Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (464 unread)

Polyomavirus-driven Merkel cell carcinoma: Prospects for therapeutic vaccine development.

Fetched: March 30th, 2020, 5:00am GMT

Polyomavirus-driven Merkel cell carcinoma: Prospects for therapeutic vaccine development.

Mol Carcinog. 2020 Mar 27;:

Authors: Tabachnick-Cherny S, Pulliam T, Church C, Koelle DM, Nghiem P

Abstract
Great strides have been made in cancer immunotherapy including the breakthrough successes of anti-PD-(L)1 checkpoint inhibitors. In Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, PD-(L)1 blockade is highly effective. Yet, ~50% of patients either do not respond to therapy or develop PD-(L)1 refractory disease and, thus, do not experience long-term benefit. For these patients, additional or combination therapies are needed to augment immune responses that target and eliminate cancer cells. Therapeutic vaccines targeting tumor-associated antigens, mutated self-antigens, or immunogenic viral oncoproteins are currently being developed to augment T-cell responses. Approximately 80% of MCC cases in the United States are driven by the ongoing expression of viral T-antigen (T-Ag) oncoproteins from genomically integrated Merkel cell polyomavirus (MCPyV). Since T-Ag elicits specific B- and T-cell immune responses in most persons with virus-positive MCC (VP-MCC), and ongoing T-Ag expression is required to drive VP-MCC cell proliferation, therapeutic vaccination with T-Ag is a rational potential component of immunotherapy. Failure of the endogenous T-cell response to clear VP-MCC (allowing clinically evident tumors to arise) implies that therapeutic vaccination will need to be potent anśd synergize with other mechanisms to enhance T-cell activity against tumor cells. Here, we review the relevant underlying biology of VP-MCC, potentially applicable therapeutic vaccine platforms, and antigen delivery formats. We also describe early successes in the field of therapeutic cancer vaccines and address several clinical scenarios in which VP-MCC patients could potentially benefit from a therapeutic vaccine.

PMID: 32219902 [PubMed - as supplied by publisher]

Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis.

Fetched: March 29th, 2020, 5:00am GMT

Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis.

Radiother Oncol. 2019 05;134:211-219

Authors: Petrelli F, Ghidini A, Torchio M, Prinzi N, Trevisan F, Dallera P, De Stefani A, Russo A, Vitali E, Bruschieri L, Costanzo A, Seghezzi S, Ghidini M, Varricchio A, Cabiddu M, Barni S, de Braud F, Pusceddu S

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with a high propensity for local recurrence and regional and distant metastases. The main treatment is surgery with narrow excision margins and draining nodes, plus or minus adjuvant radiotherapy (RT) on the surgical bed and/or lymph nodes. We performed a systematic review and meta-analysis of the benefits of adjuvant RT in MCC treatment. PubMed, EMBASE, and the Cochrane Library were systematically searched to identify relevant studies published before September 2018. Prospective trials and retrospective series comparing adjuvant RT vs. no RT in resected primary MCCs were included. Primary endpoint was to evaluate the outcomes of MCC patients who received adjuvant RT in term of overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) for OS and DFS were aggregated according to a fixed or random effect model. Secondary endpoints were local, locoregional, and distant DFS. A total of 17,179 MCCs across 29 studies were analysed. There was a significant difference in OS between the RT and no RT arms (HR = 0.81, 95%CI 0.75-0.86, P < 0.001). There was also a significant difference in DFS in favour of adjuvant RT (HR = 0.45, 95%CI 0.32-0.62, P < 0.001). Adjuvant RT improved locoregional DFS and local DFS but not distant DFS (HR = 0.3, 95%CI 0.22-0.42; HR = 0.21, 95%CI 0.14-0.33, and HR = 0.79, 95%CI 0.49-1.14, respectively). Meta-regression analysis showed that high Newcastle-Ottawa scale scores, stage I-II MCCs, shorter follow-up durations, size >2 cm, and being of a younger age were associated with increased OS. This systematic review and meta-analysis suggests a survival and DFS benefit for postoperative radiation of MCCs. Intermediate stage MCCs derive the maximum benefit with local and regional relapses reduced by 80% and 70%, respectively. Conversely, distant metastases were not significantly prevented.

PMID: 31005218 [PubMed - indexed for MEDLINE]

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Fetched: March 28th, 2020, 5:00am GMT

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Immunotherapy. 2020 Mar 24;:

Authors: Ascierto PA, Garbe C

Abstract
Over the last few years, extensive research has improved our understanding of tumor immunology and has enabled the development of novel treatments. The state of the art of immunotherapy in various types of malignancies was exhaustively discussed in the 'Immunotherapy bridge' meeting, which was held in Naples on 4-5 December 2019. Highlights related to the immunological treatment of nonmelanoma skin cancer are the content of this article.

PMID: 32208790 [PubMed - as supplied by publisher]

Immunologic Characteristics of Nonmelanoma Skin Cancers: Implications for Immunotherapy.

Fetched: March 26th, 2020, 5:01am GMT

Immunologic Characteristics of Nonmelanoma Skin Cancers: Implications for Immunotherapy.

Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-10

Authors: Hall ET, Fernandez-Lopez E, Silk AW, Dummer R, Bhatia S

Abstract
In this review, we summarize the immunology of nonmelanoma skin cancers (NMSCs) and the clinical data with immunotherapy in this heterogeneous group of cancers that include basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), and Merkel cell carcinoma (MCC). NMSCs are exceedingly common, and their treatment consumes substantial health care resources. Annual global mortality from NMSCs is comparable to that from malignant melanoma. Although the majority of NMSCs are localized at diagnosis and are treated effectively with surgery, metastases (nodal and distant) can sometimes arise and require systemic therapy. Given the success of immunotherapy in treating cutaneous melanoma, there has been an increasing interest in studying the immunology of NMSCs. Immunocompromised patients have a substantially higher risk of developing NMSCs (particularly CSCC and MCC), suggesting a role of the immune system in the pathogenesis of these cancers. Similar to cutaneous melanoma, the pathogenesis of BCC, CSCC, and virus-negative MCC is related to DNA damage from ultraviolet radiation exposure, and these cancers have a very high tumor mutational burden, which likely results in higher levels of tumor neoantigens that may be targets for the immune system. Viral antigens in virus-positive MCC are also strongly immunogenic. Emerging data from clinical trials of immune checkpoint inhibitors in NMSCs look very promising and are rapidly changing the treatment landscape of these cancers. Specifically, pembrolizumab and avelumab are U.S. Food and Drug Administration-approved for treatment of metastatic MCC and cemiplimab for metastatic CSCC. Several ongoing trials are investigating novel immunotherapies (monotherapies as well as combination) for treatment of NMSCs.

PMID: 32207669 [PubMed - in process]

The Obesity-Related Gut Bacterial and Viral Dysbiosis Can Impact the Risk of Colon Cancer Development.

Fetched: March 26th, 2020, 5:01am GMT

The Obesity-Related Gut Bacterial and Viral Dysbiosis Can Impact the Risk of Colon Cancer Development.

Microorganisms. 2020 Mar 19;8(3):

Authors: Campisciano G, de Manzini N, Delbue S, Cason C, Cosola D, Basile G, Ferrante P, Comar M, Palmisano S

Abstract
An incorrect food regimen from childhood is suggested to negatively impact the gut microbiome composition leading to obesity and perhaps to colon rectal cancer (CRC) in adults. In this study, we show that the obesity and cancer gut microbiota share a characteristic microbial profile with a high colonization by mucin degraders species, such as Hafnia alvei and Akkermansia muciniphila. In addition, the species Clostridium bolteae, a bacterium associated with insulin resistance, dyslipidemia, and inflammation, has been associated with the presence of oncogenic Human Polyomaviruses (HPyVs). Merkel cell Polyomavirus (MCPyV) and BK Polyomavirus (BKPyV) were the most frequently oncogenic viruses recovered in the gut of both obese and tumor patients. Considering the high seroprevalence of HPyVs in childhood, their association with specific bacterial species deserve to be further investigated. Data from the present study highlight the presence of a similar microbiome pattern in CRC and obese subjects, suggesting that obese microbiome may represent an opportunity for tumorigenic/driver bacteria and viruses to trigger cell transformation.

PMID: 32204328 [PubMed]

Prognostic Significance of "Nonsolid" Microscopic Metastasis in Merkel Cell Carcinoma Sentinel Lymph Nodes.

Fetched: March 25th, 2020, 5:01am GMT

Prognostic Significance of "Nonsolid" Microscopic Metastasis in Merkel Cell Carcinoma Sentinel Lymph Nodes.

Am J Surg Pathol. 2019 07;43(7):907-919

Authors: Erstine EM, Tetzlaff MT, Jia X, Aung PP, Prieto VG, Funchain P, Gastman BR, Billings SD, Ko JS

Abstract
Our recent work regarding Merkel cell carcinoma sentinel lymph node (SLN) metastasis found that "solid" pattern microscopic metastasis conferred worse prognosis than the "nonsolid" ones. The goals of the present study were to (1) compare the prognostic significance/outcomes of 2 diagnostic groups-patients with a nonsolid pattern of SLN metastasis and those with diagnostically negative SLN biopsies (SLNB), and (2) evaluate the durability of SLN metastasis after extensive sectioning. Five-level, step-wise sectioning at 250-μm intervals was performed in all SLN blocks with an immunohistochemical stain for CK20 on all levels. The presence and pattern of metastases were recorded and analyzed as were corresponding patient and tumor parameters. Median follow-up durations for all patients (n=38), positive SLNB (n=16) and negative SLNB (n=22) groups were 56.3, 50.4, and 66.8 months, respectively. Overall survival (OS) and disease-specific survival (DSS) did not differ between the 2 diagnostic groups (OS P=0.65, DSS P=0.37) but did differ by immune status (immunocompetent vs. immunosuppressed, OS P=0.03, DSS P=0.005) and primary tumor category (OS P<0.0001, DSS P=0.001). On deeper sectioning, all 16 diagnostically positive SLNB continued to show nonsolid microscopic metastasis, and 32% (7/22) diagnostically negative SLNB revealed nonsolid metastasis. DSS was worse for sinusoidal-pattern metastasis versus all others (P=0.02). Five of 38 patients (13%) died of disease; the only immunocompetent patient had sinusoidal-pattern metastasis discovered in a diagnostically negative SLNB. Our data suggest that outcome for nonsolid metastasis is similar to that of negative SLNB with the exception of the sinusoidal pattern, which was associated with worse outcome. Larger studies are warranted to quantify and compare microscopic metastatic tumor burden by pattern and confirm whether the sinusoidal pattern confers an intermediate prognostic risk between solid and other nonsolid microscopic metastases.

PMID: 31094923 [PubMed - indexed for MEDLINE]

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

Fetched: March 21st, 2020, 5:01am GMT

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

Genome Med. 2020 Mar 18;12(1):30

Authors: Starrett GJ, Thakuria M, Chen T, Marcelus C, Cheng J, Nomburg J, Thorner AR, Slevin MK, Powers W, Burns RT, Perry C, Piris A, Kuo FC, Rabinowits G, Giobbie-Hurder A, MacConaill LE, DeCaprio JA

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin caused by either the integration of Merkel cell polyomavirus (MCPyV) and expression of viral T antigens or by ultraviolet-induced damage to the tumor genome from excessive sunlight exposure. An increasing number of deep sequencing studies of MCC have identified significant differences between the number and types of point mutations, copy number alterations, and structural variants between virus-positive and virus-negative tumors. However, it has been challenging to reliably distinguish between virus positive and UV damaged MCC.
METHODS: In this study, we assembled a cohort of 71 MCC patients and performed deep sequencing with OncoPanel, a clinically implemented, next-generation sequencing assay targeting over 400 cancer-associated genes. To improve the accuracy and sensitivity for virus detection compared to traditional PCR and IHC methods, we developed a hybrid capture baitset against the entire MCPyV genome and software to detect integration sites and structure.
RESULTS: Sequencing from this approach revealed distinct integration junctions in the tumor genome and generated assemblies that strongly support a model of microhomology-initiated hybrid, virus-host, circular DNA intermediate that promotes focal amplification of host and viral DNA. Using the clear delineation between virus-positive and virus-negative tumors from this method, we identified recurrent somatic alterations common across MCC and alterations specific to each class of tumor, associated with differences in overall survival. Finally, comparing the molecular and clinical data from these patients revealed a surprising association of immunosuppression with virus-negative MCC and significantly shortened overall survival.
CONCLUSIONS: These results demonstrate the value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC. Furthermore, integrating these data with clinical data revealed features that could impact patient outcome and improve our understanding of MCC risk factors.

PMID: 32188490 [PubMed - in process]

miRNAs in the Diagnosis and Prognosis of Skin Cancer.

Fetched: March 20th, 2020, 5:00am GMT

miRNAs in the Diagnosis and Prognosis of Skin Cancer.

Front Cell Dev Biol. 2020;8:71

Authors: Neagu M, Constantin C, Cretoiu SM, Zurac S

Abstract
Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets.

PMID: 32185171 [PubMed]

Prevalent and diverse intratumoral oncoprotein-specific CD8+ T cells within polyoma virus-driven Merkel cell carcinomas.

Fetched: March 19th, 2020, 5:00am GMT

Prevalent and diverse intratumoral oncoprotein-specific CD8+ T cells within polyoma virus-driven Merkel cell carcinomas.

Cancer Immunol Res. 2020 Mar 16;:

Authors: Jing L, Ott M, Church CD, Kulikauskas RM, Ibrani D, Iyer JG, Afanasiev OK, Colunga A, Cook MM, Xie H, Greninger AL, Paulson KG, Chapuis AG, Bhatia S, Nghiem P, Koelle DM

Abstract
Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AAs). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag-specific T cells. Strategies to increase CD8+ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TILs) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DCs). TILs from 9 of 12 (75%) subjects contained CD8+ T cells recognizing 1-8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8+ TIL epitopes and prior TIL data indicated that 97% of MCPyV+ MCC patients had HLA alleles with the genetic potential that restrict CD8+ T-cell responses to MCPyV T-Ag. The LT AA 70-110 region was epitope-rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag-expressing DCs was documented. Recovery of MCPyV oncoprotein-specific CD8+ TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicate that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.

PMID: 32179557 [PubMed - as supplied by publisher]

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm.

Fetched: March 19th, 2020, 5:00am GMT

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm.

Blood Adv. 2020 Mar 24;4(6):1006-1011

Authors: Nomburg J, Bullman S, Chung SS, Togami K, Walker MA, Griffin GK, Morgan EA, LeBoeuf NR, DeCaprio JA, Meyerson M, Lane AA

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy believed to originate from plasmacytoid dendritic cells (pDCs), the immune cells responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous infiltration occupying the dermis and subcutis. One half of patients present with BPDCN cells only in the skin, with no evidence of disease elsewhere. Because normal pDCs are rare or absent in cutaneous sites, and they only traffic to the skin after activation by pathogen or inflammation, our aim was to determine if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma (CTCL) and normal skin as controls. GATK-PathSeq was used to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID (Viral Identification and Discovery; [https:] for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma, human papillomavirus in head and neck squamous cell carcinoma, and Kaposi's sarcoma herpesvirus in Kaposi's sarcoma in a blinded fashion. Thus, at the level of sensitivity used here, we found no clear pathogen linked to BPDCN.

PMID: 32182365 [PubMed - in process]

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.

Fetched: March 19th, 2020, 5:00am GMT

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.

Front Cell Dev Biol. 2020;8:47

Authors: Vescovo T, Pagni B, Piacentini M, Fimia GM, Antonioli M

Abstract
About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers.

PMID: 32181249 [PubMed]

Permalink for 'Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.'

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.

Fetched: March 18th, 2020, 5:00am GMT

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.

Am J Dermatopathol. 2019 Nov;41(11):819-825

Authors: Walsh NM, Castonguay MC, Carter MD, Pasternak S, Ly TY, Doucette S, Hanly JG, Saggini A, Cerroni L

Abstract
We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

PMID: 31634167 [PubMed - indexed for MEDLINE]

Co-occurrence of Merkel Cell Carcinoma and Chronic Inflammatory Demyelinating Polyneuropathy.

Fetched: March 13th, 2020, 5:00am GMT

Co-occurrence of Merkel Cell Carcinoma and Chronic Inflammatory Demyelinating Polyneuropathy.

JAMA Dermatol. 2020 Mar 11;:

Authors: Kuo AM, Barker CA

PMID: 32159728 [PubMed - as supplied by publisher]

Permalink for 'The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.'

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Fetched: March 13th, 2020, 5:00am GMT

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Antioxidants (Basel). 2020 Mar 07;9(3):

Authors: Chaouni S, Lecomte DD, Stefan D, Leduc A, Barraux V, Leconte A, Grellard JM, Habrand JL, Guillamin M, Sichel F, Laurent C

Abstract
Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer). To try to discriminate these 2 groups, biomarkers of interest were measured on the different blood compartments after ex vivo irradiation. In lymphocytes, cell cycle, apoptosis and genotoxicity were studied. Oxidative stress was evaluated by the determination of the erythrocyte antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, reduced and oxidized glutathione) as well as degradation products (protein carbonylation, lipid peroxidation). Inflammation was assessed in the plasma by the measurement of 14 cytokines. The most radiosensitive patients presented a decrease in apoptosis, micronucleus frequency, antioxidant enzyme activities, glutathione and carbonyls; and an increase in TNF-a (Tumor Necrosis Factor a), IL-8 (Interleukin 8) and TGF-β1 (Transforming Growth Factor β1) levels. These findings have to be confirmed on a higher number of patients and before radiotherapy and could allow to predict the occurrence of late skin side effects after radiotherapy.

PMID: 32156042 [PubMed]

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Fetched: March 13th, 2020, 5:00am GMT

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Klin Onkol. 2019;32(Supplementum 3):72-77

Authors: Brychtová V, Hrabal V, Vojtěšek B

Abstract
BACKGROUND: Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor. Viral proteins functionally inactivate p53 and deregulate the expression of proteins active during apoptosis, cell proliferation and DNA damage response. Hepatitis virus B HbX protein and hepatitis virus C proteins NS2 and NS5A interact with p53 and prevent its localisation to the nucleus and thus reduce its transcriptional activity. Another mechanism lies in elevated p53 degradation caused by the BZLF1 protein of the Epstein-Barr virus, the LANA protein of the Kaposi sarcoma virus and human papilloma virus E6. The Merkel cell polyomavirus large T antigen does not interact directly with p53, however it acts through downregulation of p53 mediated transcription. The tax protein of human T cell lymphotropic virus type 1 modifies p53 posttranslationally and thus blocks its interaction with other factors of transcription machinery. Due to its tumour suppressor function and role in the maintenance of the genome integrity, the p53 protein is one of the best studied proteins. Following this, evolutionary homologues with important developmental functions p63 and p73 are intensively studied as well. Their roles in oncogenesis have not been clarified yet.
PURPOSE: This review describes some of their known interactions with oncogenic viral proteins.

PMID: 31627709 [PubMed - indexed for MEDLINE]

Permalink for 'A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.'

A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.

Fetched: March 12th, 2020, 5:00am GMT

A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.

J Exp Clin Cancer Res. 2019 Oct 22;38(1):424

Authors: Cappabianca L, Guadagni S, Maccarone R, Sebastiano M, Chiominto A, Farina AR, Mackay AR

Abstract
BACKGROUND: Merkel cell carcinomas (MCCs) are rare, aggressive, therapeutically-challenging skin tumours that are increasing in incidence and have poor survival rates. The majority are caused by genomic Merkel cell polyomavirus (MCPyV) integration and MCPyV T-antigen expression. Recently, a potential oncogenic role for the tropomyosin-related tyrosine kinase A receptor (TrkA) has been proposed in MCC. Alternative TrkAIII splicing is a TrkA oncogenic activation mechanism that can be promoted by SV40 large T-antigen, an analogue of MCPyV large T-antigen. In this pilot study, therefore, we have evaluated TrkAIII splicing as a novel potential oncogenic mechanism and therapeutic target in MCPyV positive MCC.
METHODS: Formalin-fixed paraffin-embedded MCC tissues, consisting of 10 stage IV, 1 stage IIIB, 1 stage IIB, 4 stage IIA and 2 stage I tumours, from patients diagnosed and treated from September 2006 to March, 2019, at the University of L'Aquila, L'Aquila, Italy, were compared to 3 primary basal cell carcinomas (BCCs), 3 primary squamous cell carcinomas (SCCs) and 2 normal skin samples by RT-PCR for MCPyV large T-antigen, small T-antigen, VP-1 expression and alternative TrkAIII splicing and by indirect IF for evidence of intracellular TrkA isoform expression and activation.
RESULTS: 9 of 10 Recurrent stage IV MCCs were from patients (P.1-3) treated with surgery plus loco-regional Melphalan chemotherapy and remaining MMCs, including 1 stage IV tumour, were from patients treated with surgery alone (P. 4-11). All MCPyV positive MCCs exhibiting MCPyV large T-antigen expression (17 of 18MCCs, 90%) exhibited alternative TrkAIII mRNA splicing (100%), which was exclusive in a significant number and predominant (> 50%) in all stage IV MCCs and the majority of stage 1-III MCCs. MCCs with higher TrkAIII to 18S rRNA expression ratios also exhibited strong or intermediate immunoreactivity to anti-TrkA antibodies, consistent with cytoplasmic TrkAIII expression and activation. In contrast, the MCPyV negative MCC, BCCs, SCCs and normal skin tissues all exhibited exclusive fully-spliced TrkA mRNA expression, associated with variable immunoreactivity for non-phosphorylated but not phosphorylated TrkA.
CONCLUSIONS: MCPyV positive MCCs but not MCPyV negative MCC, BCCs and SCCs exhibit predominant alternative TrkAIII splicing, with evidence of intracellular TrkAIII activation. This establishes a new potential MCC subset, unveils a novel potential MCPyV oncogenic mechanism and identifies TrkAIII as a novel potential therapeutic target in MCPyV positive MCC.

