-291

Authors: Kruljac I, Vičić I, Blaslov K, Kolak Z, Benković M, Kust D, Ladika Davidović B, Tometić G, Penavić I, Dabelić N, Vazdar L, Pavić T, Vrkljan M

Abstract
BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA.
METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration.
RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%.
CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

PMID: 30114698 [PubMed - indexed for MEDLINE]
The Risk of Second Primary Colorectal Adenocarcinomas Is Not Increased among Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Nationwide Population-Based Study.

Fetched: January 12th, 2019, 5:00am GMT

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The Risk of Second Primary Colorectal Adenocarcinomas Is Not Increased among Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Nationwide Population-Based Study.

Neuroendocrinology. 2018;107(3):280-283

Authors: Stemann Lau T, Dam G, Jepsen P, Grønbæk H, Krogh K, Gregersen T

Abstract
BACKGROUND: Second primary colorectal adenocarcinomas (SPCA) may occur with a higher frequency in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In a nationwide population-based study, we investigated the risk of SPCA in GEP-NEN patients and compared it to the general population.
METHODS: Using the nationwide Danish registries, we identified 2,831 GEP-NEN patients (median age 63 years [IQR 50-73 years], 53% women) diagnosed in 1995-2010. We used Cox regression to compare the incidence of SPCA in GEP-NEN patients relative to a gender- and age-matched general population sample of 56,044 persons.
RESULTS: We observed 20 SPCAs among the 2,831 GEP-NEN patients with a total time at risk of 14,003 years (incidence = 143 per 100,000 person-years) and 770 colorectal adenocarcinomas in the general population of 56,044 persons with a total time at risk of 466,801 years (incidence = 165 per 100,000 person-years). The hazard ratio (HR) of SPCA from GEP-NEN diagnosis to the end of follow-up was 1.22 (95% CI: 0.78-1.92) in GEP-NEN patients compared to the general population. This nonsignificant association was the result of a strong positive association in the first 6 months after diagnosis of GEP-NEN (HR = 9.43 [95% CI: 4.98-17.86]) followed by a negative association in the remainder of the follow-up period (HR = 0.50 [95% CI: 0.20-1.21]).
CONCLUSION: In this population-based study, there was no increased risk of SPCA among GEP-NEN patients. The clinical workup in newly diagnosed GEP-NEN patients likely explains the positive short-term association followed by a negative association.

PMID: 30092588 [PubMed - indexed for MEDLINE]
Exercise cardiac magnetic resonance imaging with pulmonary artery catheter monitoring in carcinoid heart disease: a shift towards early intervention?

Fetched: January 12th, 2019, 5:00am GMT

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Exercise cardiac magnetic resonance imaging with pulmonary artery catheter monitoring in carcinoid heart disease: a shift towards early intervention?

ESC Heart Fail. 2018 10;5(5):953-955

Authors: Timmermans P, Rega F, Bogaert J, Herregods MC

Abstract
Neuroendocrine tumours are a rare malignancy, which can be complicated by a carcinoid syndrome and, in more rare cases, also valve destruction. The correct timing for surgical repair remains unknown. We report the first-in-men exercise cardiac magnetic resonance imaging with pulmonary artery catheter measurements in order to better understand the haemodynamic impact of isolated tricuspid valve insufficiency in a low symptomatic patient. Not pressure but volume overload is the key factor in the development of symptoms, as long as the right ventricular function is intact. Based on our findings, we referred the patient for tricuspid valve replacement. This case, together with the review of all carcinoid heart disease cases in our hospital (a large tertiary cardiology and oncology centre) since 2000, indicates a potential benefit for early intervention in carcinoid heart disease.

PMID: 30080311 [PubMed - indexed for MEDLINE]
Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model.

Fetched: January 12th, 2019, 5:00am GMT

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Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model.

Neuroendocrinology. 2018;107(3):257-266

Authors: Manoharan J, Fendrich V, Di Fazio P, Bollmann C, Roth S, Joos B, Mintziras I, Albers MB, Ramaswamy A, Bertolino P, Zhang CX, Slater EP, Bartsch DK, Lopez-Lopez CL

Abstract
Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm2, p < 0.001) and 79% (174,758 vs. 838,876 µm2, p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin-treated Men1(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

PMID: 30025403 [PubMed - indexed for MEDLINE]
18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Fetched: January 12th, 2019, 5:00am GMT

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18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Neuroendocrinology. 2018;107(3):228-236

Authors: Moog S, Houy S, Chevalier E, Ory S, Weryha G, Rame M, Klein M, Brunaud L, Gasman S, Cuny T

Abstract
BACKGROUND: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied.
METHODS: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic burden [MB] calculated as follows: MB = SUVmean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry.
RESULTS: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01).
CONCLUSION: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that 18F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.

PMID: 29949805 [PubMed - indexed for MEDLINE]
Diagnosis of retrocochlear lesions with emphasis on expansion of the cerebellopontine angle.

Fetched: January 12th, 2019, 5:00am GMT

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Diagnosis of retrocochlear lesions with emphasis on expansion of the cerebellopontine angle.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018 Sep;162(3):178-183

Authors: Gal B, Rottenberg J, Pazourkova M, Vanicek J, Vogazianos E

Abstract
The correct diagnosis of CPA tumours is a relatively common issue in both neurological and ENT practice, the omission of which can have serious consequences for the patient. Properly set clinical guidelines and diagnostic protocols are key aspects of good clinical practice. In the case of CPA tumours, two options are available: the first is diagnosis with the help of an ABR as the primary tool for determining the group of patients with a possible tumour; the second is an MRI scan of the posterior cranial fossa. With an appropriately set diagnostic protocol in place, and despite the 40% chance of failure of the ABR to detect tumours less than or equal to 1 cm, similar treatment results can be achieved with much higher cost efficacy in case of primary ABR testing.

PMID: 29765166 [PubMed - indexed for MEDLINE]
Subclassification of Bethesda Atypical and Follicular Neoplasm Categories According to Nuclear and Architectural Atypia Improves Discrimination of Thyroid Malignancy Risk.

Fetched: January 12th, 2019, 5:00am GMT

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Subclassification of Bethesda Atypical and Follicular Neoplasm Categories According to Nuclear and Architectural Atypia Improves Discrimination of Thyroid Malignancy Risk.

Thyroid. 2018 04;28(4):511-521

Authors: Lim JXY, Nga ME, Chan DKH, Tan WB, Parameswaran R, Ngiam KY

Abstract
BACKGROUND: Although The Bethesda System for Reporting Thyroid Cytopathology has provided clinicians with a standardized classification scheme for the diagnosis of thyroid fine-needle aspiration cytology (FNAC) specimens, the indeterminate categories of Bethesda III (B3)-atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)-and Bethesda IV (B4)-follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)-continue to pose challenges with regards to ideal diagnostic and therapeutic management. Having previously demonstrated the presence of nuclear atypia as a high-risk subgroup in B3, the objective of this study was to evaluate the malignancy rates in the B4 subgroup with nuclear atypia.
METHODS: A retrospective review of all thyroid FNACs diagnosed as B4 (FN/SFN) between 2008 and 2015 was conducted at a tertiary referral center in Singapore. Data on patient demographics, sonographic features, and final histological diagnosis were collected. This was compared to data from a previous analysis on all nodules diagnosed as B3 (AUS/FLUS) over a similar period.
RESULTS: A total of 137/309 (44.3%) and 88/111 (79.3%) FNACs diagnosed as B3 and B4, respectively, underwent surgical excision yielding final histopathological diagnoses. The malignancy rate of B4 was 31/88 (35.2%) compared to B3, which was 37/137 (27.0%). Subclassification based on the presence of architectural versus nuclear atypia showed significantly higher malignancy rates in B4 nodules with nuclear atypia (21.8% vs. 57.6%; p < 0.01). These findings corroborate previous results within the B3 category (malignancy rate of 14.7% vs. 36.8%; p < 0.01). The only sonographic features predictive of malignancy were the presence of macrocalcifications in B4 compared to irregularity of margins in B3.
CONCLUSION: The presence of nuclear atypia identifies subgroups with significant differential malignancy risks within both the B3 and B4 categories. This supports the notion that subclassification is a useful risk stratification tool that can guide diagnostic and therapeutic management of indeterminate thyroid nodules with heterogenous risk profiles.