PMID: 31640749 [PubMed - indexed for MEDLINE]

Permalink for 'Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.'

Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.

Fetched: March 11th, 2020, 5:00am GMT

Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.

Br J Dermatol. 2020 Mar 09;:

Authors: Song Y, Zheng C, Shannon AB, Fraker DL, Miura JT, Karakousis GC

Abstract
Merkel cell carcinoma (MCC), a neuroendocrine cutaneous malignancy, may be especially aggressive in immunocompromised patients.1,2 Factors associated with sentinel lymph node (SLN) involvement and overall survival (OS) have been described for the general population with clinically-localized MCC, but prognostic factors in immunosuppressed patients have not been well characterized.3,4 The study objectives were to identify characteristics associated with SLN status and OS in this patient population.

PMID: 32147810 [PubMed - as supplied by publisher]

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms.

Fetched: March 8th, 2020, 5:00am GMT

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms.

Cell Oncol (Dordr). 2020 Mar 05;:

Authors: Blessin NC, Spriestersbach P, Li W, Mandelkow T, Dum D, Simon R, Hube-Magg C, Lutz F, Viehweger F, Lennartz M, Fraune C, Nickelsen V, Fehrle W, Göbel C, Weidemann S, Clauditz T, Lebok P, Möller K, Steurer S, Izbicki JR, Sauter G, Minner S, Jacobsen F, Luebke AM, Büscheck F, Höflmayer D, Wilczak W, Burandt E, Hinsch A

Abstract
PURPOSE: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes.
METHODS: The density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides.
RESULTS: We found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin's lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin's lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved.
CONCLUSION: These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

PMID: 32141029 [PubMed - as supplied by publisher]

Permalink for 'TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.'

TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.

Fetched: March 7th, 2020, 5:00am GMT

TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.

Am J Clin Pathol. 2020 Mar 05;:

Authors: Hoang MP, Donizy P, Wu CL, Kopczynski J, Pieniazek M, Miller DM, Ryś J

Abstract
OBJECTIVES: Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the prognostic potential of B-cell markers (terminal deoxynucleotidyl transferase [TdT], PAX5, CD117), follicular stem cell markers (CK15, CK19), p63, p53, RB, and Merkel cell polyomavirus (MCPyV; CM2B4) in 136 primary cutaneous Merkel cell carcinomas.
METHODS: Clinical, histopathologic, and immunohistochemical analyses were performed. The results were correlated with patient outcomes by Fisher exact test, log-rank tests, and Cox multivariate models.
RESULTS: By Fisher exact test, although TdT significantly correlated with both lack of progression (P = .0087) and alive status (P = .0056), MCPyV status correlated only with alive status (P = .031). In univariate analyses, TdT, MCPyV, and RB significantly correlated with improved overall survival, whereas p63 and CK15 correlated with worse overall survival. However, in multivariate analyses, only TdT expression remained as an independent predictor of improved overall survival, Merkel cell carcinoma-specific survival, and progression-free survival. By linear regression analyses, significant correlations between MCPyV vs TdT, PAX5, and CD117 were observed.
CONCLUSIONS: TdT expression is a potential marker of better survival in Merkel cell carcinoma. Expression of B-cell markers is associated with MCPyV, suggesting that clonal viral integration might play a role in the expression of these markers.

PMID: 32134459 [PubMed - as supplied by publisher]

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

Fetched: March 6th, 2020, 5:01am GMT

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

Thorac Cancer. 2019 03;10(3):445-451

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 - indexed for MEDLINE]

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

Fetched: March 5th, 2020, 5:01am GMT

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

Cancers (Basel). 2020 Feb 28;12(3):

Authors: Naseri S, Steiniche T, Ladekarl M, Bønnelykke-Behrndtz ML, Hölmich LR, Langer SW, Venzo A, Tabaksblat E, Klausen S, Skaarup Larsen M, Junker N, Chakera AH

Abstract
Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.

PMID: 32121063 [PubMed]

Systematic review of sentinel lymph node biopsy in Merkel cell carcinoma of the head and neck.

Fetched: March 5th, 2020, 5:01am GMT

Systematic review of sentinel lymph node biopsy in Merkel cell carcinoma of the head and neck.

Head Neck. 2018 12;40(12):2704-2713

Authors: Karunaratne YG, Gunaratne DA, Veness MJ

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor arising on the head and neck in 40%-50% of patients. Between 20% and 40% will harbor subclinical nodal metastasis.
METHODS: Using search terms 'Merkel AND sentinel', MEDLINE, PUMED, and EMBASE databases were systematically reviewed for publications regarding sentinel lymph node biopsy (SLNB) in classification I and II MCC of the head and neck.
RESULTS: Twenty-nine publications encompassing 136 patients were included. The SLNB finding was positive in 42 patients (30.9%). Primary MCC was located on the malar/zygomatic (34.4%), forehead/frontal (13.5%), and nasal (13.5%) regions. Recurrence in an SLNB negative nodal basin result occurred in 10 patients (false negative rate of 19.2%). Site of primary MCC was not associated with a false-negative SLNB result; however, there was a non-statistically significant trend for increased frequency among midline lesions.
CONCLUSIONS: Sentinel lymph node biopsy (SLNB) is recommended for eligible patients with classification I and II head and neck MCC.

PMID: 29934958 [PubMed - indexed for MEDLINE]

DETECTing Merkel Cell Polyomavirus in Merkel Tumors.

Fetched: March 4th, 2020, 5:00am GMT

DETECTing Merkel Cell Polyomavirus in Merkel Tumors.

Front Mol Biosci. 2020;7:10

Authors: Arora R, Gupta K, Vijaykumar A, Krishna S

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post-integration (~80% cases), or by UV-mediated DNA damage. Interestingly, overall survival of MCV-positive Merkel cell carcinoma patients is better, making this differential information of significant diagnostic and prognostic value. Also, MCV provides a direct target for therapy in MCC patients. Currently, the methods used for diagnosis of MCV in tumors are often discordant and unreliable. Here we used a guided molecular scissors based-DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) technique to develop an in vitro molecular diagnostic tool for MCV-positive MCC. DETECTR couples recombinase polymerase based amplification of target MCV DNA with Cas12a mediated detection. CRISPR diagnostics couple specific detection followed by cutting of the pathogenic DNA by the Cas enzyme-gRNA complex, with non-specific cutting of ssDNA that provides a measurable visual cue. To detect MCV DNA in MCC, we designed Cas12a gRNAs targeting the MCV DNA and tested their targeting efficiency, and sensitivity using a fluorophore quencher labeled reporter assay. We show that MCV DETECTR system can detect MCV integrated in Merkel tumor rapidly, specifically and with femto-molar sensitivity. Our study is a preliminary, proof-of-principle analysis showing the use of CRISPR for MCV diagnosis. Further validation in human tumor samples is needed for its clinical use in the near future. This new system is promising and we hope it can be coupled with immunohistochemical studies to diagnose the viral status of MCC in clinics soon.

PMID: 32118036 [PubMed]

Mathematical oncology and it's application in non melanoma skin cancer - A primer for radiation oncology professionals.

Fetched: March 1st, 2020, 5:00am GMT

Mathematical oncology and it's application in non melanoma skin cancer - A primer for radiation oncology professionals.

Oral Oncol. 2020 Feb 25;103:104473

Authors: Aherne NJ, Dhawan A, Scott JG, Enderling H

Abstract
Cancers of the skin (the majority of which are basal and squamous cell skin carcinomas, but also include the rarer Merkel cell carcinoma) are overwhelmingly the most common of all types of cancer. Most of these are treated surgically, with radiation reserved for those patients with high risk features or anatomical locations less suitable for surgery. Given the high incidence of both basal and squamous cell carcinomas, as well as the relatively poor outcome for Merkel cell carcinoma, it is useful to investigate the role of other disciplines regarding their diagnosis, staging and treatment. Mathematical modelling is one such area of investigation. The use of mathematical modelling is a relatively recent addition to the armamentarium of cancer treatment. It has long been recognised that tumour growth and treatment response is a complex, non-linear biological phenomenon with many mechanisms yet to be understood. Despite decades of research, including clinical, population and basic science approaches, we continue to be challenged by the complexity, heterogeneity and adaptability of tumours, both in individual patients in the oncology clinic and across wider patient populations. Prospective clinical trials predominantly focus on average outcome, with little understanding as to why individual patients may or may not respond. The use of mathematical models may lead to a greater understanding of tumour initiation, growth dynamics and treatment response.

PMID: 32109841 [PubMed - as supplied by publisher]

Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma.

Fetched: March 1st, 2020, 5:00am GMT

Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma.

Cancers (Basel). 2020 Feb 25;12(3):

Authors: Fan K, Zebisch A, Horny K, Schrama D, Becker JC

Abstract
miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established. Nearly complete miR-375 knockdown in MCC cell lines was achieved using antagomiRs via nucleofection. The cell viability, growth characteristics, and morphology were not altered by this knockdown. miR-375 target genes and related signaling pathways were determined using Encyclopedia of RNA Interactomes (ENCORI) revealing Hippo signaling and epithelial to mesenchymal transition (EMT)-related genes likely to be regulated. Therefore, their expression was analyzed by multiplexed qRT-PCR after miR-375 knockdown, demonstrating only a limited change in expression. In summary, highly effective miR-375 knockdown in classical MCC cell lines did not significantly change the cell viability, morphology, or oncogenic signaling pathways. These observations render miR-375 an unlikely intracellular oncogene in MCC cells, thus suggesting that likely functions of miR-375 for the intercellular communication of MCC should be addressed.

PMID: 32106526 [PubMed]

Product review: avelumab, an anti-PD-L1 antibody.

Fetched: March 1st, 2020, 5:00am GMT

Product review: avelumab, an anti-PD-L1 antibody.

Hum Vaccin Immunother. 2019;15(4):891-908

Authors: Collins JM, Gulley JL

Abstract
Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types. Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen. Its acceptable safety profile and ability to induce durable responses in otherwise deadly tumors provide the rationale for its use in other tumor types and in combination with other therapies.

PMID: 30481100 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

Fetched: February 29th, 2020, 5:00am GMT

Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

Ann Surg Oncol. 2020 Feb 26;:

Authors: Farley CR, Perez MC, Soelling SJ, Delman KA, Harit A, Wuthrick EJ, Messina JL, Sondak VK, Zager JS, Lowe MC

Abstract
INTRODUCTION: The eighth edition of the American Joint Committee on Cancer (AJCC8) Staging Manual provides important information for staging and prognostication; however, survival estimates for patients with Stage I-III Merkel cell carcinoma (MCC), a rare disease, may be as practical using data from large-volume centers as that collated for the AJCC analysis. As such, we compared our institutional outcomes to AJCC8.
METHODS: Patients who presented from 2005 to 2017 with MCC to two high-volume centers were included. Demographics, clinicopathologic characteristics, survival and recurrence data were compiled, and outcomes compared to AJCC8.
RESULTS: A total of 409 patients were included. Median age was 75 (range 29-98) years, and 68% were male. Median follow-up was 16 months (0-157). Five-year overall survival (OS) was 70%; 5-year disease-specific survival (DSS) was 84%. When stratified by extent of disease, 5-year OS was higher for patients with local disease compared to those with nodal disease (72.6% vs 62.7%, p=0.005). Similarly, patients with local disease had higher 5-year DSS than those with nodal disease (90.1% vs 76.8%, p=0.002). Five-year recurrence-free survival was 59.2% for all patients, 65.0% for local disease and 48.3% for nodal disease (p=0.033).
CONCLUSIONS: Here, MCC patients with local or nodal disease have substantially higher OS rates than predicted in AJCC8 (5-year: 72.6% vs 50.6%; 62.7% vs 35.4%, respectively). Importantly, 5-year DSS was significantly better than the OS rates reported presently and in AJCC8. As clinicians and patients rely on AJCC to accurately prognosticate and guide treatment decisions, these estimates should be reassessed and updated to more accurately predict survival outcomes.

PMID: 32103415 [PubMed - as supplied by publisher]

Lethal thrombocytopenia in a patient treated with avelumab for metastatic Merkel cell carcinoma.

Fetched: February 28th, 2020, 5:01am GMT

Lethal thrombocytopenia in a patient treated with avelumab for metastatic Merkel cell carcinoma.

J Dtsch Dermatol Ges. 2019 Jan;17(1):73-75

Authors: Kratzsch D, Simon JC, Pönitzsch I, Ziemer M

PMID: 30549433 [PubMed - indexed for MEDLINE]

Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity.

Fetched: February 27th, 2020, 5:01am GMT

Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity.

Biology (Basel). 2020 Feb 19;9(2):

Authors: Liu W, Krump NA, Herlyn M, You J

Abstract
Merkel cell carcinoma (MCC) is a highly lethal skin cancer. MCC tumors rapidly develop resistance to the chemotherapies tested to date. While PD-1/PD-L1 immune checkpoint blockade has demonstrated success in MCC treatment, a significant portion of MCC patients are nonresponsive. Therefore, the pressing need for effective MCC chemotherapies remains. We screened a library of natural products and discovered that one compound, glaucarubin, potently reduced the viability of Merkel cell polyomavirus (MCPyV)-positive MCCs, while remaining nontoxic to primary human fibroblasts and MCPyV-negative MCC cell lines tested. Protein array and Western blot analyses revealed that glaucarubin induces DNA damage and PARP-1 cleavage that correlates with the loss of viability in MCC cells. However, high basal expression of the antiapoptotic factor BCL-2 allowed a subpopulation of cells to survive glaucarubin treatment. Previous studies have shown that, while targeting BCL-2 family proteins significantly decreases MCC cell viability, BCL-2 antisense therapy alone was insufficient to inhibit tumor growth in patients with advanced MCC. We discovered that treatment with an FDA-approved BCL-2 inhibitor in the context of glaucarubin-induced DNA damage led to near complete killing in multiple MCPyV-positive MCC cell lines that express high levels of BCL-2. The combination of DNA damage-induced apoptosis and BCL-2 inhibition thus represents a novel therapeutic strategy for MCPyV-positive MCCs.

PMID: 32093022 [PubMed]

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

Fetched: February 26th, 2020, 5:00am GMT

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

J Dtsch Dermatol Ges. 2019 May;17(5):562-576

Authors: Becker JC, Eigentler T, Frerich B, Gambichler T, Grabbe S, Höller U, Klumpp B, Loquai C, Krause-Bergmann A, Müller-Richter U, Pföhler C, Schneider-Burrus S, Stang A, Terheyden P, Ugurel S, Veith J, Mauch C

Abstract
Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD-1/PD-L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.

PMID: 31056838 [PubMed - indexed for MEDLINE]

VEGF-A Inhibition as a Potential Therapeutic Approach in Merkel Cell Carcinoma.

Fetched: February 26th, 2020, 5:00am GMT

VEGF-A Inhibition as a Potential Therapeutic Approach in Merkel Cell Carcinoma.

J Invest Dermatol. 2019 03;139(3):736-739

Authors: Kervarrec T, Gaboriaud P, Tallet A, Leblond V, Arnold F, Berthon P, Schweinitzer S, Larcher T, Guyétant S, Schrama D, Houben R, Samimi M, Touzé A

PMID: 30359576 [PubMed - indexed for MEDLINE]

Completion lymph node dissection for merkel cell carcinoma.

Fetched: February 25th, 2020, 5:00am GMT

Completion lymph node dissection for merkel cell carcinoma.

Am J Surg. 2020 Feb 15;:

Authors: Cramer JD, Suresh K, Sridharan S

Abstract
BACKGROUND: Sentinel lymph node biopsy (SLNB) is widely used for Merkel cell carcinoma (MCC), however in SLNB positive MCC the role of completion lymph node dissection (CLND) with or without adjuvant radiation therapy is unclear.
OBJECTIVE: Our goal was to determine the impact of CLND and adjuvant radiation therapy on survival in SLNB positive MCC.
MATERIALS AND METHODS: We examined 447 patients with MCC with a positive SLNB in the National Cancer Data Base from 2012 to 2015. We compared patients who underwent CLND versus observation with or without adjuvant radiation.
RESULTS: Compared with CLND and adjuvant radiation (reference) treatment with observation (HR 3.54, CI 1.36-9.18) or CLND alone (HR 2.54, CI 1.03-6.27) were associated with worse overall survival after adjusting for clinicopathologic differences. In contrast treatment with adjuvant radiation alone without CLND was not associated with worse overall survival (HR 1.70, CI 0.74-3.92) compared with CLND and adjuvant radiation (reference).
CONCLUSIONS: In SLNB positive MCC, CLND alone is associated with worse survival compared with treatment with adjuvant radiation or both CLND and adjuvant radiation.

PMID: 32087988 [PubMed - as supplied by publisher]

Landscape of current and future therapies of Merkel cell carcinoma.

Fetched: February 23rd, 2020, 5:01am GMT

Landscape of current and future therapies of Merkel cell carcinoma.

Dermatol Ther. 2020 Feb 21;:e13281

Authors: Kwiatkowska D, Reich A

Abstract
Merkel cell carcinoma is rare and aggressive skin cancer, which occurrence is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus. In recent years, significant progress in understanding the mechanism of Merkel cell carcinoma pathogenesis has been observed. This neoplasm often expresses PD-L1, and MCPyV-specific T-cells can express PD-1 thus PD-1 / PD-L1 checkpoint therapies seem to be remarkably interesting treatment options. Many clinical trials are currently being conducted to confirm their effectiveness and safety for this group of patients. However, only about half of advanced Merkel cell carcinoma patients could achieve remission or disease stabilization through PD-1 / PD-L1 checkpoint therapies thus innovative treatments are still needed. In this paper, we have presented current and future directions in the development of Merkel cell carcinoma therapy. This article is protected by copyright. All rights reserved.

PMID: 32083780 [PubMed - as supplied by publisher]

Electrochemotherapy With Intravenous Bleomycin in the Treatment of Unresectable Merkel Cell Carcinoma.

Fetched: February 23rd, 2020, 5:01am GMT

Electrochemotherapy With Intravenous Bleomycin in the Treatment of Unresectable Merkel Cell Carcinoma.

Actas Dermosifiliogr. 2019 Oct;110(8):687-688

Authors: Padilla-España L, Toledo-Pastrana T, Fernández-Orland A, Ferrándiz-Pulido L

PMID: 30126606 [PubMed - indexed for MEDLINE]

Sirolimus and other mTOR inhibitors directly activate latent pathogenic human polyomavirus replication.

Fetched: February 17th, 2020, 5:01am GMT

Sirolimus and other mTOR inhibitors directly activate latent pathogenic human polyomavirus replication.

J Infect Dis. 2020 Feb 15;:

Authors: Alvarez Orellana J, Kwun HJ, Artusi S, Chang Y, Moore PS

Abstract
BACKGROUND: Human polyomaviruses can reactivate in transplant patients causing nephropathy, progressive multifocal leukoencephalopathy, Merkel cell carcinoma, pruritic rash or trichodysplasia spinulosa. Sirolimus and related mTOR inhibitors are transplant immunosuppressants. It is unknown if they directly reactivate polyomavirus replication from latency beyond their general effects on immunosuppression.
METHODS: In vitro expression and turnover of large T (LT) proteins from BK, JC, Merkel cell, HPyV7 and trichodysplasia spinulosa polyomaviruses after drug treatment were determined by immunoblotting, proximity ligation, replicon DNA replication and whole virus immunofluorescence assays.
RESULTS: mTOR inhibition increased LT protein expression for all 5 pathogenic polyomaviruses tested. This correlated with LT stabilization, decrease in the Skp2 E3 ligase targeting these LT proteins for degradation, as well as increase in virus replication for JCV, MCV, TSV and HPyV7. Treatment with sirolimus, but not the calcineurin inhibitor tacrolimus, at levels routinely achieved in patients, resulted in a dose-dependent increase in viral DNA replication for BKV, MCV and HPyV7.
CONCLUSIONS: mTOR inhibitors, at therapeutic levels, directly activate polyomavirus replication through a Skp2-dependent mechanism, revealing a proteostatic latency mechanism common to polyomaviruses. Modifying existing drug regimens for transplant patients with polyomavirus-associated diseases may reduce symptomatic polyomavirus replication while maintaining allograft-sparing immune suppression. immunosuppression.

PMID: 32060513 [PubMed - as supplied by publisher]

Permalink for 'Ablation of soft tissue tumours by long needle variable electrode-geometry electrochemotherapy: final report from a single-arm, single-centre phase-2 study.'

Ablation of soft tissue tumours by long needle variable electrode-geometry electrochemotherapy: final report from a single-arm, single-centre phase-2 study.

Fetched: February 13th, 2020, 5:01am GMT

Ablation of soft tissue tumours by long needle variable electrode-geometry electrochemotherapy: final report from a single-arm, single-centre phase-2 study.

Sci Rep. 2020 Feb 10;10(1):2291

Authors: Simioni A, Valpione S, Granziera E, Rossi CR, Cavallin F, Spina R, Sieni E, Aliberti C, Stramare R, Campana LG

Abstract
Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treatment of small superficial lesions. Variable electrode-geometry ECT (VEG-ECT) may overcome these limitations by using long freely-placeable electrodes. Patients with bulky or deep-seated soft-tissue malignancies not amenable to resection participated in a single-arm phase-2 study (ISRCTN.11667954) and received a single course of VEG-ECT with intravenous bleomycin (15,000 IU/m2) and concomitant electric pulses applied through an adjustable electrode array. The primary outcome was radiologic complete response rate (CRR) per RECIST; secondary endpoints included feasibility, metabolic response, toxicity (CTCAE), local progression-free survival (LPFS) and patient perception (EQ-5D). During 2009-2014, we enrolled 30 patients with trunk/limb sarcomas, melanoma, Merkel-cell carcinoma, and colorectal/lung cancer. Median tumour size was 4.7 cm. Electrode probes were placed under US/TC guidance (28 and 2 patients, respectively). Median procedure duration was 80 minutes. Tumour coverage rate was 97% (29 of 30 patients). Perioperative side-effects were negligible; one patient experienced grade-3 ulceration and infection. One-month 18F-FDG-SUV decreased by 86%; CRR was 63% (95% CI 44-79%). Local control was durable in 24 of 30 patients (two-year LPFS, 62%). Patients reported an improvement in "usual activities", "anxiety/depression", and "overall health" scores. VEG-ECT demonstrated encouraging antitumour activity in soft-tissue malignancies; a single course of treatment produced high and durable responses, with low complications.

PMID: 32042142 [PubMed - in process]

Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016.

Fetched: February 12th, 2020, 5:01am GMT

Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016.

Australas J Dermatol. 2020 Feb;61(1):e34-e38

Authors: Garbutcheon-Singh KB, Curchin DJ, McCormack CJ, Smith SD

Abstract
BACKGROUND/OBJECTIVES: Merkel cell carcinoma (MCC) is a highly invasive cutaneous malignancy. The objective of this study was to investigate the incidence and trends of MCC in Victoria, Australia, between 1986 and 2016.
METHODS: Population-based, descriptive analysis of Victorian Cancer Registry (VCR) data. The de-identified records of patients with MCC were obtained from Victoria residents diagnosed between 1986 and 2016. Trends in age-standardised incidences were examined using joinpoint analysis.
RESULTS: A total of 1095 cases were found. Incidence of MCC was 3.9 per 100 000 for men and 1.5 per 100 000 for women. The incidence of MCC in men 66-85 is increasing at an annual rate of 4.2% (2.8-5.8%, 95% CI). However, since 2002 the incidence in women in the same age group has been decreasing. Whilst there is an overall stabilisation in the incidence of MCC, incidence of MCC for males is increasing. For MCC in males 85 years old and over, the incidence of MCC was 26.8 per 100 000 between 2012 and 2016. Relative 5-year survival for patients diagnosed between 2008 and 2012 is 50%.
CONCLUSION: Merkel cell carcinoma remains an aggressive cancer, especially among older men. Differences in trends seen in local data can help target preventative and early intervention management strategies in specific groups.

PMID: 32040877 [PubMed - in process]

Lambert-Eaton myasthenic syndrome and merkel cell carcinoma.

Fetched: February 12th, 2020, 5:01am GMT

Lambert-Eaton myasthenic syndrome and merkel cell carcinoma.

Cutis. 2019 May;103(5):E19-E23

Authors: Nguyen ND, Simmons DB, Bersabe AR, Duginski TM, Sladky JH, Walton D, Will M, Renshaw JS

Abstract
Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of the neuromuscular junction that is most commonly diagnosed in association with small cell lung carcinoma (SCLC). Small cell lung carcinoma is histologically similar to the aggressive cutaneous neuroendocrine malignancy Merkel cell carcinoma (MCC). We provide a full report and longitudinal clinical follow-up of a case of LEMS occurring with MCC. We also review the literature on paraneoplastic syndromes associated with MCC and other nonpulmonary small cell carcinomas.

PMID: 31233589 [PubMed - indexed for MEDLINE]

Cystic scalp lesion.

Fetched: February 12th, 2020, 5:01am GMT

Cystic scalp lesion.

Cutis. 2019 May;103(5):261;280;281

Authors: Ashton R, Colantonio SA, Beecker J

PMID: 31233577 [PubMed - indexed for MEDLINE]

Case of fulminant type 1 diabetes induced by the anti-programmed death-ligand 1 antibody, avelumab.

Fetched: February 12th, 2020, 5:01am GMT

Case of fulminant type 1 diabetes induced by the anti-programmed death-ligand 1 antibody, avelumab.

J Diabetes Investig. 2019 Sep;10(5):1385-1387

Authors: Shibayama Y, Kameda H, Ota S, Tsuchida K, Cho KY, Nakamura A, Miyoshi H, Atsumi T

Abstract
With the expansive use of immune checkpoint inhibitors, the frequency of immune-related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti-programmed death-ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81-year-old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab-induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.

PMID: 30738003 [PubMed - indexed for MEDLINE]

Permalink for 'Eyelash hair transplantation with strip composite eyebrow graft: an enhancing technique in tarsoconjunctival flap eyelid reconstruction procedure.'

Eyelash hair transplantation with strip composite eyebrow graft: an enhancing technique in tarsoconjunctival flap eyelid reconstruction procedure.

Fetched: February 9th, 2020, 5:01am GMT

Eyelash hair transplantation with strip composite eyebrow graft: an enhancing technique in tarsoconjunctival flap eyelid reconstruction procedure.

Orbit. 2019 Oct;38(5):383-386

Authors: Nava-Castañeda Á, Tovilla-Canales JL, Solano-Leal P, Garnica-Hayashi L

Abstract
Purpose: To describe and evaluate the eyelash transplantation with strip composite eyebrow graft to improve eyelid anatomy in tarsoconjunctival flap eyelid reconstruction procedure. Methods: Twenty two patients with eyelid tumors managed by local excision and reconstruction using tarsoconjunctival flap reconstruction procedure were included. Eyelash graft was performed during flap division by harvesting a graft from the eyebrow and creating a recipient pocket in the receptor eyelid. Patients had a 1-year follow up. Eyelash orientation and follicle survival rate were recorded. Demographic variables were analyzed with descriptive statistics. For eyelash follicles survival rate assessment, we evaluated the number of follicles found in the first postoperative day with the follicles found at the end of the study using the Wilcoxon signed rank test. P < 0.05 was considered statistically significant. Results: All eyelash grafts showed a good follicle orientation and no cases of eyelashes misdirection toward the eyeball were reported. No statistical differences (p > 0.05) were found in Wilcoxon signed rank test when comparing the number of follicles present at the first postoperative day and the number of follicles present at the 12th postoperative month, meaning that the vast majority of follicles survived at the end of the study. Graft ischemia, necrosis or infection were not observed. Conclusions: Tarsoconjunctival flap is an outstanding option for eyelid reconstruction and eyelash transplantation with an eyebrow composite graft is an excellent procedure to enhance and recreate a normal eyelid.

PMID: 30482080 [PubMed - indexed for MEDLINE]

Expression of Lefty predicts Merkel cell carcinoma-specific death.

Fetched: February 7th, 2020, 5:01am GMT

Expression of Lefty predicts Merkel cell carcinoma-specific death.

J Eur Acad Dermatol Venereol. 2020 Feb 05;:

Authors: Gambichler T, Ardabili S, Dreißigacker M, Scheel CH, Brand-Saberi B, Skrygan M, Stockfleth E, Becker JC

Abstract
BACKGROUND: Lefty and Nodal are transforming growth factor β-related proteins, which, beside their role in determination of laterality during embryogenesis, have also been linked with cancer progression.
OBJECTIVES: Prompted by the observed significant left-sided laterality of Merkel cell carcinoma (MCC), we addressed whether Lefty and Nodal are expressed in MCC and correlated expression patterns with clinical parameters such as MCC laterality and patient outcome.
METHODS: Expression of Lefty and Nodal in primary MCC was assessed in 29 patients by immunohistochemistry. The histology (H-)score was calculated and correlated with clinical parameters.
RESULTS: The median (range) H-score of Lefty and Nodal was 17.6 (0 - 291) and 74.9 (0.7 - 272), respectively. There was a significant correlation between Lefty and Nodal expression (correlation coefficient of 0.60, p=0.0006). There was no significant correlation between Lefty or Nodal expression with either tumour laterality, gender, age, MCPyV status, disease stage, anatomical localization of primary tumours, or disease relapse. However, low Lefty and Nodal expression were significantly associated with MCC-specific death (p=0.010 and p=0.019, respectively). Moreover, low Lefty expression was a significant independent predictor for MCC-specific death (p=0.025) as indicated by an odds ratio of 14 (95% CI: 1.43 to 137.33).
CONCLUSIONS: Lefty and Nodal expression are frequently expressed in MCC, but not correlated with tumour laterality. Importantly, our data suggest that a low level of Lefty expression in primary MCC is a strong predictor of MCC-specific death.

PMID: 32022949 [PubMed - as supplied by publisher]

Permalink for 'Merkel Cell Carcinoma Clinically Mimicking a Traumatic Suture Scar in the Nasal Vestibule: Earlier Diagnosis for Better Prognosis.'

Merkel Cell Carcinoma Clinically Mimicking a Traumatic Suture Scar in the Nasal Vestibule: Earlier Diagnosis for Better Prognosis.

Fetched: February 6th, 2020, 5:00am GMT

Merkel Cell Carcinoma Clinically Mimicking a Traumatic Suture Scar in the Nasal Vestibule: Earlier Diagnosis for Better Prognosis.

Anticancer Res. 2020 Feb;40(2):1123-1126

Authors: Jiang P, Lai J

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive form of skin cancer that is often found in sun-exposed regions of the skin in older or immunocompromised individuals. To date there have only been four cases reported of MCC found in the nasal vestibule.
CASE REPORT: We document an unusual case of MCC in the nasal vestibule of a 66-year-old female which was clinically believed to be an inflammatory reaction to a previous suture scar. The patient also had a history of dermatitis treated with UV light. The lesion was less than 5 mm in the greatest dimension and biopsied. There was small blue cell infiltrate in the dermis and the tumor cells were positive for synaptophysin, chromogranin and cytokeratin 20. They were negative for S100 proteins, melan A, human melanoma black 45 (HMB45) and lymphocyte common antigen CD45. For Ki-67, staining was positive in 90% of the tumor cells and tumor protein 53 immunoreactivity showed a wild type staining pattern. The pathological diagnosis was MCC and the patient underwent Mohs surgery with no tumor recurrence or metastasis identified at 2.5 years of follow-up.
CONCLUSION: To the best of our knowledge, cases of MCC arising in the nasal vestibule with clinical features mimicking a suture scar have not been reported. The importance of early diagnosis and treatment of MCC to improve patient prognosis are discussed.

PMID: 32014963 [PubMed - in process]

SOX10 Dot-Like Paranuclear Positivity in Merkel Cell Carcinoma: Report of 2 Cases.

Fetched: February 6th, 2020, 5:00am GMT

SOX10 Dot-Like Paranuclear Positivity in Merkel Cell Carcinoma: Report of 2 Cases.

Am J Dermatopathol. 2019 Sep;41(9):694-695

Authors: Jackson CR, Linos K

PMID: 30045074 [PubMed - indexed for MEDLINE]

The role of infectious agents in cancer of the ocular region.

Fetched: February 2nd, 2020, 5:00am GMT

The role of infectious agents in cancer of the ocular region.

APMIS. 2020 Jan 30;:

Authors: Henriksen JR, Ramberg I, Mikkelsen LH, Heegaard S

Abstract
The purpose of the study was to investigate the association between infectious agents and the development of cancer in the ocular adnexa. A comprehensive literary study was carried out, reviewing and summarizing previous reports on the topic. A broad range of malignancies of the ocular adnexa are associated with infectious agents. A strong association and possible causal relationship between the infectious agent and the development of ocular adnexal cancer are seen in Merkel cell carcinoma (Merkel cell polyomavirus), Burkitt lymphoma (Epstein-Barr virus) and Kaposi sarcoma (human herpesvirus 8). Infection with Chlamydia psittaci has been associated with the development of extranodal marginal zone B-cell lymphoma in Italy. Human papillomavirus infection has been associated with the development of squamous cell carcinomas of the ocular adnexa, although with a highly variable reported prevalence. By exploring the role of infectious agents in the ocular adnexa and the mechanism by which they contribute to oncogenesis, the diagnostics, management and prevention of these malignancies may also improve. Antibiotic treatment and vaccines against infectious agents may be valuable in future treatment. Additionally, the presence of infectious agents within the tumours may have a prognostic or predictive value.

PMID: 32003084 [PubMed - as supplied by publisher]

Merkel cell polyomavirus detected in head and neck carcinomas from Chile.

Fetched: February 2nd, 2020, 5:00am GMT

Merkel cell polyomavirus detected in head and neck carcinomas from Chile.

Infect Agent Cancer. 2020;15:4

Authors: Muñoz JP, Blanco R, Osorio JC, Oliva C, Diaz MJ, Carrillo-Beltrán D, Aguayo R, Castillo A, Tapia JC, Calaf GM, Gaggero A, Aguayo F

Abstract
Background: The role of human polyomaviruses (HPyVs) in epithelial tumors such as head and neck carcinomas (HNSCCs) including oral and oropharyngeal carcinomas has not been established. In this study, we evaluated for the first time the presence of Merkel cell polyomavirus (MCPyV), BK human polyomavirus (BKPyV), and JC human polyomavirus (JCPyV) in HNSCCs from Chilean subjects.
Methods: One hundred and twenty HNSCCs were analyzed for the presence of MCPyV, BKPyV and JCPyV using real-time polymerase chain reaction procedures. In addition, 54 oral brushes from age- and sex-paired subjects were analyzed.
Results: Of the total of 120 HNSCCs, 15 were positive for MCPyV (12.5%). Only one case was positive for BKPyV (0.8%) and none for JCPyV (0%). In subjects without cancer, only one case (1.8%) resulted positive for MCPyV and none for JCPyV and BKPyV. MCPyV was associated with HNSCCs (p = 0.0239; OR = 7.571; 95% CI: 1.192-81.46). No association was found between age (p = 0.1996), gender (p = 0.7111) or differentiation status (p > 0.9999) and MCPyV presence in HNSCCs.
Conclusions: MCPyVs were detected in HNSCCs from Chilean patients and were not detected in oral brushes from patients without cancer. More studies are warranted for defining an etiological role and clinical/molecular consequences of these viruses in HNSCCs.

PMID: 32002023 [PubMed]

Permalink for 'Targeted literature review on use of tumor mutational burden status and programmed cell death ligand 1 expression to predict outcomes of checkpoint inhibitor treatment.'

Targeted literature review on use of tumor mutational burden status and programmed cell death ligand 1 expression to predict outcomes of checkpoint inhibitor treatment.

Fetched: February 2nd, 2020, 5:00am GMT

Targeted literature review on use of tumor mutational burden status and programmed cell death ligand 1 expression to predict outcomes of checkpoint inhibitor treatment.

Diagn Pathol. 2020 Jan 30;15(1):6

Authors: Krieger T, Pearson I, Bell J, Doherty J, Robbins P

Abstract
BACKGROUND: To achieve optimal outcomes, an individual approach is needed in the treatment and care of patients. The potential value of tumor mutational burden (TMB) status and/or programmed cell death ligand 1 (PD-L1) expression as biomarkers to predict which patients are most likely to respond to checkpoint inhibitors has been explored in many studies. The goal of this targeted literature review is to identify data available for TMB status and/or PD-L1 expression that predict response to checkpoint inhibitors and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies.
METHODS: Targeted literature searches were performed using electronic medical databases (MEDLINE, Embase, and BIOSIS) and internet searches of specified sites. Bibliographies of key systematic literature reviews and meta-analyses also were reviewed for studies of interest.
RESULTS: The review identified 27 studies of non-small cell lung cancer (NSCLC), 40 studies of melanoma, 10 studies of urothelial cancer, and 5 studies of renal cell cancer indications. Studies also were identified in other cancer types, e.g., colorectal, breast, gastric, and Merkel cell cancer and squamous-cell carcinoma of the head and neck. Twelve trials, including six in NSCLC and four in melanoma, evaluated TMB as a predictor of outcomes. A TMB of ≥10 mutations per megabase was shown to be an effective biomarker in the CheckMate 227 study. PD-L1 expression was included in the majority of identified studies and was found to predict response in in melanoma and in all types of NSCLC. Prediction of response was not a prespecified analysis in some studies; others had small sample sizes and wide confidence intervals. A clear predictive trend for PD-L1 expression was not identified in renal, breast, gastric, or Merkel cell cancer.
CONCLUSION: Based on data contained in this review, assessment of TMB status and PD-L1 expression may help enhance the prediction of response to checkpoint inhibition in some tumors, such as NSCLC and melanoma. In this rapidly growing area of research, further exploratory biomarkers are being investigated including tumor-infiltrating lymphocytes, immune profiling (e.g., effector T cells or regulatory T cells), epigenetic signatures, T-cell receptor repertoire, proteomics, microbiome, and metabolomics.

PMID: 32000815 [PubMed - in process]

Permalink for 'In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.'

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

Fetched: February 2nd, 2020, 5:00am GMT

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

J Immunother Cancer. 2018 05 30;6(1):43

Authors: Xu MJ, Wu S, Daud AI, Yu SS, Yom SS

Abstract
BACKGROUND: Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT.
CASE PRESENTATION: Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease.
CONCLUSIONS: Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.

PMID: 29848371 [PubMed - indexed for MEDLINE]

Human polyomavirus modulation of the host DNA damage response.

Fetched: February 1st, 2020, 5:00am GMT

Human polyomavirus modulation of the host DNA damage response.

Virus Genes. 2020 Jan 29;:

Authors: Tahseen D, Rady PL, Tyring SK

Abstract
The human DNA damage response (DDR) is a complex signaling network constituting many factors responsible for the preservation of genomic integrity. Human polyomaviruses (HPyVs) are able to harness the DDR machinery during their infectious cycle by expressing an array of tumor (T) antigens. These molecular interactions between human polyomavirus T antigens and the DDR create conditions that promote viral replication at the expense of host genomic stability to cause disease as well as carcinogenesis in the cases of the Merkel cell polyomavirus and BK polyomavirus. This review focuses on the six HPyVs with disease association, emphasizing strain-dependent differences in their selective manipulation of the DDR. Appreciation of the HPyV-DDR interface at a molecular scale is conducive to the development of novel therapeutic approaches.

PMID: 31997082 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma.

Fetched: February 1st, 2020, 5:00am GMT

Merkel Cell Carcinoma.

Mayo Clin Proc. 2019 12;94(12):2602-2604

Authors: Erickson LA

PMID: 31806115 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma: Is There a Distinctive Ultrasound Pattern?