PMID: 29596039 [PubMed - indexed for MEDLINE]
[Metastatic melanoma in placenta: A new case with PDL1 immunostaining].

Fetched: January 12th, 2019, 5:00am GMT

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[Metastatic melanoma in placenta: A new case with PDL1 immunostaining].

Ann Pathol. 2017 Aug;37(4):338

Authors: Poreau B, Sartelet H

PMID: 28754220 [PubMed - indexed for MEDLINE]
MR imaging features of benign retroperitoneal extra-adrenal paragangliomas.

Fetched: January 12th, 2019, 5:00am GMT

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MR imaging features of benign retroperitoneal extra-adrenal paragangliomas.

Sci Rep. 2017 07 03;7(1):4517

Authors: Shen Y, Zhong Y, Wang H, Ma L, Wang Y, Pan J, Zhang K, Sun Z, Ye H

Abstract
The goal of this study was to retrospectively review the magnetic resonance imaging (MRI) features of retroperitoneal extra-adrenal paragangliomas and to evaluate the diagnostic capabilities of MRI. Twenty-four patients with confirmed benign retroperitoneal extra-adrenal paragangliomas who underwent preoperative MRI and surgical resection were enrolled. The patients' clinical characteristics and MRI features were reviewed by two radiologists. There were no significant differences in the qualitative and quantitative MRI features were determined by the reviewers. High signal intensity in T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) was observed in all tumors. In contrast T1-weighted imaging (T1WI) in the arterial phase, 83.33% of the tumors were clearly enhanced. In 87.5% of cases, a persistent enhancement pattern was observed in the venous and delayed phases, and 12.5% of tumors showed a "washout" pattern. The tumor capsule, intratumoral septum and degenerations were visualized in the tumors and may be helpful in the qualitative diagnosis of extra-adrenal paragangliomas in MRI. MRI was useful in locating the position, determining the tumor ranges and visualizing the relationship between the tumors and adjacent structures. The presence of typical clinical symptoms and positivity of biochemical tests are also important factors in making an accurate preoperative diagnosis.

PMID: 28674383 [PubMed - indexed for MEDLINE]
Using Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy to distinguish between melanoma cells with a different metastatic potential.

Fetched: January 12th, 2019, 5:00am GMT

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Using Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy to distinguish between melanoma cells with a different metastatic potential.

Sci Rep. 2017 06 29;7(1):4381

Authors: Minnes R, Nissinmann M, Maizels Y, Gerlitz G, Katzir A, Raichlin Y

Abstract
The vast majority of cancer related deaths are caused by metastatic tumors. Therefore, identifying the metastatic potential of cancer cells is of great importance both for prognosis and for determining the correct treatment. Infrared (IR) spectroscopy of biological cells is an evolving research area, whose main aim is to find the spectral differences between diseased and healthy cells. In the present study, we demonstrate that Attenuated Total Reflection Fourier Transform IR (ATR-FTIR) spectroscopy may be used to determine the metastatic potential of cancer cells. Using the ATR-FTIR spectroscopy, we can identify spectral alterations that are a result of hydration or molecular changes. We examined two murine melanoma cells with a common genetic background but a different metastatic level, and similarly, two human melanoma cells. Our findings revealed that higher metastatic potential correlates with membrane hydration level. Measuring the spectral properties of the cells allows us to determine the membrane hydration levels. Thus, ATR-FTIR spectroscopy has the potential to help in cancer metastasis prognosis.

PMID: 28663552 [PubMed - indexed for MEDLINE]
Prognostic value of CD146 in solid tumor: A Systematic Review and Meta-analysis.

Fetched: January 12th, 2019, 5:00am GMT

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Prognostic value of CD146 in solid tumor: A Systematic Review and Meta-analysis.