Fetched: February 1st, 2020, 5:00am GMT

Merkel Cell Carcinoma: Is There a Distinctive Ultrasound Pattern?

Actas Dermosifiliogr. 2019 Jul - Aug;110(6):503-506

Authors: García-Harana C, Fernandez-Canedo I, Rodriguez-Lobalzo S, de Troya-Martín M

PMID: 30797523 [PubMed - indexed for MEDLINE]

Heart Block Caused by Cardiac Metastasis From Merkel Cell Carcinoma: A Case Report.

Fetched: January 31st, 2020, 5:00am GMT

Heart Block Caused by Cardiac Metastasis From Merkel Cell Carcinoma: A Case Report.

Mayo Clin Proc Innov Qual Outcomes. 2019 Dec;3(4):510-516

Authors: Kazemi NY, Jain C, Bois MC, Behfar A, Olivier K, Markovic SN

Abstract
Merkel cell carcinoma (MCC) is a rare, rapidly proliferating skin cancer that commonly metastasizes to regional lymph nodes. We present the case of a 73-year-old woman with a history of MCC and non-Hodgkin B-cell lymphoma who presented with second-degree heart block (Mobitz type II) caused by an interatrial mass. Temporary pacing was required before biopsy, which revealed metastatic MCC. Treatment included permanent pacing, anti-programmed cell death ligand 1 immunotherapy, and radiation to the heart resulting in notable decrease in tumor size and normalized cardiac rhythm.

PMID: 31993571 [PubMed]

Merkel cell polyomavirus and non-Merkel cell carcinomas: guilty or circumstantial evidence?

Fetched: January 30th, 2020, 5:00am GMT

Merkel cell polyomavirus and non-Merkel cell carcinomas: guilty or circumstantial evidence?

APMIS. 2020 Jan 28;:

Authors: Csoboz B, Rasheed K, Sveinbjørnsson B, Moens U

Abstract
Merkel cell polyomavirus (MCPyV) is the major causative factor of the rare but aggressive cancer, Merkel cell carcinoma (MCC). Two characteristics of MCPyV-positive MCCs are integration of the viral genome and expression of a truncated version of one of its oncogenic proteins, namely large T antigen. The strong association of MCPyV with MCC development has incited researchers to further investigate a possible role of this virus in other cancers. However, many of the examples displaying the presence of the virus in the various non-MCC cancers are not able to clearly demonstrate a direct connection between cellular transformation and the presence of the virus. The prevalence of the virus is significantly lower in non-MCC cancers compared to MCCs, with a lower level of viral load and sparse viral protein expression. Moreover, the state of the viral genome, and whether a truncated large T antigen is expressed, has rarely been investigated. Nonetheless, considering the strong oncogenic potential of MCPyV proteins in MCC, the plausible contribution of MCPyV to transformation and cancer growth in non-MCC tumors cannot be ruled out. Furthermore, the absence of MCPyV in cancers does not exclude a hit-and-run mechanism, or the oncoproteins of MCPyV may potentiate the neoplastic process mediated by co-infecting oncoviruses such as high-risk human papillomaviruses and Epstein-Barr virus. The current review is focusing on the available data describing the presence of MCPyV in non-MCC tumors, with an aim to provide a comprehensive overview of the corresponding literature and to discuss the potential contribution of MCPyV to non-MCC cancer in light of this.

PMID: 31990105 [PubMed - as supplied by publisher]

New insight in endocrine-related adverse events associated to immune checkpoint blockade.

Fetched: January 29th, 2020, 5:01am GMT

New insight in endocrine-related adverse events associated to immune checkpoint blockade.

Best Pract Res Clin Endocrinol Metab. 2019 Dec 11;:101370

Authors: Elia G, Ferrari SM, Galdiero MR, Ragusa F, Paparo SR, Ruffilli I, Varricchi G, Fallahi P, Antonelli A

Abstract
Anticancer immunotherapy, in the form of immune checkpoint inhibition, is a paradigm shift that has transformed the care of patients with different types of solid and hematologic cancers. The most notable improvements have been seen in patients with melanoma, non-small-cell lung, bladder, renal, cervical, urotherial, and colorectal cancers, Merkel cell carcinoma, and Hodgkin lymphoma. Monoclonal antibodies (mAbs) targeting immune checkpoints (i.e., anti-CTLA: ipilimumab; anti-PD-1: nivolumab, pembrolizumab; anti-PD-L1: durvalumab, atezolizumab, avelumab) unleash the immune system against tumor cells targeting mainly T cells. Treatment with immune checkpoint inhibitors (ICIs) is associated with a variety of diverse and distinct immune-related adverse events (irAEs), reflecting the mechanistic underpinning of each target (i.e., CTLA-4, and PD-1/PD-L1 network). The most frequent endocrine irAEs associated with anti-PD-1 mAb treatment are thyroid dysfunctions, whereas hypophysitis is mostly linked to anti-CTLA-4 treatment. Type 1 diabetes mellitus and adrenalitis are rare irAEs. Combination therapy (anti-CTLA-4 plus anti-PD-1/PD-L1) can be associated with an increased risk and prevalence of endocrine irAEs. In this paper we discuss the pathophysiological and clinical aspects of irAEs with specific emphasis on endocrine irAEs associated with ICIs. With a growing number of patients treated with ICIs, a tight collaboration among oncologists, endocrinologists and immunologists appears necessary when the circumstances are more challenging and for better management of severe endocrine irAEs. Further investigations are urgently needed to better understand the mechanisms by which different ICIs can induce a variety of endocrine irAEs.

PMID: 31983543 [PubMed - as supplied by publisher]

p63 Expression in Merkel Cell Carcinoma: Comparative immunohistochemistry invokes TAp63 as the dominant isoform involved.

Fetched: January 26th, 2020, 5:00am GMT

p63 Expression in Merkel Cell Carcinoma: Comparative immunohistochemistry invokes TAp63 as the dominant isoform involved.

Hum Pathol. 2020 Jan 21;:

Authors: Walsh NM, Saggini A, Pasternak S, Carter MD, Fleming K, Ly TY, Doucette S

Abstract
The literature suggests that p63 expression in Merkel cell carcinoma (MCC) is associated with a poor prognosis. p63 immunohistochemistry marks the two main isoforms of this transcriptional protein, TAp63 (tumor-suppressor-like properties) and ∆Np63 (oncogenic properties). Little information about the isoform of relevance in MCC exists. p40 immunohistochemistry specifically marks ∆Np63 and using comparative, semiquantitative expression of p63 and p40 we sought to clarify the issue. Our cohort of 53 cases [28 males and 25 females, median age 79 years, (interquartile range {IQR} 71-88)] was stratified by morphology and viral status. Immunohistochemistry (p63, p40 and CK5/6) was performed, H-scores for nuclear expression of p63 and p40 were derived (2 observers; positivity ≥ 10) and inter-observer agreement was evaluated. Clinical, pathological and outcome data were documented. The results were analyzed statistically. Mortality amounted to 57% (median follow-up 686 days, IQR 292-1599). Positivity for MCPyV was observed in 29 (55%) of cases. Expression of p63 and p40 was present in 36 (69%) and 4 (8%) of cases, respectively. Increased age (p=0.0241), negative MCPyV status (p=0.0185) and p63 positivity (p=0.0012) were significantly associated with mortality. The latter 2 variables were highly correlated (p=0.004). The interclass correlation between the two sets of H-scores was 0.95. Our findings support an association between p63 expression and reduced overall survival in MCC and show consistency in scoring this prognostic parameter. TAp63 is the dominant isoform of the protein involved. The paradoxical tumor suppressor-like activity of this isoform in p63 positive MCCs with reduced overall survival requires further study.

PMID: 31978504 [PubMed - as supplied by publisher]

Immunobiology of Merkel cell carcinoma.

Fetched: January 25th, 2020, 5:01am GMT

Immunobiology of Merkel cell carcinoma.

Curr Opin Oncol. 2020 Jan 16;:

Authors: Samimi M, Kervarrec T, Touze A

Abstract
PURPOSE OF REVIEW: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, which is associated in 80% of cases with the Merkel cell polyomavirus (MCPyV). Advanced stages respond to immune checkpoint inhibitors in 50% of cases. Major issues remain unanswered regarding its oncogenesis and optimal treatment.
RECENT FINDINGS: MCPyV-negative and MCPyV-positive MCCs have been hypothesized to derive from distinct cells, although the cell of origin remains a matter of debate. The crucial role the MCPyV small T oncoprotein was recently confirmed by its ability to inactivate p53, together with its contribution to the metastatic progression. In advanced cases, tumoral microenvironment may adequately predict responses to immunotherapies, and several mechanisms of primary and secondary resistance have been investigated.
SUMMARY: Identifying the mechanisms of oncogenesis allow experimentation of new therapeutic targets, which remain mandatory even at the era of immunotherapies. Although new insights in the mechanisms of primary and secondary resistance pave the way for development of further immunotherapy strategies, neoadjuvant strategies may challenge our whole approach of the disease.

PMID: 31972727 [PubMed - as supplied by publisher]

PD-L1 Detection-Pearls and Pitfalls Associated With Current Methodologies Focusing on Entities Relevant to Dermatopathology.

Fetched: January 22nd, 2020, 5:01am GMT

PD-L1 Detection-Pearls and Pitfalls Associated With Current Methodologies Focusing on Entities Relevant to Dermatopathology.

Am J Dermatopathol. 2019 Aug;41(8):539-565

Authors: Oh KS, Mahalingam M

Abstract
PD-L1 is a transmembrane glycoprotein with an extracellular as well as an intracellular cytoplasmic domain. Physiologically, it plays a pivotal role in regulating T-cell activation and tolerance. Many tumor cells have exploited this regulatory mechanism by overexpressing PD-L1 in an effort to escape immunologic surveillance. In this review, we parse the literature regarding the prognostic value of tumoral PD-L1 expression before discussing the various methodologies as well as the pearls and pitfalls associated with each for predicting response to anti-PD-1/PD-L1 therapies. Special attention is given to cutaneous entities in which PD-L1 expression has been documented with an emphasis on cutaneous malignancies that have seen the broadest applications of anti-PD-L1/PD-1 therapies. Currently, immunohistochemistry is the method that is most commonly used for detection of PD-L1. However, with the wide array of immunohistochemistry protocols and staining platforms available in the market, there seems to be different cutoffs not just for different entities but also for the same entity. This review is an attempt to address the need for standardization and validation of existing protocols for PD-L1 detection.

PMID: 31335407 [PubMed - indexed for MEDLINE]

Quantitative Metastatic Lymph Node Burden and Survival in Merkel Cell Carcinoma.

Fetched: January 21st, 2020, 5:00am GMT

Quantitative Metastatic Lymph Node Burden and Survival in Merkel Cell Carcinoma.

J Am Acad Dermatol. 2020 Jan 16;:

Authors: Nguyen AT, Luu M, Lu DJ, Hamid O, Mallen-St Clair J, Faries MB, Gharavi NM, Ho AS, Zumsteg ZS

Abstract
BACKGROUND: Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for number of metastatic LNs, which is a primary driver of survival in multiple cancers.
OBJECTIVE: To determine the impact of number of positive LNs on survival in MCC.
METHODS: Patients with MCC undergoing surgery were identified from the NCDB and SEER. The association between LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived using recursive partitioning analysis (RPA).
RESULTS: Among 3670 patients, increasing metastatic LN number was associated with decreased survival (P<0.001). Mortality risk increased continuously with each additional positive LN using multivariable, non-linear modeling. Using a novel staging system derived via RPA, the hazard ratio for death in multivariable regression in comparison to patients without LN involvement was 1.24 (P=0.049), 2.08 (P<0.001), 3.24 (P<0.001), and 6.13 (P<0.001) for the proposed N1a (1-3 LNs with microscopic detection), N1b (1-3 LNs with macroscopic detection), N2 (4-8 LNs), and N3 (≥9 LNs), respectively. This system was validated in the SEER cohort and demonstrated improved concordance compared to AJCC 8th edition.
LIMITATIONS: Retrospective design CONCLUSIONS: Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.

PMID: 31954753 [PubMed - as supplied by publisher]

Immunotherapy Merkel Adjuvant Trial

Posted: March 2nd, 2020, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage I; Merkel Cell Carcinoma, Stage II; Merkel Cell Carcinoma, Stage III; Neuroendocrine Tumors; Carcinoma Neuroendocrine Skin
Interventions: Drug: Avelumab; Drug: Placebo
Sponsor: Melanoma and Skin Cancer Trials Limited
Not yet recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors

Posted: February 17th, 2020, 3:00pm GMT

Conditions: Advanced Solid Tumors; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma; Cervical Cancer; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma, Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma; Cyclin-dependent Kinase 12 Mutated Tumors; Basal Cell Carcinoma (Unresectable or Metastatic); Sarcomatoid Renal Cell Carcinoma; Clear Cell Ovarian or Endometrial Carcinoma; Anal Carcinoma; Squamous Cell Penile Carcinoma; DNA Polymerase Epsilon Mutated Tumors (P286R and V411L); Hepatocellular Carcinoma
Intervention: Drug: INCB099318
Sponsor: Incyte Corporation
Not yet recruiting

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

Posted: February 10th, 2020, 3:00pm GMT

Condition: Metastatic Merkel Cell Carcinoma
Interventions: Drug: Avelumab; Radiation: External Beam Radiation Therapy (EBRT); Radiation: Lutetium-177 (177Lu)-DOTATATE
Sponsor: Melanoma and Skin Cancer Trials Limited
Not yet recruiting

A Study to Evaluate the Safety and Pharmacokinetics of OC-001 in Patients With Locally Advanced or Metastatic Cancers

Posted: February 7th, 2020, 3:00pm GMT

Conditions: Cancer; Neoplasms; Metastatic Cancer; Triple Negative Breast Cancer; Gastric Cancer; Cervical Cancer; Ovarian Cancer; Hepatocellular Carcinoma; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma; Urothelial Neoplasm; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Locally Advanced Solid Tumor; Locally Advanced Malignant Neoplasm; Squamous Cell Carcinoma; Sarcoma; Merkel Cell Carcinoma; Bladder Cancer
Interventions: Drug: OC-001; Drug: OC-001 in Combination
Sponsor: Ocellaris Pharma, Inc.
Not yet recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors

Posted: January 27th, 2020, 3:00pm GMT

Conditions: Advanced Solid Tumor; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma; Cervical Cancer; HepatoCellular Carcinoma; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma
Intervention: Drug: INCB099280
Sponsor: Incyte Corporation
Not yet recruiting

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

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

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute; University of Southern California
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

Posted: May 2nd, 2019, 2:00pm GMT

Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Sarcoma; Mesothelioma; Neuroendocrine Tumors; Squamous Cell Cancer; Merkel Cell Carcinoma; Mismatch Repair Deficiency; Microsatellite Instability
Interventions: Biological: Tumor Infiltrating Lymphocytes (TIL); Drug: Fludarabine + Cyclophosphamide combination
Sponsor: Udai Kammula
Recruiting

QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy

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

Condition: Merkel Cell Carcinoma
Interventions: Biological: Avelumab; Biological: N-803; Biological: haNK™
Sponsors: NantKwest, Inc.; NantCell, Inc.
Recruiting

Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

Posted: December 20th, 2018, 3:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: Pembrolizumab (MK-3475)
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Intratumoral AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

Posted: September 26th, 2018, 2:00pm GMT

Conditions: Advanced or Metastatic Solid Tumors; Advanced or Metastatic Melanoma; Advanced or Metastatic Head and Neck Squamous Cell Carcinoma; Advanced or Metastatic Cutaneous Squamous Cell Carcinoma; Advanced or Metastatic Merkel Cell Carcinoma
Interventions: Drug: AST-008; Biological: Pembrolizumab; Biological: Cemiplimab
Sponsor: Exicure, Inc.
Recruiting

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

Posted: June 4th, 2018, 2:00pm GMT

Conditions: Malignant Melanoma; Merkel Cell Carcinoma
Intervention: Diagnostic Test: Visionsense™ VS3 - Stereoscopic High Definition Visualisation System (VS3-3DHD)
Sponsor: University Hospital Inselspital, Berne
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

Permalink for 'Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies'

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

Posted: April 24th, 2017, 2:00pm GMT

Conditions: Advanced Malignancies; Metastatic Cancer
Interventions: Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab
Sponsor: Incyte Biosciences International Sàrl
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

Permalink for 'An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors'

An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors

Posted: July 2nd, 2015, 2:00pm GMT

Condition: Various Advanced Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Relatlimab; Drug: Daratumumab
Sponsors: Bristol-Myers Squibb; Ono Pharmaceutical Co. Ltd
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

Permalink for 'Chemotherapy For Metastatic Grade 3 Poorly Differentiated NEuroendocrine Carcinoma Of GastroEnteroPancreatic And Unknown Primary'

Chemotherapy For Metastatic Grade 3 Poorly Differentiated NEuroendocrine Carcinoma Of GastroEnteroPancreatic And Unknown Primary

Posted: March 27th, 2020, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: FOLFOXIRI Protocol; Drug: Cisplatin injection
Sponsors: Federation Francophone de Cancerologie Digestive; National Cancer Institute, France
Not yet recruiting

Mobile Application to Collect PRO Data in NET Patients

Posted: March 27th, 2020, 2:00pm GMT

Condition: Neuroendocrine Neoplasms (Tumours)
Intervention:
Sponsors: King's College Hospital NHS Trust; Ampersand Health Ltd; Neuroendocrine Cancer UK
Not yet recruiting

Gallium-68 Labeled LM3 PET/CT in Neuroendocrine Tumors

Posted: March 24th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Diagnostic Test: Gallium-68 NODAGA-LM3 PET/CT; Diagnostic Test: Gallium-68 DOTA-LM3 PET/CT; Diagnostic Test: Gallium-68 DOTATATE PET/CT
Sponsor: Peking Union Medical College Hospital
Recruiting

National Cancer Institute "Cancer Moonshot Biobank"

Posted: March 19th, 2020, 2:00pm GMT

Conditions: Acute Myeloid Leukemia; Castration-Resistant Prostate Carcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Hematopoietic and Lymphoid Cell Neoplasm; Lung Non-Small Cell Carcinoma; Lung Small Cell Carcinoma; Malignant Solid Neoplasm; 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; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Refractory Plasma Cell Myeloma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8
Interventions: Procedure: Biospecimen Collection; Other: Medical Chart Review
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Immunotherapy Merkel Adjuvant Trial

Posted: March 2nd, 2020, 3:00pm GMT

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients

Posted: March 2nd, 2020, 3:00pm GMT

Conditions: Melanoma; Hepatocellular Carcinoma; Non Small Cell Lung Cancer; Endometrial Cancer
Interventions: Biological: VV1; Biological: Cemiplimab
Sponsors: Vyriad, Inc.; Regeneron Pharmaceuticals
Not yet recruiting

Permalink for 'Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial'

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 3:00pm GMT

Conditions: Ectomesenchymoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade II Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade II Glioma; Wilms Tumor
Intervention: Drug: Tipifarnib
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Database ITANET - ENETS Registry

Posted: February 24th, 2020, 3:00pm GMT

Condition: Gastro-entero Pancreatic Neuroendocrine Tumors
Intervention:
Sponsor: Italian Association Neuroendocrine Tumors
Recruiting

Permalink for 'A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation'

A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation

Posted: February 21st, 2020, 3:00pm GMT

Conditions: Solid Tumor; Medullary Thyroid Cancer
Intervention: Drug: Selpercatinib
Sponsors: Eli Lilly and Company; Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Not yet recruiting

$Permalink for 'Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study'$

Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study

Posted: February 20th, 2020, 3:00pm GMT

Conditions: Grade I Meningioma; Grade II Meningioma; Grade III Meningioma; Intracranial Neoplasm; Nerve Sheath Neoplasm; Pituitary Gland Adenoma; Schwannoma
Interventions: Radiation: Hypofractionated Radiation Therapy; Radiation: Photon Beam Radiation Therapy; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: Emory University; National Cancer Institute (NCI)
Not yet recruiting

Permalink for 'Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET)'

Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET)

Posted: February 19th, 2020, 3:00pm GMT

Conditions: Pulmonary Neuroendocrine Neoplasm; Pheochromocytoma; Paraganglioma; Thymus Carcinoid
Intervention: Drug: 177Lu-DOTATOC
Sponsor: Excel Diagnostics and Nuclear Oncology Center
Not yet recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors

Posted: February 17th, 2020, 3:00pm GMT

Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas

Posted: February 13th, 2020, 3:00pm GMT

Conditions: Neuroendocrine Carcinoma; Digestive Cancer
Interventions: Drug: Neoadjuvant treatment; Drug: Adjuvant treatment
Sponsors: GERCOR - Multidisciplinary Oncology Cooperative Group; Fondation ARCAD
Not yet recruiting

Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

Posted: February 12th, 2020, 3:00pm GMT

Conditions: Brain Tumor; Metabolic Disturbance; Inflammatory Response; Oxygen Deficiency
Interventions: Drug: Dexmedetomidine; Other: Normal saline
Sponsor: Georgia Tsaousi
Not yet recruiting

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

Posted: February 10th, 2020, 3:00pm GMT

A Study to Evaluate the Safety and Pharmacokinetics of OC-001 in Patients With Locally Advanced or Metastatic Cancers

Posted: February 7th, 2020, 3:00pm GMT

Study Comparing Lymphoseek® vs. Albumin Nanocolloid in Head and Neck, Melanoma and Breast Cancer

Posted: February 7th, 2020, 3:00pm GMT

Conditions: Head Cancer; Neck Cancer; Melanoma; Breast Cancer
Interventions: Drug: Lymphoseek; Drug: Nanocoll
Sponsor: Anna Cruceta
Not yet recruiting

18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors

Posted: February 6th, 2020, 3:00pm GMT

Conditions: Neural Crest Tumor; Neuroendocrine Tumors
Interventions: Drug: (18F)MFBG; Device: PET/CT; Other: Venous blood samples
Sponsor: Universitaire Ziekenhuizen Leuven
Recruiting

Permalink for 'Tumor Necrosis Factor (TNF) and Glucocorticoid Antagonist for Gulf War Illness (GWI)-Associated Multi-symptom Disease Homeostasis Reset'

Tumor Necrosis Factor (TNF) and Glucocorticoid Antagonist for Gulf War Illness (GWI)-Associated Multi-symptom Disease Homeostasis Reset

Posted: February 5th, 2020, 3:00pm GMT

Condition: Gulf War Illness
Interventions: Drug: Etanercept; Drug: Mifepristone
Sponsors: Nova Southeastern University; RTI International; Rochester General Hospital
Not yet recruiting

Evaluation of Acupuncture Effects for Complications After Surgery of Cerebellopontine Angle Tumor in Skull Base

Posted: January 31st, 2020, 3:00pm GMT

Conditions: Acupuncture; Tumor, Brain; Skull Base Tumor; Cerebellopontine Angle Tumor; Complication of Treatment; Quality of Life; Neuromuscular Blockade
Intervention:
Sponsor: Taipei Veterans General Hospital, Taiwan
Recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors

Posted: January 27th, 2020, 3:00pm GMT

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HH2710 in Patient With Advanced Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Advanced Tumors; Melanoma; Non-Small-Cell Lung Cancer; Erdheim-Chester Disease; Other RAS/RAF/MEK/ERK Mutated Tumors
Intervention: Drug: HH2710
Sponsor: ShangHai HaiHe Pharmaceutical
Recruiting

Study of INBRX-106 in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Solid Tumor; Non-Small Cell Lung Cancer; Melanoma; Head and Neck Cancer; Gastric Cancer; Renal Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: INBRX-106 - Hexavalent OX40 agonist antibody; Drug: Pembrolizumab
Sponsor: Inhibrx, Inc.
Recruiting

Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer

Posted: December 11th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 177Lu-DOTATOC
Sponsors: University of Warmia and Mazury; Maria Sklodowska-Curie Institute - Oncology Center; The Medical University of Warsaw; Poland; The Diagnostic and Therapeutic Center Gammed; Poland; National Center for Research and Development, Poland
Recruiting

Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma

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

Condition: Advanced Melanoma
Intervention: Drug: Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2
Sponsors: University Hospital, Basel, Switzerland; GMP network of Basel
Not yet recruiting

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

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

A Study of ZN-c3 in Participants With Solid Tumors

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

Conditions: Solid Tumor; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Triple Negative Breast Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Malignant Melanoma; Non Small Cell Lung Cancer; Urothelial Carcinoma
Interventions: Drug: ZN-c3; Drug: Talazoparib; Drug: Pembrolizumab
Sponsors: K-Group Beta; IQVIA Biotech
Recruiting

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

Posted: September 6th, 2019, 2:00pm GMT

Conditions: Metastatic Large Cell Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Metastatic Neuroendocrine Neoplasm; Metastatic Small Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study'

Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study

Posted: August 28th, 2019, 2:00pm GMT

Conditions: Advanced Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Collecting Duct Carcinoma; Kidney Medullary Carcinoma; Metastatic Malignant Neoplasm in the Bone; Papillary Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v8; Unclassified Renal Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radium Ra 223 Dichloride
Sponsor: National Cancer Institute (NCI)
Recruiting

Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments

Posted: August 14th, 2019, 2:00pm GMT

Conditions: Stage IV Non-small Cell Lung Cancer; Stage IV Malignant Melanoma
Intervention: Other: Plasma sample collection
Sponsor: OncoHost Ltd.
Recruiting

An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors

Posted: July 31st, 2019, 2:00pm GMT

Conditions: Ganglioneuroblastoma; Ganglioneuroma; Metastatic Neuroblastoma
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Not yet recruiting

Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain

Posted: July 26th, 2019, 2:00pm GMT

Conditions: Pancreatic Cancer; Neuroendocrine Tumors; Cachexia; Cancer
Intervention: Drug: telotristat ethyl
Sponsors: Andrew Hendifar, MD; Lexicon Pharmaceuticals
Not yet recruiting

The Master Registry of Oncology Outcomes Associated With Testing and Treatment

Posted: July 22nd, 2019, 2:00pm GMT

Conditions: Adenocarcinoma; Adenocystic Carcinoma; Anal Cancer; Appendix Cancer; Brain Tumor; Glioblastoma; Astrocytoma; Bile Duct Cancer; Cholangiocarcinoma; Bladder Cancer; Bone Cancer; Synovial Sarcoma; Chondrosarcoma; Liposarcoma; Sarcoma, Kaposi; Sarcoma,Soft Tissue; Sarcoma; Osteosarcoma; CNS Cancer; Brain Stem Neoplasms; Breast Cancer; Cervical Cancer; Colorectal Cancer; Rectal Cancer; Colon Cancer; Esophageal Cancer; Esophagus Cancer; Cancer of Colon; Pancreatic Cancer; Cancer of Pancreas; Testis Cancer; Testicular Cancer; Ureter Cancer; Renal Cell Carcinoma; Kidney Cancer; Gestational Trophoblastic Tumor; Head and Neck Neoplasms; Parotid Tumor; Larynx Cancer; Tongue Cancer; Pharynx Cancer; Salivary Gland Cancer; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Multiple Myeloma; Non Hodgkin Lymphoma; Carcinoid Tumor; Lung Cancer; Neuroendocrine Tumors; Mesothelioma; Thyroid Cancer; Parathyroid Neoplasms; Adrenal Cancer; Small Bowel Cancer; Stomach Cancer; Liver Cancer; Hepatic Cancer; Melanoma; Skin Cancer; Unknown Primary Tumors; Uterine Cancer; Fallopian Tube Cancer; Ovarian Cancer; Prostate Cancer; Vaginal Cancer; Penile Cancer; Vulvar Cancer; Waldenstrom Macroglobulinemia; Cancer, Advanced; Thymus Cancer; Nasopharyngeal Carcinoma; Multiple Endocrine Neoplasia; Pheochromocytoma; Small Cell Carcinoma; Pulmonary Carcinoma
Interventions: Diagnostic Test: Testing: Genome; Diagnostic Test: Testing: Transcriptome; Diagnostic Test: Testing: Proteome; Drug: Treatment: CAR-T
Sponsor: Taproot Health
Not yet recruiting

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

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

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; High-Frequency Microsatellite Instability; Locally Advanced Urothelial Carcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Pancreatic Adenocarcinoma; Metastatic Urothelial Carcinoma; Mismatch Repair Deficiency; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; PD-L1 Positive; Progressive Disease; Recurrent Head and Neck Squamous Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Refractory Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Pancreatic Adenocarcinoma
Interventions: Biological: Pembrolizumab; Drug: Sonidegib
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting

Permalink for 'PROCLAIM: CX-072-002: Study of PD-L1 Probody Therapeutic CX-072 in Combination With Other Anticancer Therapy in Adults With Solid Tumors'

PROCLAIM: CX-072-002: Study of PD-L1 Probody Therapeutic CX-072 in Combination With Other Anticancer Therapy in Adults With Solid Tumors

Posted: June 20th, 2019, 2:00pm GMT

Conditions: Solid Tumor; Unresectable or Metastatic Melanoma
Interventions: Drug: CX-072; Drug: Ipilimumab
Sponsor: CytomX Therapeutics
Recruiting

Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Carcinoid Tumors

Posted: May 15th, 2019, 2:00pm GMT

Conditions: Advanced Carcinoid Tumor; Digestive System Neuroendocrine Neoplasm; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Neoplasm; Unresectable Carcinoid Tumor
Interventions: Drug: Everolimus; Drug: Lenvatinib
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

Posted: May 2nd, 2019, 2:00pm GMT

Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma

Posted: April 26th, 2019, 2:00pm GMT

Condition: Melanoma
Interventions: Drug: Nivolumab; Biological: NeoVax plus Montanide; Drug: Ipilimumab
Sponsors: Dana-Farber Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

Posted: April 22nd, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroblastoma; Pheochromocytoma; Paraganglioma
Interventions: Drug: 177Lu-DOTA-tyr3-OCTREOTATE; Procedure: Peptide Receptor Radiotherapy (PRRT)
Sponsors: Sue O'Dorisio; Advanced Accelerator Applications
Not yet recruiting

Permalink for 'Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma'

Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma

Posted: April 3rd, 2019, 2:00pm GMT

Conditions: Neuroendocrine Carcinoma; Large Cell Neuroendocrine Carcinoma of the Lung; High Grade Neuroendocrine Carcinoma, Any Site
Intervention: Drug: Pembrolizumab
Sponsors: Ochsner Health System; Merck Sharp & Dohme Corp.
Recruiting

Permalink for 'Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors'

Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Posted: March 6th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Metastatic Melanoma
Interventions: Drug: losartan; Drug: dextromethorphan; Drug: caffeine; Drug: omeprazole; Drug: midazolam; Drug: rosuvastatin; Drug: bupropion immediate release (IR); Drug: encorafenib; Drug: binimetinib; Drug: modafinil
Sponsors: Array BioPharma; Pierre Fabre Laboratories
Recruiting

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Posted: February 21st, 2019, 3:00pm GMT

Conditions: Melanoma; Cervical Carcinoma; Pancreatic Carcinoma; Triple Negative Breast Cancer; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors; Prostate Carcinoma; MSI-H; Mismatch Repair Deficiency; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Intrahepatic Cholangiocarcinoma
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON Clinical Research
Recruiting

Permalink for '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'

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

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

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
Recruiting

Evaluating an Amino Acid Based Medical Food w/ Diarrhea in Carcinoid Syndrome & Other NETs

Posted: October 29th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoid Tumor of GI System; Diarrhea; Carcinoid Syndrome
Intervention: Dietary Supplement: Amino Acid Based Medical Food/Drink
Sponsors: Lowell Anthony, MD; Entrinsic Health Solutions, Inc.
Recruiting

Precise DCE-MRI in Diagnosing Participants With Recurrent High Grade Glioma or Melanoma Brain Metastases

Posted: October 5th, 2018, 2:00pm GMT

Conditions: Brain Metastases; Glioma of Brain; Brain Tumor; Metastatic Melanoma
Interventions: Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Drug: Bevacizumab Injection
Sponsors: University of Southern California; National Cancer Institute (NCI)
Not yet recruiting

Intratumoral AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

Posted: September 26th, 2018, 2:00pm GMT

Permalink for 'A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System'

A Study to testABI-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

[68Ga]DOTATATE-PET/MRI in Hepatocellular Carcinoma

Posted: August 27th, 2018, 2:00pm GMT

Condition: Hepatocellular Carcinoma
Intervention: Diagnostic Test: [68Ga]DOTATATE-PET/MRI
Sponsor: University of Alabama at Birmingham
Recruiting

Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Posted: July 16th, 2018, 2:00pm GMT

Conditions: Metastatic Kidney Medullary Carcinoma; Metastatic Renal Cell Carcinoma; SMARCB1 Negative; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8
Interventions: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Drug: Ixazomib; Drug: Ixazomib Citrate
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

Posted: June 27th, 2018, 2:00pm GMT

Conditions: ATM Biallelic Inactivation; ATM Gene Mutation; ATM Monoallelic Inactivation; BRCA1 Biallelic Inactivation; BRCA1 Gene Mutation; BRCA2 Biallelic Inactivation; BRCA2 Gene Mutation; FANCA Biallelic Inactivation; Homologous Recombination Deficiency; PALB2 Biallelic Inactivation; PALB2 Gene Mutation; Prostate Adenocarcinoma Without Evidence of Neuroendocrine Differentiation; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8
Interventions: Drug: Olaparib; Procedure: Radical Prostatectomy
Sponsors: University of Washington; National Cancer Institute (NCI); AstraZeneca
Recruiting

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

Posted: June 4th, 2018, 2:00pm GMT

A Pilot Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes

Posted: May 16th, 2018, 2:00pm GMT

Condition: Metastatic Melanoma
Interventions: Drug: Tumor Infiltrating Lymphocytes; Drug: Nivolumab and Ipilimumab
Sponsor: Yale University
Recruiting

A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Posted: May 7th, 2018, 2:00pm GMT

Conditions: Melanoma; Breast Carcinoma; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Renal Cell Carcinoma; Colorectal Carcinoma; Non-small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Endometrial Carcinoma; Mesothelioma; Neuroendocrine Carcinoma; Cervical Cancer; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of the Anus; Castration-Resistant Prostate Carcinoma; Nasopharyngeal Carcinoma; Cholangiocarcinoma; Basal Cell Carcinoma; Ovarian Carcinoma; Fallopian Tube Carcinoma; Thymoma; Thymic Carcinoma; Squamous Cell Carcinoma of the Penis; Vulvar Carcinoma; Solid Tumors With Published Evidence of Anti-tumor Activity With Anti-PD1/PDL1 and/or Anti-CTLA4-directed Therapy; Malignant Adnexal Neoplasms; Non-squamous Cell Salivary Gland Carcinoma
Intervention: Biological: XmAb20717
Sponsors: Xencor, Inc.; ICON plc
Recruiting

TIL-ACT After NMA Chemo With IL-2 and Nivo Rescue in Metastatic Melanoma (mMEL)

Posted: March 23rd, 2018, 2:00pm GMT

Condition: Metastatic Melanoma
Interventions: Other: TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: Nivolumab
Sponsor: Centre Hospitalier Universitaire Vaudois
Recruiting

Ex-Vivo Expanded Allogeneic NK Cells For The Treatment Of Pediatric Solid Tumors

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

Conditions: Non-myeloablative TCR Alpha/Beta-depleted Haploidentical Hematopoietic Stem Cell Transplantation; Recurrent Lip and Oral Cavity Carcinoma; Recurrent Malignant Endocrine Neoplasm; Recurrent Malignant Female Reproductive System Neoplasm; Recurrent Malignant Male Reproductive System Neoplasm; Recurrent Malignant Mesothelioma; Recurrent Malignant Neoplasm of Multiple Primary Sites; Recurrent Malignant Oral Neoplasm; Recurrent Malignant Pharyngeal Neoplasm; Recurrent Malignant Skin Neoplasm; Recurrent Malignant Soft Tissue Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Malignant Thyroid Gland Neoplasm; Recurrent Malignant Urinary System Neoplasm; Recurrent Melanoma of the Skin; Refractory Cutaneous Melanoma; Refractory Malignant Bone Neoplasm; Refractory Malignant Endocrine Neoplasm; Refractory Malignant Female Reproductive System Neoplasm; Refractory Malignant Male Reproductive System Neoplasm; Refractory Malignant Mesothelioma; Refractory Malignant Neoplasm of Multiple Primary Sites; Refractory Malignant Oral Neoplasm; Refractory Malignant Pharyngeal Neoplasm; Refractory Malignant Skin Neoplasm; Refractory Malignant Soft Tissue Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Malignant Thyroid Gland Neoplasm; Refractory Malignant Urinary System Neoplasm
Interventions: Biological: Cord Blood-derived Expanded Allogeneic Natural Killer Cells; Drug: Cyclophosphamide; Drug: Etoposide
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

A Study of XmAb®18087 in Subjects With NET and GIST

Posted: January 26th, 2018, 3:00pm GMT

Conditions: Neuroendocrine Tumor; Gastrointestinal Neoplasm
Intervention: Biological: XmAb18087
Sponsors: Xencor, Inc.; ICON plc
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

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Posted: July 2nd, 2017, 2:00pm GMT

Conditions: Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Ga-68-DOTATATE; Drug: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)

Posted: July 2nd, 2017, 2:00pm GMT

Conditions: Mesothelioma; Uveal Melanoma; Renal Cell Carcinoma; Cholangiocarcinoma
Intervention: Drug: Niraparib
Sponsors: University of Florida; Tesaro, Inc.
Recruiting

PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer

Posted: June 7th, 2017, 2:00pm GMT

Condition: Prostate Cancer
Intervention: Drug: Avelumab
Sponsor: Andrew J. Armstrong, MD
Recruiting

Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer

Posted: May 17th, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Medullary Thyroid Cancer; Colon Cancer; Any Solid Tumor
Intervention: Drug: LOXO-292 (selpercatinib)
Sponsor: Loxo Oncology, Inc.
Recruiting

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

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

Conditions: Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma
Interventions: Other: Best Practice; Other: Laboratory Biomarker Analysis; Procedure: Supportive Care; Other: Survey Administration
Sponsor: Stanford University
Recruiting

Permalink for 'A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use'

A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use

Posted: May 9th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: [68]Ga-HA-DOTATATE
Sponsor: AHS Cancer Control Alberta
Recruiting

Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas

Posted: May 2nd, 2017, 2:00pm GMT

Condition: High Grade Malignant Neuroendocrine Carcinoma (Diagnosis)
Interventions: Drug: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel
Sponsors: University of California, San Francisco; Merck Sharp & Dohme Corp.
Recruiting

Permalink for 'Stereotactic Body Radiation Therapy With or Without Nivolumab in Treating Patients With Stage I-IIA or Recurrent Non-small Cell Lung Cancer'

Stereotactic Body Radiation Therapy With or Without Nivolumab in Treating Patients With Stage I-IIA or Recurrent Non-small Cell Lung Cancer

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

Conditions: Lung Non-Small Cell Squamous Carcinoma; Minimally Invasive Lung Adenocarcinoma; Neuroendocrine Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Lung Large Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8
Interventions: Biological: Nivolumab; Radiation: Stereotactic Body Radiation Therapy
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin

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

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm of Lung
Interventions: Drug: Durvalumab; Drug: Tremelimumab
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Recruiting

Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

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

Uveal Melanoma T Cel Therapy

Posted: March 3rd, 2017, 3:00pm GMT

Conditions: Metastatic Uveal Melanoma; Uveal Melanoma Metastatic in the Liver
Interventions: Biological: Aldesleukin; Biological: Autologous CD8+ SLC45A2-specific T Lymphocytes; Drug: Cyclophosphamide; Biological: Ipilimumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

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

Conditions: Advanced 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; Unresectable Melanoma
Interventions: Biological: Pembrolizumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Recruiting

A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma

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

Condition: Malignant Neoplasms
Interventions: Drug: RGX-104; Drug: Nivolumab; Drug: Ipilimumab; Drug: Docetaxel; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed
Sponsor: Rgenix, Inc.
Recruiting

Permalink for 'Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)'

Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)

Posted: August 22nd, 2016, 2:00pm GMT

Conditions: Uveal Melanoma; Melanoma, Uveal
Interventions: Procedure: Endoresection; Procedure: Laser diode
Sponsor: Institut Curie
Recruiting

Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

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

Condition: Desmoplastic Melanoma
Interventions: Biological: Pembrolizumab; Procedure: Therapeutic Conventional Surgery
Sponsor: National Cancer Institute (NCI)
Recruiting

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases To The Liver

Posted: March 31st, 2016, 2:00pm GMT

Conditions: Neuroendocrine Tumor, Malignant; Liver Metastases
Interventions: Device: Bland Embolization; Combination Product: Transarterial chemoembolization; Combination Product: Drug Eluting Beads Embolization
Sponsors: University of Pennsylvania; Guerbet
Recruiting