Sci Rep. 2017 06 26;7(1):4223

Authors: Zeng P, Li H, Lu PH, Zhou LN, Tang M, Liu CY, Chen MB

Abstract
CD146, also known as melanoma cell adhesion molecule, was initially identified as a marker of melanoma progression and metastasis. Recently many clinical studies investigated overexpression of CD146 predict poor prognosis of solid tumor, however, the results was inconclusive, partly due to small numbers of patients included. This present meta-analysis was therefore performed utilizing the results of all clinical studies concerned to determine the prognostic value of CD146 expression in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. In this meta-analysis, 12 studies involving 2,694 participants were included, and we drew the conclusion that strong significant associations between CD146 expression and all endpoints: overall survival (OS) [hazard ratio (HR) = 2.496, 95% confidence interval (95% CI) 2.115-2.946], time to progression (TTP) (HR = 2.445, 95% CI 1.975-3.027). Furthermore, the subgroup analysis revealed that the associations between CD146 overexpression and the outcome endpoints (OS or TTP) were significant in Mongoloid patients and Caucasian patients, as well in patients with lung cancer and digestive system cancer. In conclusion, these results showed that high CD146 was associated with poor survival in human solid tumors. CD146 may be a valuable prognosis predictive biomarker; nevertheless, whether CD146 could be a potential therapeutic target in human solid tumors needs to be further studied.

PMID: 28652617 [PubMed - indexed for MEDLINE]
Carcinoid heart disease involving the left heart: a case report and biomarker analysis.

Fetched: January 10th, 2019, 5:00am GMT

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Carcinoid heart disease involving the left heart: a case report and biomarker analysis.

ESC Heart Fail. 2019 Jan 08;:

Authors: Lichtenauer M, Pichler T, Eder S, Mirna M, Magnes T, Wernly B, Paar V, Jung C, Prinz E, Seitelberger R, Hoppe UC

Abstract
Herein, we report the case of a 67-year-old woman who was admitted to our hospital because of dyspnoea and oedema of the lower extremities. Transthoracic echocardiography revealed severe tricuspid and mitral regurgitation, and the leaflets of the tricuspid valve were found to be rigid and almost immobile. The plasma concentrations of serotonin and chromogranin A were elevated, and hence, suspicion for carcinoid heart disease was raised. In addition to the diagnostic workup and medical and surgical treatment, we analysed levels of novel cardiovascular biomarkers throughout the entire follow-up by means of enzyme-linked immunosorbent assay. A dopa positron emission tomography (DOPA-PET) was conducted and showed a neoplasm in the terminal ileum. Tricuspid valve replacement, mitral valve repair, and a closure of the patent foramen ovale (PFO) were conducted. Two months later, hemicolectomy and liver segment resection were performed. The tumour was resected, and the diagnosis of a neuroendocrine tumour (NET) was confirmed. Throughout the follow-up, we observed a decrease in the plasma levels of novel biomarkers [e.g. interleukin-8 (IL-8), soluble suppression of tumorigenicity-2 (sST2), and heart-type fatty acid-binding protein (H-FABP)] over the follow-up period. In our case, carcinoid heart disease resulted in a severe tricuspid regurgitation as commonly seen in these patients. Moreover, a pre-existent mitral regurgitation was likely aggravated by fibrotic remodelling, because a PFO has led to a right-to-left shunt and might have caused left heart involvement. As IL-8 was associated with adverse outcomes in patients with NETs, and sST2 and H-FABP were associated with adverse outcomes in patients with heart failure previously, these biomarkers could aid in the risk stratification of patients with NET.

PMID: 30620449 [PubMed - as supplied by publisher]
Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.

Fetched: January 10th, 2019, 5:00am GMT

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Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.

Cancer. 2019 Jan 08;:

Authors: Tirosh A, Mukherjee S, Lack J, Gara SK, Wang S, Quezado MM, Keutgen XM, Wu X, Cam M, Kumar S, Patel D, Nilubol N, Tyagi MV, Kebebew E