Study of Everolimus as Maintenance Therapy for Metastatic NEC With Pulmonary or Gastroenteropancreatic Origin

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

Condition: Neuroendocrine Carcinoma
Intervention: Drug: Everolimus
Sponsors: Gruppo Oncologico Italiano di Ricerca Clinica; Novartis
Recruiting

Pembrolizumab Plus Bevacizumab for Treatment of Brain Metastases in Metastatic Melanoma or Non-small Cell Lung Cancer

Posted: February 12th, 2016, 3:00pm GMT

Conditions: Melanoma; Non-small Cell Lung Cancer; Brain Metastasis
Intervention: Drug: Pembrolizumab plus Bevacizumab
Sponsor: Yale University
Recruiting

A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)

Posted: January 7th, 2015, 3:00pm GMT

Conditions: Melanoma; Lymphoma; Solid Tumor; Classical Hodgkin Lymphoma; Microsatellite-instability-high Solid Tumor
Intervention: Biological: Pembrolizumab
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Targeted Silica Nanoparticles for Real-Time Image-Guided Intraoperative Mapping of Nodal Metastases

Posted: April 8th, 2014, 2:00pm GMT

Conditions: Head and Neck Melanoma; Breast Cancer; Colorectal Cancer
Intervention: Drug: fluorescent cRGDY-PEG-Cy5.5-C dots
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting

Permalink for 'Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers'

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

Posted: December 25th, 2013, 3:00pm GMT

Conditions: Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma
Interventions: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Other: Pharmacological Study
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting

Ipilimumab and Imatinib Mesylate in Advanced Cancer

Posted: November 30th, 2012, 3:00pm GMT

Conditions: Advanced Malignant Solid Neoplasm; C-KIT Tyrosine Kinase Protein Overexpression; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Gastrointestinal Stromal Tumor; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Melanoma; Unresectable Solid Neoplasm
Interventions: Drug: Imatinib Mesylate; Biological: Ipilimumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Post-op Wellness Program for Pancreatic Cancer Patients That Uses Patient Feedback and Real-time Provider Monitoring

Posted: June 3rd, 2011, 2:00pm GMT

Conditions: Cancer Survivor; Current Smoker; Former Smoker; Malignant Head and Neck Neoplasm; Malignant Neoplasm; Metastatic Malignant Neoplasm in the Neck; Metastatic Malignant Neoplasm in the Uterine Cervix; Pancreatic Adenocarcinoma; Pancreatic Cyst; Pancreatic Neuroendocrine Carcinoma; Recurrent Colorectal Carcinoma; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Hypopharyngeal Carcinoma AJCC v7; Stage I Major Salivary Gland Cancer AJCC v7; Stage I Nasopharyngeal Carcinoma AJCC v7; Stage I Oral Cavity Cancer AJCC v6 and v7; Stage I Oropharyngeal Carcinoma AJCC v6 and v7; Stage II Colorectal Cancer AJCC v7; Stage II Hypopharyngeal Carcinoma AJCC v6 and v7; Stage II Major Salivary Gland Cancer AJCC v7; Stage II Nasopharyngeal Carcinoma AJCC v7; Stage II Oral Cavity Cancer AJCC v6 and v7; Stage II Oropharyngeal Carcinoma AJCC v6 and v7; Stage IIA Colorectal Cancer AJCC v7; Stage IIB Colorectal Cancer AJCC v7; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Hypopharyngeal Carcinoma AJCC v7; Stage III Laryngeal Cancer AJCC v6 and v7; Stage III Major Salivary Gland Cancer AJCC v7; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage III Oral Cavity Cancer AJCC v6 and v7; Stage III Oropharyngeal Carcinoma AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVA Hypopharyngeal Carcinoma AJCC v7; Stage IVA Laryngeal Cancer AJCC v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Carcinoma AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Stage IVB Hypopharyngeal Carcinoma AJCC v7; Stage IVB Laryngeal Cancer AJCC v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Carcinoma AJCC v7
Interventions: Behavioral: Exercise Intervention; Other: Health Telemonitoring; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; 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; Metastatic Lung Cancer; Metastatic Colon Cancer; Metastatic Colorectal Cancer; Metastatic Breast Cancer; Metastatic Pancreatic Cancer
Intervention: Drug: PV-10 (10% rose bengal disodium)
Sponsor: Provectus Biopharmaceuticals, Inc.
Recruiting

Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma

Posted: June 26th, 2002, 2:00pm GMT

Conditions: Melanoma; Dysplastic Nevus Syndrome
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Eligibility Screening and Tissue Procurement for the NIH Intramural Research Program Clinical Protocols

Posted: November 15th, 2001, 3:00pm GMT

Conditions: Breast Cancer; Prostate Cancer; Lung Cancer; Sarcoma; Melanoma
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Diagnosis of Pheochromocytoma

Posted: March 3rd, 2000, 3:00pm GMT

Conditions: Pheochromocytoma; Endocrine Disease; Endocrine Diseases
Interventions: Drug: ([18F]-DOPA); Drug: [68Ga]-DOTATATE; Drug: ([18F]-6F-DA)
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting

Studies of Elevated Parathyroid Activity

Posted: November 4th, 1999, 3:00pm GMT

Conditions: Hyperparathyroidism; Hypocalcemia; Parathyroid Neoplasm; Multiple Endocrine Neoplasia; MEN1
Intervention:
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruiting

Permalink for 'Nomograms predict survival outcomes for distant metastatic pancreatic neuroendocrine tumor: A population based STROBE compliant study.'

Nomograms predict survival outcomes for distant metastatic pancreatic neuroendocrine tumor: A population based STROBE compliant study.

Fetched: March 31st, 2020, 5:01am GMT

Nomograms predict survival outcomes for distant metastatic pancreatic neuroendocrine tumor: A population based STROBE compliant study.

Medicine (Baltimore). 2020 Mar;99(13):e19593

Authors: Li G, Tian ML, Bing YT, Wang HY, Yuan CH, Xiu DR

Abstract
As a rare malignant tumor, pancreatic neuroendocrine tumor (pNET) has very low incidence. However, most of the pNET patients would develop the distant metastasis, which significantly reduces patients' survival rate. Therefore, it is very important to construct a prognostic model of pNET patients with distant metastasis based on a large database to guide clinical application and treatment. The aim of this study is to establish nomograms for cancer-specific survival (CSS) and overall survival (OS) of patients with distant metastatic pNET based on the Surveillance, Epidemiology, and End Results (SEER) database.SEER were reviewed and the patients with pNET diagnosed between 1973 and 2015 were selected. After screening, a total of 624 cases were included in the study. Patients were randomly divided into a training cohort (n = 416) and a validation cohort (n = 208). Cox proportional hazard analysis revealed that age at diagnosis of ≥80 years, year of diagnosis, histological grade, and primary site surgery were independent factors both for CSS and OS. The nomograms indicated good accuracy in predicting 1-, 3-, and 5-year survival, with a C-index of 0.777 (95% confidence interval [CI], 0.743-0.811) for CSS and 0.772 (95% CI 0.738-0.806) for OS in training cohort. In the validation cohort, the C-index was 0.798 (95% CI 0.755-0.841) for CSS and 0.797 (95% CI 0.753-0.841) for OS. The calibration curves showed satisfactory consistency between predicted and actual survival.The study establishes excellent prognostic nomograms for CSS and OS for pNET patients with distant metastasis. They can be used to accurately predict survival rate, and provide useful information to physicians and patients.

PMID: 32221079 [PubMed - in process]

Permalink for '[Analysis of Collision Carcinoma of Larynx Between Moderately Differentiated Squamous Cell Carcinoma and Poorly Differentiated Neuroendocrine Carcinoma from One Case].'

[Analysis of Collision Carcinoma of Larynx Between Moderately Differentiated Squamous Cell Carcinoma and Poorly Differentiated Neuroendocrine Carcinoma from One Case].

Fetched: March 30th, 2020, 5:01am GMT

[Analysis of Collision Carcinoma of Larynx Between Moderately Differentiated Squamous Cell Carcinoma and Poorly Differentiated Neuroendocrine Carcinoma from One Case].

Sichuan Da Xue Xue Bao Yi Xue Ban. 2020 Mar;51(2):261-263

Authors: Qiao YX, Zhao Y, Jiang LL

Abstract
A 75-year-old male patient was hospitalized in hoarseness for 2 months. Laryngoscopy showed a mass protruding in right laryngeal chamber and covering the middle part of right vocal cord. Since tumor biopsy showed low differentiation cancer, he received total laryngectomy, and post-operative pathological result found composite carcinoma, which containing medium differentiated squamous cell carcinoma (about 5%) and low differentiated neuroendocrine carcinoma (about 95%). The growth status of tumor indicated it was collision carcinoma. After postoperative regular radiotherapy, no recurrence was found at 6 months of follow-up. The incidence of head and neck collision carcinoma is quite low, and the majority of them occurs in thyroid, which is rare in larynx. The confirmed diagnosis of larynx collision carcinoma is based on postoperative pathological study. The choice of treatment for collision cancer is closely related to the pathological components, the location of the disease and whether there is distant metastasis.

PMID: 32220198 [PubMed - as supplied by publisher]

Permalink for 'Gastric perforation during ligation-assisted endoscopic mucosal resection of a neuroendocrine tumor: banding without resection may be a safer option.'

Gastric perforation during ligation-assisted endoscopic mucosal resection of a neuroendocrine tumor: banding without resection may be a safer option.

Fetched: March 30th, 2020, 5:01am GMT

Gastric perforation during ligation-assisted endoscopic mucosal resection of a neuroendocrine tumor: banding without resection may be a safer option.

Endoscopy. 2020 Mar 27;:

Authors: Bas-Cutrina F, Ballester-Clau R, González-Huix F, Gornals JB

PMID: 32219785 [PubMed - as supplied by publisher]

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

Fetched: March 30th, 2020, 5:01am GMT

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

Ann Surg Oncol. 2020 Mar 26;:

Authors: Marincola Smith P, Baechle J, Tan MC, Solórzano CC, Lopez-Aguiar AG, Dillhoff M, Beal EW, Poultsides G, Cannon JGD, Rocha FG, Crown A, Cho CS, Beems M, Winslow ER, Rendell VR, Krasnick BA, Fields RC, Maithel SK, Bailey CE, Idrees K

Abstract
BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear.
PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS).
RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006].
CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

PMID: 32219725 [PubMed - as supplied by publisher]

Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors.

Fetched: March 30th, 2020, 5:01am GMT

Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors.

Cell Oncol (Dordr). 2020 Mar 26;:

Authors: Mahalakshmi B, Baskaran R, Shanmugavadivu M, Nguyen NT, Velmurugan BK

Abstract
BACKGROUND: Insulinoma-associated protein 1 (INSM1), a transcriptional regulator with a zinc-finger DNA-binding domain, has been validated as a cytoplasmic marker for neuroendocrine differentiation of tumor cells. Next to its abundant expression in the fetal pancreas, it is expressed in brain tumors, pheochromocytomas, medullary thyroid carcinomas, insulinomas and pituitary and small-cell lung carcinomas. INSM1 is not expressed in normal adult tissues and/or most non-neuroendocrine tumors. It regulates various downstream signaling pathways, including the Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1 and N-Myc pathways. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumors, its role in tumor development has remained unclear.
CONCLUSIONS: Here, we highlight INSMI expression, as well as its diagnostic significance and use as a therapeutic target in various neuroendocrine tumors. Targeting signaling pathways or gene expression alterations associated with INSM1 expression may be instrumental for the design of novel therapeutic strategies for neuroendocrine tumors.

PMID: 32219703 [PubMed - as supplied by publisher]

Probing the Protein-Protein Interaction Between the ATRXADD Domain and the Histone H3 Tail.

Fetched: March 30th, 2020, 5:01am GMT

Probing the Protein-Protein Interaction Between the ATRXADD Domain and the Histone H3 Tail.

Molecules. 2020 Mar 25;25(7):

Authors: Zaino AM, Dash RC, Hadden MK

Abstract
While loss-of-function mutations in the ATRX gene have been implicated as a driving force for a variety of pediatric brain tumors, as well as pancreatic neuroendocrine tumors, the role of ATRX in gene regulation and oncogenic development is not well-characterized. The ADD domain of ATRX (ATRXADD) localizes the protein to chromatin by specifically binding to the histone H3 tail. This domain is also a primary region that is mutated in these cancers. The overall goal of our studies was to utilize a variety of techniques (experimental and computational) to probe the H3:ATRXADD protein-protein interaction (PPI). We developed two biochemical assays that can be utilized to study the interaction. These assays were utilized to experimentally validate and expand upon our previous computational results. We demonstrated that the three anchor points in the H3 tail (A1, K4, and K9) are all essential for high affinity binding and that disruption of more than one contact region will be required to develop a small molecule that disrupts the PPI. Our approach in this study could be applied to other domains of ATRX, as well as PPIs between other distinct proteins.

PMID: 32218364 [PubMed - as supplied by publisher]

Permalink for 'Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy.'

Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy.

Fetched: March 30th, 2020, 5:01am GMT

Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy.

Cancers (Basel). 2020 Mar 25;12(4):

Authors: Signore A, Lauri C, Auletta S, Varani M, Onofrio L, Glaudemans AWJM, Panzuto F, Marchetti P

Abstract
Molecular medicine has gained clinical relevance for the detection and staging of oncological diseases, to guide therapy decision making and for therapy follow-up due to the availability of new highly sensitive hybrid imaging camera systems and the development of new tailored radiopharmaceuticals that target specific molecules. The knowledge of the expression of different receptors on the primary tumor and on metastases is important for both therapeutic and prognostic purposes and several approaches are available aiming to achieve personalized medicine in different oncological diseases. In this review, we describe the use of specific radiopharmaceuticals to image and predict therapy response in breast cancer and neuroendocrine tumors since they represent a paradigmatic example of the importance of tumoral characterization of hormonal receptors in order to plan a tailored treatment. The most attractive radiopharmaceuticals for breast cancer are 16α-[18F]-fluoro-17β-estradiol for PET assessment of the estrogen expression, radiolabeled monoclonal antibody trastuzumab to image the human epidermal growth factor receptor 2, but also the imaging of androgen receptors with [18F]-fluorodihydrotestosterone.

PMID: 32218303 [PubMed - as supplied by publisher]

Loss of copy of MIR1-2 increases CDK4 expression in ileal neuroendocrine tumors.

Fetched: March 23rd, 2020, 5:01am GMT

Loss of copy of MIR1-2 increases CDK4 expression in ileal neuroendocrine tumors.

Oncogenesis. 2020 Mar 20;9(3):37

Authors: Contractor T, Harris CR

Abstract
Ileal neuroendocrine tumors (I-NETs) are the most common tumors of the small intestine. Although I-NETs are known for a lack of recurrently mutated genes, a majority of tumors do show loss of one copy of chromosome 18. Among the genes on chromosome 18 is MIR1-2, which encodes a microRNA, MIR1-3p, with high complementarity to the mRNA of CDK4. Here we show that transfection of neuroendocrine cell lines with MIR1-3p lowered CDK4 expression and activity, and arrested growth at the G1 stage of the cell cycle. Loss of copy of MIR1-2 in ileal neuroendocrine tumors associated with increased expression of CDK4. Genetic events that attenuated RB activity, including loss of copy of MIR1-2 as well as loss of copy of CDKN1B and CDKN2A, were more frequent in tumors from patients with metastatic I-NETs. These data suggest that inhibitors of CDK4/CDK6 may benefit patients whose I-NETs show loss of copy of MIR1-2, particularly patients with metastatic disease.

PMID: 32198354 [PubMed - as supplied by publisher]

Insulinoma-associated protein 1 (INSM-1) expression in medullary thyroid carcinoma FNA: a multi-institutional study.

Fetched: March 23rd, 2020, 5:01am GMT

Insulinoma-associated protein 1 (INSM-1) expression in medullary thyroid carcinoma FNA: a multi-institutional study.

J Am Soc Cytopathol. 2020 Feb 21;:

Authors: Maleki Z, Abram M, Dell'Aquila M, Kilic I, Lu R, Musarra T, Barkan G, Rajakorpi E, Rossi ED, Kholová I

Abstract
INTRODUCTION: Insulinoma-associated protein 1 (INSM-1) is expressed in both normal tissues and neoplasms with neuroendocrine differentiation such as small cell lung carcinoma and pancreatic neuroendocrine tumors. The aim of this study was to evaluate the INSM-1 expression in medullary thyroid carcinoma (MTC) in the aspirated material and its preoperative diagnostic value.
MATERIALS AND METHODS: MTC cases with available cytological material from 5 institutions were retrospectively identified. INSM-1 expression was analyzed in 48 cell blocks prepared from fine-needle aspiration samples from histologically confirmed cases of MTC. Twenty-nine samples were aspirates from primary thyroid lesions and 19 from secondary lesions lymph node or liver lesions. INSM-1 immunostain was done using the Ventana Automatic System (Ventana Medical Systems, Tucson, AZ). The control group consisted of 20 samples from histologically confirmed cases of papillary, follicular, and anaplastic thyroid carcinomas and secondary thyroid malignancies (squamous cell carcinoma, malignant melanoma).
RESULTS: The male to female (M:F) ratio in MTC group was 1:1.5 and the average age was 55.6 years (range: 24-84 years). INSM-1 nuclear staining in at least 5% of cells was considered positive. Forty-five (93.75%) MTC samples were positive including all primary tumor aspirates. All control samples were negative.
CONCLUSIONS: INSM-1 nuclear positivity is a reliable marker of MTC neuroendocrine differentiation on cytology material from both primary tumor and metastases. INSM-1 can also discriminate MTC from other primary and secondary thyroid carcinomas when there are cytomorphologic overlaps.

PMID: 32197966 [PubMed - as supplied by publisher]

Usefulness of 18 F-FDG-PET/CT in the diagnosis and prediction of recurrence of pancreatic neuroendocrine neoplasms.

Fetched: March 22nd, 2020, 5:01am GMT

Usefulness of 18 F-FDG-PET/CT in the diagnosis and prediction of recurrence of pancreatic neuroendocrine neoplasms.

J Hepatobiliary Pancreat Sci. 2020 Mar 20;:

Authors: Sato A, Masui T, Yogo A, Uchida Y, Nakano K, Anazawa T, Nagai K, Takaori K, Nakamoto Y, Uemoto S

Abstract
BACKGROUND: Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up.
METHODS: We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months.
RESULTS: Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n=56), 18 F-FDG positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival.. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses.
CONCLUSIONS: The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors.

PMID: 32196985 [PubMed - as supplied by publisher]

Peptide Receptor Radionuclide Therapy: An Emerging Treatment for Gastrointestinal Neuroendocrine Tumors.

Fetched: March 22nd, 2020, 5:01am GMT

Peptide Receptor Radionuclide Therapy: An Emerging Treatment for Gastrointestinal Neuroendocrine Tumors.

Clin J Oncol Nurs. 2020 Apr 01;24(2):129-133

Authors: Myers A, Chitwood H

Abstract
Neuroendocrine tumors (NETs) are comprised of biologically diverse neoplasms. The presence of systemic symptoms is dependent on NET location and differentiation. New treatment modalities have become available, offering patients improved symptom management and survival. Advanced practice RNs (APRNs) provide direct care to and coordination of treatment for patients with NETs, including treatment of somatostatin receptor-positive disease with lutetium Lu 177 dotatate (Lutathera®) peptide receptor radionuclide therapy.

PMID: 32195999 [PubMed - as supplied by publisher]

Permalink for 'Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.'

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.

Fetched: March 22nd, 2020, 5:01am GMT

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.

Oncol Lett. 2020 Mar;19(3):2446-2456

Authors: Li X, Hou Y, Shi T, He Y, Ren D, Song Z, Wei S, Chen G, Chen J, Xu S

Abstract
Pulmonary carcinoid tumors, including typical and atypical carcinoids, are well-differentiated neuroendocrine tumors (NETs) that represent 1-2% of all lung cancer cases. In the present study, all cases of well-differentiated NETs diagnosed at Tianjin Medical University General Hospital (Tianjin, China) between 2006 and 2016 were reviewed, and 20 pulmonary carcinoid cases were identified. The clinical features of these cases were summarized, and the results of pathological and imaging examinations were collated. As a low-grade malignant pulmonary neoplasm, the molecular biological mechanism of pulmonary carcinoids is yet to be elucidated. To investigate the underlying molecular mechanisms behind pulmonary carcinoids and to determine an effective molecular targeted therapeutic strategy, next-generation sequencing (NGS) was performed using tissue samples from six patients to determine additional molecular biological characteristics that may help guide targeted therapy. A total of 27 somatic mutations in 21 genes were detected. Of note, mutations in the KIT proto-oncogene receptor tyrosine kinase, Erb-B2 receptor tyrosine kinase 4, MET proto-oncogene receptor tyrosine kinase and insulin-like growth factor 1 genes occurred in two out of six cases. Since treatments for advanced carcinoids are relatively ineffective, molecular profiling may contribute to the identification of novel treatments. In addition, the literature on mutations in pulmonary carcinoids was reviewed and available clinical information and features of this tumor type were summarized.