Abstract
BACKGROUND: Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome-wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs.
METHODS: Thirty-three tissue samples were analyzed: they included samples from sporadic (n = 9), von Hippel-Lindau (VHL)-related (n = 10), and multiple endocrine neoplasia type 1 (MEN1)-related NFPanNETs (n = 10) as well as normal islet cells (n = 4) for comparison. Genome-wide CpG methylation profiling was performed with the Infinium MethylationEPIC BeadChip assay and was analyzed with R-based tools.
RESULTS: In unsupervised hierarchical clustering, sporadic and MEN1-related NFPanNETs clustered together, and the VHL group was in a separate cluster. MEN1-related NFPanNETs had a higher rate of hypermethylated CpG sites in comparison with sporadic and VHL-related tumor groups. Differentially methylated region analysis confirmed the higher rate of hypermethylation in MEN1-related tumors. Moreover, in an integrated analysis of gene expression data for the same tumor samples, downregulated gene expression was found in most genes that were hypermethylated. In a CpG island methylator phenotype analysis, 3 genes were identified and confirmed to have downregulated gene expression: secreted frizzle-related protein 5 (SFRP5) in sporadic NFPanNETs and cell division cycle-associated 7-like (CDCA7L) and RNA binding motif 47 (RBM47) in MEN1-related NFPanNETs.
CONCLUSIONS: MEN1 NFPanNETs have a higher rate of geno me-wide hypermethylation than other NFPanNET subtypes. The similarity between the pathways enriched in a methylation analysis of known genes involved in NFPanNET tumorigenesis suggests a key role for aberrant methylation in the pathogenesis of NFPanNETs.

PMID: 30620390 [PubMed - as supplied by publisher]
Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter?

Fetched: January 10th, 2019, 5:00am GMT

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Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter?

Cancer. 2019 Jan 08;:

Authors: Berg S, D'Andrea D, Vetterlein MW, Cole A, Fletcher SA, Krimphove MJ, Marchese M, Lipsitz SR, Sonpavde G, Noldus J, Shariat SF, Kibel AS, Trinh QD, Mossanen M

Abstract
BACKGROUND: The use of adjuvant chemotherapy (AC) in pure urothelial carcinoma of the bladder is established. Regarding variant histology, there is a gap in knowledge concerning the optimal treatment after radical cystectomy (RC). The objective of this study was to assess the effect of AC on overall survival (OS) in patients who had pure urothelial carcinoma, urothelial carcinoma with concomitant variant histology, or another pure variant histology.
METHODS: Within the National Cancer Data Base, 15,397 patients who underwent RC for nonmetastatic, localized carcinoma of the bladder and had positive lymph nodes (T2N+) or locally advanced stage (≥T3N0/N+) were identified, excluding those who had previously received neoadjuvant chemotherapy. Multivariable Cox regression models were used to examine the specific effect of AC on OS stratified by each distinct histologic subtype, including pure urothelial carcinoma, micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. To account for immortal time bias, Cox regression analyses and Kaplan-Meier analyses were conducted with a landmark at 3 months.
RESULTS: In multivariable landmark analyses, AC compared with initial observation was associated with an OS benefit for patients who had pure urothelial carcinoma (hazard ratio, 0.87; 95% confidence interval, 0.82-0.91), whereas no differences were observed with regard to those who had variant histology.
CONCLUSIONS: Multivariable Cox regression landmark analysis revealed a survival benefit from AC for patients with a pure urothelial carcinoma. However, a survival benefit of AC for patients who had urothelial carcinoma with concomitant variant histology or other pure variant histology was not demonstrated.

PMID: 30620387 [PubMed - as supplied by publisher]
The clinicopathological features and treatment modalities associated with survival of neuroendocrine cervical carcinoma in a Chinese population.

Fetched: January 10th, 2019, 5:00am GMT

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The clinicopathological features and treatment modalities associated with survival of neuroendocrine cervical carcinoma in a Chinese population.

BMC Cancer. 2019 Jan 07;19(1):22

Authors: Zhang X, Lv Z, Lou H

Abstract
BACKGROUND: Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive form of cervical cancer representing less than 3% of all cervical cancer cases. The objective of this study is to evaluate the effects of the clinicopathologic features and treatment modalities on the survival of patients with NECC.
METHODS: In all, 89 stage I-IV patients with NECC that were diagnosed and treated between 2006 and 2014 at the Zhejiang Cancer Hospital were retrospectively recruited in this study. The Kaplan-Meier method, Cox regression analysis models and the log-rank test were used for the statistical analyses.
RESULTS: NECC patients with advanced FIGO stage, tumor size > 4 cm, lymph node metastasis (LNM) and lymph-vascular space invasion (LVSI) were more likely to have significantly worse survival. Neither neo-adjuvant chemotherapy (NACT) nor radiotherapy (RT) was associated with improved overall survival. In the stratified analysis of stage I-IIA patients, those with advanced FIGO stage (P = 0.018), LNM (P = 0.008) and LVSI (P = 0.024) were associated with significantly worse survival. Patients without LNM who did not receive RT had significantly better survival rates than those who received RT (HR = 3.363, 95%CI = 1.245-10.619; P = 0.018). Moreover, for stage I-IIA patients with tumor size > 4 cm, NACT was not associated with a significantly better survival rate compared with no NACT (P = 0.600). None of the clinicopathologic features or treatment modalities was an independent prognostic factor in the multivariate analysis.
CONCLUSIONS: In conclusion, advanced FIGO stage, tumor size > 4 cm, LNM and LVSI were associated with poor survival. For stage I-IIA patients, RT should be carefully used in patients who are negative for LNM, and NACT may not be the optimal treatment for patients with tumor size > 4 cm.

PMID: 30616631 [PubMed - in process]
Fibre supplementation for the prevention of type 2 diabetes and improvement of glucose metabolism: the randomised controlled Optimal Fibre Trial (OptiFiT).

Fetched: January 10th, 2019, 5:00am GMT

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Fibre supplementation for the prevention of type 2 diabetes and improvement of glucose metabolism: the randomised controlled Optimal Fibre Trial (OptiFiT).

Diabetologia. 2018 06;61(6):1295-1305

Authors: Honsek C, Kabisch S, Kemper M, Gerbracht C, Arafat AM, Birkenfeld AL, Dambeck U, Osterhoff MA, Weickert MO, Pfeiffer AFH

Abstract
AIMS/HYPOTHESIS: Insoluble cereal fibres have been shown in large prospective cohort studies to be highly effective in preventing type 2 diabetes, but there is a lack of interventional data. Our 2 year randomised double-blind prospective intervention study compared the effect of an insoluble oat fibre extract with that of placebo on glucose metabolism and incidence of diabetes.
METHODS: A total of 180 participants with impaired glucose tolerance underwent a modified version of the 1 year lifestyle training programme PREvention of DIAbetes Self-management (PREDIAS) and were randomised to receive a fibre supplement (n = 89; 7.5 g of insoluble fibre per serving) or placebo (n = 91; 0.8 g of insoluble fibre per serving) twice daily for 2 years. Eligible participants were men and women, were at least 18 years old and did not report corticosteroid or other intensive anti-inflammatory treatment, fibre intolerance or any of the following disorders: overt diabetes, chronic or malignant disease, or severe cardiopulmonary, endocrine, psychiatric, gastrointestinal, autoimmune or eating disorder. Participants were recruited at two clinical wards in Berlin and Nuthetal. The allocation was blinded to participants and study caregivers (physicians, dietitians, study nurses). Randomisation was conducted by non-clinical staff, providing neutrally numbered supplement tins. Both supplements were similar in their visual, olfactory and gustatory appearance. Intention-to-treat analysis was applied to all individuals.
RESULTS: After 1 year, 2 h OGTT levels decreased significantly in both groups but without a significant difference between the groups (fibre -0.78 ± 1.88 mmol/l [p ≤ 0.001] vs placebo -0.46 ± 1.80 mmol/l [p = 0.020]; total difference 0.32 ± 0.29 mmol/l; not significant). The 2 year incidence of diabetes was 9/89 (fibre group) compared with 16/91 (placebo group; difference not significant). As secondary outcomes, the change in HbA1c level was significantly different between the two groups (-0.2 ± 4.6 mmol/mol [-0.0 ± 0.0%; not significant] vs +1.2 ± 5.2 mmol/mol [+0.1 ± 0.0%; not significant]; total difference 1.4 ± 0.7 mmol/mol [0.1 + 0.0%]); p = 0.018); insulin sensitivity and hepatic insulin clearance increased in both groups. After 2 years, improved insulin sensitivity was still present in both groups, although the effect size had diminished. Separate analysis of the sexes revealed a significantly greater reduction in 2 h glucose levels for women in the fibre group (-0.88 ± 1.59 mmol/l [p ≤ 0.001] vs -0.22 ± 1.52 mmol/l [p = 0.311]; total difference 0.67 ± 0.31 mmol/l; p = 0.015). Levels of fasting glucose, adipokines and inflammatory markers remained unchanged in the two groups. Significantly increased fibre intake was restricted to the fibre group, despite dietary counselling for both groups. No severe side effects occurred.
CONCLUSIONS/INTERPRETATION: We cannot currently provide strong evidence for a beneficial effect of insoluble cereal fibre on glycaemic metabolism, although further studies may support minor effects of fibre supplementation in reducing glucose levels, insulin resistance and the incidence of type 2 diabetes.
TRIAL REGISTRATION: clinicaltrials.gov NCT01681173 Funding: German Diabetes Foundation (grant no. 232/11/08).