PMID: 32194744 [PubMed]

Permalink for 'Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.'

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.

Fetched: March 22nd, 2020, 5:01am GMT

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.

Oncol Lett. 2020 Mar;19(3):2223-2230

Authors: Dong Y, Li Y, Liu R, Li Y, Zhang H, Liu H, Chen J

Abstract
A common method to distinguish large cell neuroendocrine carcinoma (LCNEC) from non-neuroendocrine large cell carcinoma (non-NE LCC) is from using specific immunohistochemistry markers, such as CgA, Syn, CD56 and Napsin A, however, the results remain controversial using these markers. Secretagogin (SCGN) is a newly discovered biomarker of neuroendocrine cells. In the present study, the expression of SCGN in 33 cases of human lung large cell carcinoma (LCC), including 17 cases of LCNEC and 16 cases of non-neuroendocrine (NE) LCC and lung cancer cell lines (A549, H1650, H358, H292 and H661). The association between SCGN expression and the clinicopathological characteristics of patients, including sex, age, clinical stage and metastasis, was analyzed. The results revealed that the different lung cancer cell lines had different expression levels of SCGN, and the SCGN protein was localized in the nucleus and cytoplasm of A549 cells detected using immunofluorescence. A total of 54.5% (18/33) of specimens positively expressed the SCGN protein. Of the 17 patients with LCNEC, only 23.5% (4/17) of cases were CgA positive, 35.29% (6/17) were Syn positive, 41.2% (7/17) were CD56 positive, and 41.2% (7/17) were Napsin A positive. However, SCGN was positively detected in 94.1% (16/17) of patients with LCNEC, which was more frequent compared with that in CgA, Syn, CD56 and Napsin A. Analysis of the clinical characteristics indicated that SCGN expression was only significantly associated with pathological type in patients with lung cancer (P<0.001). Furthermore, a positive correlation was observed between SCGN expression and CgA, Syn, and CD56 expression in patients with LCNEC. SCGN was co-localized with the NE markers (CgA, Syn, and CD56) in A549 lung cancer cells and in LCNEC tissues. Thus, SCGN displayed more sensitivity and specificity in lung cancer cells with NE differentiation. A combined analysis of SCGN and other common NE markers may be a potential tool for diagnosing these tumors.

PMID: 32194720 [PubMed]

THBS2, a microRNA-744-5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors.

Fetched: March 22nd, 2020, 5:01am GMT

THBS2, a microRNA-744-5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors.

Oncol Lett. 2020 Mar;19(3):1683-1692

Authors: Jiao H, Zeng L, Zhang J, Yang S, Lou W

Abstract
The underlying molecular mechanisms of pancreatic neuroendocrine tumor (pNET) development have not yet been clearly identified. The present study revealed that thrombospondin 2 (THBS2) was downregulated in pNET tissues and cells. Forced expression of THBS2 inhibited the proliferation and migration of pNET cells in vitro. MicroRNA(miR)-744-5p was indicated to be a direct regulator of THBS2. Upregulation of miR-744-5p potentially caused THBS2 repression. Furthermore, THBS2 inhibited the production of matrix metalloproteinase (MMP) MMP9 through suppressing the transcriptional activity of CUT-like homeobox 1 (CUX1). CUX1 and MMP9 mediated the effect of THBS2 on pNET proliferation and migration, respectively. The results of the present study revealed a mechanistic role for THBS2 in pNET proliferation and migration, indicating that THBS2 was downregulated by miR-744-5p and further affected the CUX1/MMP9 cascade, which promoted the development of pNET.

PMID: 32194660 [PubMed]

Utility of GATA-3 Expression in the Analysis of Pituitary Neuroendocrine Tumour (PitNET) Transcription Factors.

Fetched: March 22nd, 2020, 5:01am GMT

Utility of GATA-3 Expression in the Analysis of Pituitary Neuroendocrine Tumour (PitNET) Transcription Factors.

Endocr Pathol. 2020 Mar 19;:

Authors: Turchini J, Sioson L, Clarkson A, Sheen A, Gill AJ

Abstract
With the introduction of the WHO 2017 classification of endocrine neoplasms, the use of the pituitary transcription factors PIT-1, Tpit and SF-1 has become the standard of care. However, immunohistochemistry for these transcription factors is not available in all institutions, and their reliability has been questioned. We read with interest the findings of Mete et al. that GATA-3 expression was detected in some pituitary neuroendocrine tumours (PitNET). We therefore sort to validate this in our large cohort of PitNETs. We searched the database of Royal North Shore Hospital for PitNETs between 1998 and 2012, constructed a tissue microarray and reclassified these entities based on their expression for PIT-1, Tpit and SF-1. We then scored the expression of GATA-3 immunohistochemistry on a scale of 0-2, where 0 was no staining, 1 was patchy or weak staining and 2 was strong and diffuse staining. 265 of 346 tumours were able to be classified into a specific tumour subtype, and 263 tumours had tissue available for GATA-3 immunohistochemistry. 89% of gonadotrophs and 93% of triple-negative tumours with expression for luteinising hormone and follicle-stimulating hormone were positive for GATA-3. In the triple-negative group, GATA-3 was positive in 1 mammosomatotroph and 80% of tumours with thyroid-stimulating hormone expression. In the triple-negative hormone-negative group, 21 of 33 tumours were positive (64%). The results demonstrate that GATA-3 is a useful marker to supplement the existing pituitary transcription factors, albeit slightly less sensitive and specific than previously reported. GATA-3 may be employed in addition to the current array of immunohistochemical transcription factors, especially in the resource poor setting. However, given its potential cross-reactivity with other entities of the Sella, positive staining should be interpreted with caution and in the morphological and clinical context.

PMID: 32193825 [PubMed - as supplied by publisher]

Neuroendocrine tumors of the lung: clinicopathological and molecular features.

Fetched: March 22nd, 2020, 5:01am GMT

Neuroendocrine tumors of the lung: clinicopathological and molecular features.

Surg Today. 2020 Mar 19;:

Authors: Iyoda A, Azuma Y, Sano A

Abstract
In 1970, neuroendocrine tumors of the lung were classified into three categories: typical carcinoid (TC), atypical carcinoid (AC), and small cell lung carcinoma (SCLC). The third edition of the World Health Organization (WHO) classification in 1999 defined large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinomas, whereas the fourth edition of the WHO classification redefined LCNEC as a neuroendocrine tumor. Currently, neuroendocrine tumors of the lung are classified into four main categories: TC, AC, LCNEC, and SCLC. Although the treatments for TC, AC, and SCLC have not changed remarkably, the treatment strategy for LCNEC is not yet established because of its reclassification from a variant of "large cell carcinoma" to a new category of "neuroendocrine tumor". In this review article, we discuss the pathological findings, biological behavior, and treatment of neuroendocrine tumors of the lung.

PMID: 32193632 [PubMed - as supplied by publisher]

Neuroendocrine and behavioral consequences of hyperglycemia in cancer.

Fetched: March 22nd, 2020, 5:01am GMT

Neuroendocrine and behavioral consequences of hyperglycemia in cancer.

Endocrinology. 2020 Mar 20;:

Authors: Vasquez JH, Borniger JC

Abstract
A hallmark of cancer is the disruption of cellular metabolism during the course of malignant growth. Major focus is now on how these cell-autonomous processes propagate to the tumor microenvironment, and more generally, to the entire host system. This chain of events can have major consequences for a patient's health and wellbeing. For example, metabolic 'waste' produced by cancer cells activates systemic inflammatory responses, which can interfere with hepatic insulin receptor signaling and glucose homeostasis. Research is just now beginning to understand how these processes occur, and how they contribute to systemic symptoms prevalent across cancers, including hyperglycemia, fatigue, pain, and sleep disruption. Indeed, it is only recently that we have begun to appreciate that the brain does not play a passive role in responding to cancer-induced changes in physiology. In this review, we provide a brief discussion of how oncogene-directed metabolic reprogramming disrupts host metabolism, with a specific emphasis on cancer-induced hyperglycemia. We further discuss how the brain senses circulating glucose concentrations and how this process goes awry as a response to distant neoplastic growth. Finally, as glucose-sensing neurons control diverse aspects of physiology and behavior, we link cancer-induced changes in energy balance to neuroendocrine and behavioral consequences for the host organism.

PMID: 32193527 [PubMed - as supplied by publisher]

Robotic distal pancreatectomy with splenectomy for pancreatic neuroendocrine tumor (with video).

Fetched: March 22nd, 2020, 5:01am GMT

Robotic distal pancreatectomy with splenectomy for pancreatic neuroendocrine tumor (with video).

J Visc Surg. 2020 Mar 16;:

Authors: Carrier G, Rouanet P, Colombo PE

PMID: 32192902 [PubMed - as supplied by publisher]

Harnessing therapeutic viruses as a delivery vehicle for RNA-based therapy.

Fetched: March 22nd, 2020, 5:01am GMT

Harnessing therapeutic viruses as a delivery vehicle for RNA-based therapy.

PLoS One. 2019;14(10):e0224072

Authors: Ylösmäki L, Polini B, Carpi S, Martins B, Smertina E, Feola S, Fusciello M, Peltonen K, Nieri P, Ylösmäki E, Cerullo V

Abstract
Messenger RNA (mRNA) and microRNA (miRNA)-based therapeutics have become attractive alternatives to DNA-based therapeutics due to recent advances in manufacture, scalability and cost. Also, RNA-based therapeutics are considered safe since there are no risk of inducing genomic changes as well as the potential adverse effects would be only temporary due to the transient nature of RNA-based therapeutics. However, efficient in vivo delivery of RNA-based therapeutics remains a challenge. We have developed a delivery platform for RNA-based therapeutics by exploiting the physicochemical properties of enveloped viruses. By physically attaching cationic liposome/RNA complexes onto the viral envelope of vaccinia virus, we were able to deliver mRNA, self-replicating RNA as well as miRNA inside target cells. Also, we showed that this platform, called viRNA platform, can efficiently deliver functional miRNA mimics into B16.OVA tumour in vivo.

PMID: 31644552 [PubMed - indexed for MEDLINE]

Leveraging transcriptional dynamics to improve BRAF inhibitor responses in melanoma.

Fetched: March 22nd, 2020, 5:01am GMT

Leveraging transcriptional dynamics to improve BRAF inhibitor responses in melanoma.

EBioMedicine. 2019 Oct;48:178-190

Authors: Smalley I, Kim E, Li J, Spence P, Wyatt CJ, Eroglu Z, Sondak VK, Messina JL, Babacan NA, Maria-Engler SS, De Armas L, Williams SL, Gatenby RA, Chen YA, Anderson ARA, Smalley KSM

Abstract
BACKGROUND: Melanoma is a heterogeneous tumour, but the impact of this heterogeneity upon therapeutic response is not well understood.
METHODS: Single cell mRNA analysis was used to define the transcriptional heterogeneity of melanoma and its dynamic response to BRAF inhibitor therapy and treatment holidays. Discrete transcriptional states were defined in cell lines and melanoma patient specimens that predicted initial sensitivity to BRAF inhibition and the potential for effective re-challenge following resistance. A mathematical model was developed to maintain competition between the drug-sensitive and resistant states, which was validated in vivo.
FINDINGS: Our analyses showed melanoma cell lines and patient specimens to be composed of >3 transcriptionally distinct states. The cell state composition was dynamically regulated in response to BRAF inhibitor therapy and drug holidays. Transcriptional state composition predicted for therapy response. The differences in fitness between the different transcriptional states were leveraged to develop a mathematical model that optimized therapy schedules to retain the drug sensitive population. In vivo validation demonstrated that the personalized adaptive dosing schedules outperformed continuous or fixed intermittent BRAF inhibitor schedules.
INTERPRETATION: Our study provides the first evidence that transcriptional heterogeneity at the single cell level predicts for initial BRAF inhibitor sensitivity. We further demonstrate that manipulating transcriptional heterogeneity through personalized adaptive therapy schedules can delay the time to resistance.
FUNDING: This work was funded by the National Institutes of Health. The funder played no role in assembly of the manuscript.

PMID: 31594749 [PubMed - indexed for MEDLINE]

Role of CXCR3 signaling in response to anti-PD-1 therapy.

Fetched: March 22nd, 2020, 5:01am GMT

Role of CXCR3 signaling in response to anti-PD-1 therapy.

EBioMedicine. 2019 Oct;48:169-177

Authors: Han X, Wang Y, Sun J, Tan T, Cai X, Lin P, Tan Y, Zheng B, Wang B, Wang J, Xu L, Yu Z, Xu Q, Wu X, Gu Y

Abstract
BACKGROUND: Tumor mutations and tumor microenvironment are associated with resistance to cancer immunotherapies. However, peripheral T cell in effective anti-programmed death 1 (PD-1) antibody treatment is poorly understood.
METHODS: Mass spectrometry and conventional flow cytometry were used to investigate peripheral blood cells isolated from patients. Furthermore, melanoma mouse model was performed to assess the role of CXCR3 signaling in anti-PD-1 antibody treatment.
FINDINGS: We revealed a marked increase in the percentage of CXCR3+ T cells in the blood of cancer patients after the first pembrolizumab infusion. This percentage decreased after the second infusion in responsive patients, whereas a sustained high percentage of CXCR3+ T cells was observed in patients with progressive disease. A low percentage of CXCR3+ T cells presented in patients with stable disease or a partial response was confirmed by conventional flow cytometry. Intriguingly, blockade of CXCR3 signaling exacerbated tumor growth in mice. Intratumoral injection with recombinant CXCL9/10 plus intraperitoneal injection of anti-PD1 antibody inhibited the tumor growth in mice.
INTERPRETATION: The dynamic changes in CXCR3+ T cells in blood may be a prognostic factor in anti-PD-1 immunotherapy, and promotion of CXCR3-mediated signaling may be beneficial to the anti-PD-1 therapy. FUND: This work was supported by the National Natural Science Foundation of China (Nos. 81722047, 81871944, 81670553, 81874317, 81572389, 81730100) and Jiangsu province key medical talents (Nos. ZDRCA2016026), The "Deng Feng" Distinguished Scholars Program, National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China (Number: 2018ZX09201002), and the Fundamental Research Funds for the Central Universities (020814380117).

PMID: 31521609 [PubMed - indexed for MEDLINE]

Investigating Macrophages Plasticity Following Tumour-Immune Interactions During Oncolytic Therapies.

Fetched: March 22nd, 2020, 5:01am GMT

Investigating Macrophages Plasticity Following Tumour-Immune Interactions During Oncolytic Therapies.

Acta Biotheor. 2019 Dec;67(4):321-359

Authors: Eftimie R, Eftimie G

Abstract
Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses, both innate (e.g., macrophages, which accumulate in high numbers inside solid tumours) and adaptive (e.g., [Formula: see text] T cells). In this article, we consider a mathematical approach to investigate the possible outcomes of the complex interactions between two extreme types of macrophages (M1 and M2 cells), effector [Formula: see text] T cells and an oncolytic Vesicular Stomatitis Virus (VSV), on the growth/elimination of B16F10 melanoma. We discuss, in terms of VSV, [Formula: see text] and macrophages levels, two different types of immune responses which could ensure tumour control and eventual elimination. We show that both innate and adaptive anti-tumour immune responses, as well as the oncolytic virus, could be very important in delaying tumour relapse and eventually eliminating the tumour. Overall this study supports the use mathematical modelling to increase our understanding of the complex immune interaction following oncolytic virotherapies. However, the complexity of the model combined with a lack of sufficient data for model parametrisation has an impact on the possibility of making quantitative predictions.

PMID: 31410657 [PubMed - indexed for MEDLINE]

Permalink for 'Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators.'

Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators.

Fetched: March 22nd, 2020, 5:01am GMT

Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators.

Nat Nanotechnol. 2019 09;14(9):891-901

Authors: Conniot J, Scomparin A, Peres C, Yeini E, Pozzi S, Matos AI, Kleiner R, Moura LIF, Zupančič E, Viana AS, Doron H, Gois PMP, Erez N, Jung S, Satchi-Fainaro R, Florindo HF

Abstract
A low response rate, acquired resistance and severe side effects have limited the clinical outcomes of immune checkpoint therapy. Here, we show that combining cancer nanovaccines with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for effector T-cell stimulation, expansion and survival can potentiate the efficacy of melanoma therapy. Prophylactic and therapeutic combination regimens of dendritic cell-targeted mannosylated nanovaccines with αPD-1/αOX40 demonstrate a synergism that stimulates T-cell infiltration into tumours at early treatment stages. However, this treatment at the therapeutic regimen does not result in an enhanced inhibition of tumour growth compared to αPD-1/αOX40 alone and is accompanied by an increased infiltration of myeloid-derived suppressor cells in tumours. Combining the double therapy with ibrutinib, a myeloid-derived suppressor cell inhibitor, leads to a remarkable tumour remission and prolonged survival in melanoma-bearing mice. The synergy between the mannosylated nanovaccines, ibrutinib and αPD-1/αOX40 provides essential insights to devise alternative regimens to improve the efficacy of immune checkpoint modulators in solid tumours by regulating the endogenous immune response.

PMID: 31384037 [PubMed - indexed for MEDLINE]

Poliosis Circumscripta: A Mark of Melanoma.

Fetched: March 22nd, 2020, 5:01am GMT

Poliosis Circumscripta: A Mark of Melanoma.

Am J Med. 2019 12;132(12):1417-1418

Authors: Schollenberger MD, Stein JE, Taube JM, Lipson EJ

PMID: 31242438 [PubMed - indexed for MEDLINE]

Combination of multimodal imaging features predictive of choroidal nevus transformation into melanoma.

Fetched: March 22nd, 2020, 5:01am GMT

Combination of multimodal imaging features predictive of choroidal nevus transformation into melanoma.

Br J Ophthalmol. 2019 10;103(10):1441-1447

Authors: Dalvin LA, Shields CL, Ancona-Lezama DA, Yu MD, Di Nicola M, Williams BK, Lucio-Alvarez JA, Ang SM, Maloney SM, Welch RJ, Shields JA

Abstract
AIM: To characterise combinations of multimodal imaging risk factors and predictive value for choroidal nevus transformation into melanoma.
METHODS: This is a retrospective review of multimodal imaging features for 3806 choroidal nevi from 1 January 2007 through 1 January 2017. Kaplan-Meier estimates and Cox regression analyses were used to calculate 5-year percentages of growth to melanoma and HR.
RESULTS: Using multimodal imaging, six risk factors predictive of choroidal nevus transformation into melanoma were identified, namely tumour thickness >2 mm, subretinal fluid, symptoms of visual acuity loss to 20/50 or worse, orange pigment, hollow acoustic density and tumour largest basal diameter >5 mm. Kaplan-Meier 5-year estimated tumour growth was found in 1% of nevi with no risk factors, 11% (range 9%-37%) with one factor, 22% (12%-68%) with two factors, 34% (21%-100%) with three factors, 51% (0%-100%) with four factors and 55% (0%-100%) with five factors. HR for growth was 0.1 with no factor, 2.1-7.8 with one factor, 1.8-12.1 with two factors, 4.0-24.4 with three factors, 4.6-170.0 with four factors and 12.0-595.0 with five factors. The highest HR with each combination of two, three, four or five risk factors always included symptoms of visual acuity loss and orange pigment.
CONCLUSION: Six risk factors for choroidal nevus transformation into melanoma by multimodal imaging have been identified. Risk for transformation into melanoma is 1% when no factors are present, and approaches 100% with specific combinations of three or more risk factors. Understanding how combinations of factors influence risk of transformation into melanoma can guide counselling and treatment decisions.

PMID: 30523045 [PubMed - indexed for MEDLINE]

Hepatic abnormalities identified by staging MRI and accuracy of MRI of patients with uveal melanoma.

Fetched: March 22nd, 2020, 5:01am GMT

Hepatic abnormalities identified by staging MRI and accuracy of MRI of patients with uveal melanoma.