PMID: 29492637 [PubMed - indexed for MEDLINE]
The EMT-related transcription factor snail up-regulates FAPα in malignant melanoma cells.

Fetched: January 10th, 2019, 5:00am GMT

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The EMT-related transcription factor snail up-regulates FAPα in malignant melanoma cells.

Exp Cell Res. 2018 03 15;364(2):160-167

Authors: Yi Y, Wang Z, Sun Y, Chen J, Zhang B, Wu M, Li T, Hu L, Zeng J

Abstract
FAPα is a cell surface serine protease, mainly expressed in tumor stromal fibroblasts in more than 90% of human epithelial carcinomas. Due to its almost no expression in normal tissues and its tumor-promoting effects, FAPα has been studied as a novel potential target for antitumor therapy. However, the regulation mechanism on FAPα expression is poorly understood. In this study, we found that overexpression of snail significantly increased the mRNA and protein expression levels of FAPα in malignant melanoma B16 and SK-MEL-28 cells. Overexpression of snail increased FAPα promoter activity remarkably. Snail could directly bind to FAPα promoter to regulate FAPα expression. Moreover, snail expression was positively correlated to FAPα expression in human cutaneous malignant melanoma. Furthermore, knockdown of FAPα markedly reduced snail-induced cell migration. Overall, our findings provide a novel regulation mechanism on FAPα expression and highlight the role of snail/FAPα axis as a novel target for melanoma treatment.

PMID: 29410133 [PubMed - indexed for MEDLINE]
Genome-wide RNA-Seq identifies Fas/FasL-mediated tumoricidal activity of embryonic stem cells.

Fetched: January 10th, 2019, 5:00am GMT

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Genome-wide RNA-Seq identifies Fas/FasL-mediated tumoricidal activity of embryonic stem cells.

Int J Cancer. 2018 05 01;142(9):1829-1841

Authors: Li Y, Fan Y, Xu J, Zhang P, Jiang T, Dai M, Li L

Abstract
The discovery of tumor tropism of stem cells revealed the intimate relationship between stem cells and tumor cells, but the functional role of stem cells in tumorigenesis is poorly understood. To investigate embryonic stem cell (ESC) and tumor cell interactions, we co-cultured mouse ESCs with mouse melanoma B16-F10 cells or mouse pancreatic tumor Pan02 cells, and found that ESCs significantly inhibited tumor cell proliferation. Coculture of ESCs and tumor cells resulted in significant inhibition of tumorigenesis in vivo. Histological analyses indicated that ESCs encircled apoptotic tumor cells. We carried out time course RNA-Seq analyses of ESC and tumor cell co-cultures, and identified Fas/FasL signaling as a major pathway involved in ESC-mediated apoptosis of tumor cells. We further generated FADD-deficient tumor cells by CRISPR/Cas9-mediated gene editing, and demonstrated that FADD-deficient tumor cells were obviously resistant to ESC-mediated inhibition of tumor cell proliferation. Our results indicate the Fas/FasL signaling pathway plays a critical role in ESCs-mediated tumoricidal activity.

PMID: 29218706 [PubMed - indexed for MEDLINE]
HDAC inhibitors restore BRAF-inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma.

Fetched: January 10th, 2019, 5:00am GMT

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HDAC inhibitors restore BRAF-inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma.

Int J Cancer. 2018 05 01;142(9):1926-1937

Authors: Gallagher SJ, Gunatilake D, Beaumont KA, Sharp DM, Tiffen JC, Heinemann A, Weninger W, Haass NK, Wilmott JS, Madore J, Ferguson PM, Rizos H, Hersey P

Abstract
Mutations in BRAF activate oncogenic MAPK signalling in almost half of cutaneous melanomas. Inhibitors of BRAF (BRAFi) and its target MEK are widely used to treat melanoma patients with BRAF mutations but unfortunately acquired resistance occurs in the majority of patients. Resistance results from mutations or non-genomic changes that either reactivate MAPK signalling or activate other pathways that provide alternate survival and growth signalling. Here, we show the histone deacetylase inhibitor (HDACi) panobinostat overcomes BRAFi resistance in melanoma, but this is dependent on the resistant cells showing a partial response to BRAFi treatment. Using patient- and in vivo-derived melanoma cell lines with acquired BRAFi resistance, we show that combined treatment with the BRAFi encorafenib and HDACi panobinostat in 2D and 3D culture systems synergistically induced caspase-dependent apoptotic cell death. Key changes induced by HDAC inhibition included decreased PI3K pathway activity associated with a reduction in the protein level of a number of receptor tyrosine kinases, and cell line dependent upregulation of pro-apoptotic BIM or NOXA together with reduced expression of anti-apoptotic proteins. Independent of these changes, panobinostat reduced c-Myc and pre-treatment of cells with siRNA against c-Myc reduced BRAFi/HDACi drug-induced cell death. These results suggest that a combination of HDAC and MAPK inhibitors may play a role in treatment of melanoma where the resistance mechanisms are due to activation of MAPK-independent pathways.

PMID: 29210065 [PubMed - indexed for MEDLINE]
Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

Fetched: January 10th, 2019, 5:00am GMT

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Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

Curr Eye Res. 2018 02;43(2):163-169

Authors: Brunner M, Steger B, Romano V, Hodson M, Zheng Y, Heimann H, Kaye SB

Abstract
PURPOSE: To evaluate indocyanine green angiography (ICGA) for the identification and characterization of afferent (feeding) and efferent (draining) vessels in patients with ocular surface neoplasia.
MATERIALS AND METHODS: Consecutive patients with biopsy-proven benign, pre-invasive, or invasive ocular surface tumors of the bulbar conjunctiva were included. Patients underwent anterior segment optical coherence tomography, ICGA, and color photography for the evaluation of the thickness, location, number, and diameter of afferent and efferent vessels of the lesions.
RESULTS: Twenty-two eyes of 22 patients with papillomas (n = 4), intra-epithelial neoplasia lesion (n = 2) in situ or invasive carcinomas (n = 6), nevus (n = 5), conjunctival melanocytic intra-epithelial neoplasia lesion (n = 1), and in situ or invasive melanomas (n = 4) were investigated. Afferent (feeder) vessels were identified in all lesions. There were fewer afferent (3.1 ± 1.6) than efferent (7.5 ± 3.5) vessels per lesion (p < 0.001) and the mean diameter was smaller for afferent (101 ± 62 μm, 28-281) than efferent vessels (137 ± 51 μm, 31-652; p = 0.017). The number of afferent and efferent vessels was associated with the thickness of the lesion (p = 0.037, p < 0.01). Lesion filling times differed between benign and invasive or pre-invasive lesions (p = 0.018).
CONCLUSIONS: ICGA is a useful adjunctive in vivo imaging method for the assessment of the vasculature in patients with suspected ocular surface neoplasia.

PMID: 29111820 [PubMed - indexed for MEDLINE]
The light bulb sign in pheochromocytoma.

Fetched: January 10th, 2019, 5:00am GMT

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The light bulb sign in pheochromocytoma.

Abdom Radiol (NY). 2017 Nov;42(11):2779

Authors: Fonseca EKUN, Ponte MPTR, Yamauchi FI, Baroni RH

PMID: 28580539 [PubMed - indexed for MEDLINE]