Br J Ophthalmol. 2019 09;103(9):1266-1271

Authors: Francis JH, Catalanotti F, Landa J, Barker CA, Shoushtari AN, Abramson DH

Abstract
BACKGROUND: Metastases to the liver are often the first finding in patients with uveal melanoma with extraocular disease, but little has been published on the utility of staging MRI at initial diagnosis. We aimed to evaluate the proportion of abnormal hepatic findings on baseline MRI and accuracy of MRI in patients with newly diagnosed uveal melanoma.
METHODS: This is a single-centre, retrospective, institutional review board-approved study of 145 consecutive patients diagnosed with uveal melanoma, at Memorial Sloan Kettering Cancer Center between 2004 and 2016, who had staging MRI within 1 month of diagnosis. Scans were classified as normal or abnormal, and further distinguished as abnormal non-metastatic, uncharacterisable lesions and suspicious for metastasis. Where available, follow-up MRI (at ~1 year) or biopsies were reviewed.
RESULTS: MRI in 145 patients revealed 62% (90) with abnormal hepatic findings; out of these 87% (78) had non-metastatic benign findings, 6.7% (6) had unclassifiable lesions and 6.7% (6) were suspicious for metastasis (6). Abnormal non-metastatic findings included 72 focal (36 solitary and 36 multiple) and 12 diffuse lesions. Lesions suspicious for metastases were found in 6 of 145 patients (4%), despite normal liver function tests. Of these, five had confirmed liver metastases and one patient had a stable, presumed non-metastatic lesion on follow-up. In this study, the sensitivity and specificity of staging MRI for all findings were 83.3% (95% CI 35.9 to 99.6) and 99.0% (95% CI 94.3 to 99.9), respectively.
CONCLUSION: Staging MRI of patients with newly diagnosed uveal melanoma accurately identified early metastases. Furthermore, imaging revealed hepatic abnormalities in the majority of patients, although as expected few of these represented metastatic disease.

PMID: 30381389 [PubMed - indexed for MEDLINE]

Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [18F]AmBF3-TATE.

Fetched: March 21st, 2020, 5:01am GMT

Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [18F]AmBF3-TATE.

EJNMMI Res. 2020 Mar 19;10(1):25

Authors: Lau J, Pan J, Rousseau E, Uribe CF, Seelam SR, Sutherland BW, Perrin DM, Lin KS, Bénard F

Abstract
INTRODUCTION: [18F]AmBF3-TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [18F]AmBF3-TATE were assessed with good laboratory practice (GLP) standards.
METHODS: ICR mice were intravenously administered 0.8-2.0 MBq of [18F]AmBF3-TATE, with one group pre-injected with 100 μg of [19F]AmBF3-TATE 30 min before radiopharmaceutical administration to assess uptake specificity. The mice were euthanized at 0.5, 1, 2, or 4 h post-injection (p.i.). Blood and tissues were collected, weighed, and counted on a gamma counter to determine percentage injected dose per gram (%ID/g). Dosimetry was calculated based on biodistribution data using the mouse and human phantoms included in OLINDA. Acute toxicity was assessed in Sprague-Dawley rats at the dose of 0.742 mg/kg [19F]AmBF3-TATE, with a 14-day observation/recovery period. Blood chemistry parameters, gross, and histopathology were evaluated. Body weight change and food consumption were monitored. The production of [18F]AmBF3-TATE was automated on a Trasis AllinOne synthesis module.
RESULTS: [18F]AmBF3-TATE was cleared through the renal and hepatobiliary pathway. At 1 h p.i., the pancreas (F, 15.7 ± 3.72 and M 14.3 ± 1.61 %ID/g), stomach (F, 15.3 ± 3.63 and M, 19.0 ± 3.49 %ID/g), and lungs (F, 9.26 ± 2.24 and M, 6.17 ± 6.04 %ID/g) were the organs with the highest specific uptake. Pre-injection with [19F]AmBF3-TATE significantly reduced pancreatic uptake (F, 0.13 ± 0.03 and M, 0.18 ± 0.09 %ID/g) at 1 h p.i. For dosimetry extrapolated to the average adult human, the bladder (0.027-0.030 mGy/MBq), pancreas (0.018-0.028 mGy/MBq), and lungs (0.006-0.013 mGy/MBq) are expected to receive the highest doses. No test-item related effects were observed upon evaluation of clinical observations, body weights, food consumption, clinical pathology, gross pathology, and histopathology for acute toxicity. [18F]AmBF3-TATE was produced at activity yields of 15.6 ± 4.59 GBq, average molar activity of 435 ± 162 GBq/μmol, and radiochemical purity of 98.0 ± 1.73% with the automated synthesizer.
CONCLUSION: [18F]AmBF3-TATE binds specifically to SSTR2. At 1000× clinical dose, [19F]AmBF3-TATE was well tolerated with no treatment-related adverse effects.

PMID: 32189151 [PubMed]

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

Fetched: March 21st, 2020, 5:01am GMT

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

Genome Med. 2020 Mar 18;12(1):30

PMID: 32188490 [PubMed - in process]

Permalink for 'Progressive Disease in Sentinel-negative Melanoma Patients: Biological Differences and Importance of Sentinel Lymph Node Biopsy.'

Progressive Disease in Sentinel-negative Melanoma Patients: Biological Differences and Importance of Sentinel Lymph Node Biopsy.

Fetched: March 21st, 2020, 5:01am GMT

Progressive Disease in Sentinel-negative Melanoma Patients: Biological Differences and Importance of Sentinel Lymph Node Biopsy.

Anticancer Res. 2020 Feb;40(2):891-899

Authors: Conrad A, Reinehr M, Holzmann D, Mangana J, Wanner M, Huellner M, Barnhill RL, Lugassy C, Lindenblatt N, Mihic-Probst D

Abstract
BACKGROUND/AIM: Among the most important prognostic factors in melanoma is the sentinel lymph node (SLN) status.
MATERIALS AND METHODS: Using our electronic database we identified 109 of 890 SLN-negative patients with progressive disease (PD). These patients were characterized for melanoma type, molecular type, sequence and extent of metastatic spread.
RESULTS: A total of 61 of 109 SLN-negative patients had PD in the SLN-basin indicating false-negative SLN (group-1). Forty eight of 109 patients had PD at distant sites and were therefore impossible to be identified using SLN biopsy (group-2). Despite distant spread these patients had significantly more single organ metastasis (p<0.001) and significantly longer disease-free-survival (p=0.001) compared to group-1. Additionally, to significant differences on a molecular basis between the two groups (p=0.01), all lentigo maligna and spindle-cell-melanomas belonged to group-2 and all, except one lentigo maligna melanoma, had single visceral metastasis.
CONCLUSION: Two different biological groups among SLN-negative patients with PD were demonstrated. Extravascular-migratory-metastasis, rather than hematogenous spread, might be responsible for the observed PD with single organ involvement.

PMID: 32014933 [PubMed - indexed for MEDLINE]

Gastric 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Upper Gastrointestinal Tract Melanoma.

Fetched: March 21st, 2020, 5:01am GMT

Gastric 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Upper Gastrointestinal Tract Melanoma.

Clin Nucl Med. 2020 Feb;45(2):164-167

Authors: Zhou Y, Fan QP, Tian R, Su MG

Abstract
Unexpected extraosseous uptake is common on Tc-methylene diphosphonate bone scintigraphy, but accumulation by primary upper gastrointestinal tract malignant melanoma is rarely reported. The present case is a 58-year-old woman with a 10-day history of diffuse bone pain and weakness. Her bone scintigraphy showed unexpected diffuse gastric tracer uptake. Subsequent gastroscopy revealed a number of hyperpigmented lesions in the stomach and duodenal bulb. Malignant melanoma was confirmed by histopathology and immunohistochemistry. Because extensive physical examination failed to identify any other site of ocular and cutaneous melanoma, a diagnosis of primary upper gastrointestinal tract malignant melanoma was established.

PMID: 31833932 [PubMed - indexed for MEDLINE]

Permalink for 'Re: Metastatic pheochromocytoma to the pancreas diagnosed by endoscopic ultrasound-guided fine needle aspiration: A case report and review of literature.'

Re: Metastatic pheochromocytoma to the pancreas diagnosed by endoscopic ultrasound-guided fine needle aspiration: A case report and review of literature.

Fetched: March 21st, 2020, 5:01am GMT

Re: Metastatic pheochromocytoma to the pancreas diagnosed by endoscopic ultrasound-guided fine needle aspiration: A case report and review of literature.

Diagn Cytopathol. 2020 04;48(4):414

Authors: Li M, Liu L

PMID: 31808998 [PubMed - indexed for MEDLINE]

Acute kidney injury from immune checkpoint inhibitor use.

Fetched: March 21st, 2020, 5:01am GMT

Acute kidney injury from immune checkpoint inhibitor use.

BMJ Case Rep. 2019 Oct 25;12(10):

Authors: Gordon L, Dokouhaki P, Hagel K, Prasad B

Abstract
Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

PMID: 31653633 [PubMed - indexed for MEDLINE]

Impact of the microbiome on checkpoint inhibitor treatment in patients with non-small cell lung cancer and melanoma.

Fetched: March 21st, 2020, 5:01am GMT

Impact of the microbiome on checkpoint inhibitor treatment in patients with non-small cell lung cancer and melanoma.

EBioMedicine. 2019 Oct;48:642-647

Authors: Shaikh FY, Gills JJ, Sears CL

Abstract
The microbiome is increasingly recognized for its role in multiple aspects of cancer development and treatment, specifically in response to checkpoint inhibitors. While checkpoint inhibitors have revolutionized cancer treatment by producing durable anti-tumor responses, only a minority of patients respond to the available immunotherapy drugs and accurate, sensitive and specific microbiome predictors of response to treatment remain elusive. Additionally, the specific mechanisms linking the microbiome and host immunological responses remain unclear. In this review, we examine the evidence for the gut microbiome's association with anti-tumor responses to checkpoint inhibitors in the treatment of melanoma, non-small cell lung cancer, and renal cell carcinoma. Furthermore, we discuss the current evidence available from murine models seeking to explain the immunological mechanisms that may drive this process. While this work is promising in defining the impact of gut microbiota in cancer treatment, many unanswered questions indicate the need for additional human and experimental studies.

PMID: 31597596 [PubMed - indexed for MEDLINE]

A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain.

Fetched: March 21st, 2020, 5:01am GMT

A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain.

Clin Transl Oncol. 2019 Dec;21(12):1754-1762

Authors: Márquez-Rodas I, Arance A, Berrocal A, Larios CL, Curto-García J, Campos-Tapias IX, Blanca AB, Martin-Algarra S

Abstract
PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM).
METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona).
RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3).
CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.

PMID: 31435877 [PubMed - indexed for MEDLINE]

Gastric schwannoma misdiagnosed as a GIST.

Fetched: March 21st, 2020, 5:01am GMT

Gastric schwannoma misdiagnosed as a GIST.

Acta Chir Belg. 2019 Dec;119(6):411-413

Authors: Peltrini R, Greco PA, Nasto RA, D'Alessandro A, Iacobelli A, Insabato L, Bucci L

PMID: 31311458 [PubMed - indexed for MEDLINE]

Studying the ShcD and ERK interaction under acute oxidative stress conditions in melanoma cells.

Fetched: March 21st, 2020, 5:01am GMT

Studying the ShcD and ERK interaction under acute oxidative stress conditions in melanoma cells.

Int J Biochem Cell Biol. 2019 07;112:123-133

Authors: Ahmed SBM, Amer S, Emad M, Rahmani M, Prigent SA

Abstract
The newly identified melanoma-associated adaptor ShcD was found to translocate to the nucleus upon hydrogen peroxide treatment. Therefore, the aim of this study was to identify the ShcD network in melanoma cells under oxidative stress. LC-MS/MS and GFP-trap were performed to study the ShcD phosphorylation status during acute severe oxidative stress. ShcD was found to be phosphorylated at threonine-159 (Thr159) in response to 5 mM H2O2 treatment. The GPS 2.1 phosphorylation prediction program predicted that the Thr159Pro motif, housed in the N-terminus of the ShcD-CH2 domain, is a potential phosphorylation site for MAPKs (ERK, JNK or p38). Co-immunoprecipitation experiments revealed that ShcD mainly interacts with ERK in B16 and MM138 melanoma cells under both hydrogen peroxide-untreated and -treated conditions. Moreover, ShcD interacts with both phosphorylated and un-phosphorylated ERK, although the interaction between ShcD and phospho-ERK was primarily observed after H2O2 treatment. A MEK inhibitor (U0126) enhanced the interaction between ShcD and unphosphorylated ERK under oxidative stress conditions. Furthermore, Thr159 was mutated to either alanine (A) or glutamic acid (E) to study whether the threonine phosphorylation state influences the ShcD/ERK interaction. Introducing the T159E mutation obliterated the ShcD/ERK interaction. To identify the functional impact of the ShcD/ERK interaction on cell survival signalling under oxidative stress conditions, caspase 3/7 assays and 7AAD cell death assays were used. The ShcD/ERK interaction promoted anti-survival signalling upon exposure to hydrogen peroxide, while U0126 treatment reduced death signalling. Our data also showed that the death signalling initiated by the ShcD/ERK interaction was accompanied by p21 phosphorylation. In summary, these data identified ShcD, via its interaction with ERK, as a proapoptotic protein under oxidative stress conditions.

PMID: 31121283 [PubMed - indexed for MEDLINE]

The use of in vivo reflectance confocal microscopy for the diagnosis of melanoma.

Fetched: March 21st, 2020, 5:01am GMT

The use of in vivo reflectance confocal microscopy for the diagnosis of melanoma.

Expert Rev Anticancer Ther. 2019 05;19(5):413-421

Authors: Agozzino M, Moscarella E, Babino G, Caccavale S, Piccolo V, Argenziano G

Abstract
INTRODUCTION: The use of reflectance confocal microscopy (RCM) for imaging the skin non-invasively raised constantly during the last decade. One of the main field of application is skin cancer diagnosis, and in particular melanoma diagnosis. Several studies have investigated the diagnostic accuracy of RCM as compared to dermoscopic examination, and its value in enhancing early diagnosis of dermoscopic difficult melanomas. Areas covered: The purpose of this paper was to review the principles behind RCM image acquisition as well as to describe and discuss key RCM features of melanoma. Moreover, we conducted a literature search in order to highlight the current available evidence about RCM sensitivity and specificity in the diagnosis of melanoma. Expert commentary: During the last decade, we assisted at the increasing interest in non invasive imaging tools for the diagnosis of skin cancer. RCM is one of the most studied of a series of diagnostic methods that are emerging in the field of melanoma imaging. Most probably in the future, RCM will be more frequently available in tertiary referral centres, thus the knowledge of the pros and contra of the tool and its clinical applicability is of upmost importance in order to allow correct referrals with the final aim of improving diagnostic accuracy.

PMID: 30869538 [PubMed - indexed for MEDLINE]

Demyelinating disease of the central nervous system associated with Pembrolizumab treatment for metastatic melanoma.

Fetched: March 21st, 2020, 5:01am GMT

Demyelinating disease of the central nervous system associated with Pembrolizumab treatment for metastatic melanoma.

Mult Scler. 2019 06;25(7):1005-1008

Authors: Durães J, Coutinho I, Mariano A, Geraldo A, Macário MC

Abstract
Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.

PMID: 30311534 [PubMed - indexed for MEDLINE]

Cutaneous pH landscape as a facilitator of melanoma initiation and progression.

Fetched: March 21st, 2020, 5:01am GMT

Cutaneous pH landscape as a facilitator of melanoma initiation and progression.

Acta Physiol (Oxf). 2019 01;225(1):e13105

Authors: Koch A, Schwab A

Abstract
Melanoma incidence is on the rise and currently causes the majority of skin cancer-related deaths. Yet, therapies for metastatic melanoma are still insufficient so that new concepts are essential. Malignant transformation of melanocytes and melanoma progression are intimately linked to the cutaneous pH landscape and its dysregulation in tumour lesions. The pH landscape of normal skin is characterized by a large pH gradient of up to 3 pH units between surface and dermis. The Na+ /H+ exchanger NHE1 is one of the major contributors of acidity in superficial skin layers. It is also activated by the most frequent mutation in melanoma, BRAFV 600E , thereby causing pH dysregulation during melanoma initiation. Melanoma progression is supported by an extracellular acidification and/or NHE1 activity which promote the escape of single melanoma cells from the primary tumour, migration and metastatic spreading. We propose that viewing melanoma against the background of the acid-base physiology of the skin provides a better understanding of the pathophysiology of this disease and allows the development of novel therapeutic concepts.

PMID: 29802798 [PubMed - indexed for MEDLINE]

[Perioperative management of paragangliomas and pheochromocytomas].

Fetched: March 21st, 2020, 5:01am GMT

[Perioperative management of paragangliomas and pheochromocytomas].

Medwave. 2020 Mar 04;20(2):e7830

Authors: Fermandois M, Altamirano J, Rojas F, Román C, Pinto I

Abstract
Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, characterized by a high morbidity rate due to catecholamine excess. These high levels are independent of physiologic stressors. For the diagnosis, a biochemical workup is paramount. The most widely used are plasma-free metanephrines and urinary fractionated metanephrines. Imaging studies should be initiated once the biochemical diagnosis is established. Evaluation of the patient with pheochromocytomas and paragangliomas must be done taking into account the leading causes of perioperative morbidity and mortality. The two primary interventions that have reduced perioperative mortality are alpha-adrenergic blockade and intravascular volume normalization. Another significant advance has been the establishment of laparoscopic surgery as the gold standard for the surgical approach. No anesthetic technique has been found to be superior to another. Intraoperative hemodynamic instability has been correlated with poorer outcomes; thus one of the main intraoperative goals is maintaining hemodynamic stability. Lower morbidity and almost zero mortality rates due to preoperative and intraoperative management improvements have led to a focus on the immediate and long-term postoperative care. Anual lifelong follow-up is recommended to detect recurrent disease.

PMID: 32191683 [PubMed - in process]

Long-standing Sporadic Pancreatic Insulinoma: Report of a Rare Case.

Fetched: March 21st, 2020, 5:01am GMT

Long-standing Sporadic Pancreatic Insulinoma: Report of a Rare Case.

Cureus. 2020 Feb 11;12(2):e6947

Authors: Majid Z, Tahir F, Haider SA

Abstract
Insulinomas are rare, functional pancreatic neuroendocrine tumors arising from the pancreatic multipotent stem cells or neuroendocrine islet, occurring with a higher proportion in females. Majority of insulinomas have a sporadic etiology; however, only 5%-10% develop as a part of multiple endocrine neoplasm type 1 syndrome. They usually present with symptoms of hypoglycemia including disturbance in orientation, tremors, diaphoresis, altered mental state, seizures and visual changes among others. The diagnosis is based on appreciation of the classic Whipple triad, i.e. neuroglycopenic symptoms and sympathetic drive along with low serum glucose levels (<50 mg/dL) and a complete reversibility of these symptoms with prompt administration of glucose. The gold standard treatment for insulinoma involves complete surgical excision (i.e. enucleation), which is curative in 90% of the patients. Health care physicians should have a high index of suspicion for this tumor in patients presenting with neurological and sympathetic symptoms, particularly if they are resolved after eating. Here, we report the case of a 48-year-old female with the history of multiple episodes of hypoglycemic symptoms for the past two years which improved on glucose intake. Furthermore, we also summarized the discussion regarding diagnosis and management of pancreatic insulinoma.

PMID: 32190498 [PubMed]

Hypercalcemia in a Patient Diagnosed with a Vasoactive Intestinal Peptide Tumor.

Fetched: March 21st, 2020, 5:01am GMT

Hypercalcemia in a Patient Diagnosed with a Vasoactive Intestinal Peptide Tumor.

Cureus. 2020 Feb 04;12(2):e6882

Authors: Ataallah B, Buttar BS, Kulina G, Kaell A

Abstract
Hypercalcemia is a clinical problem that is commonly seen in both the inpatient and outpatient settings. Overall, most common causes of hypercalcemia include hyperparathyroidism and malignancy. Our case report is the presentation of hypercalcemia in a patient eventually diagnosed with a vasoactive intestinal peptide tumor, a type of neuroendocrine tumor, without associated hyperparathyroidism.

PMID: 32190445 [PubMed]

Atypical carcinoid: A rare finding of a man with mediastinal mass: A case report.

Fetched: March 21st, 2020, 5:01am GMT

Atypical carcinoid: A rare finding of a man with mediastinal mass: A case report.

Mol Clin Oncol. 2020 Apr;12(4):325-328

Authors: Xuan WX, Li JJ, Shi YJ, Zhang XJ

Abstract
The present case report describes a case of mediastinal atypical carcinoid and a favorable outcome linked with the treatment. Mediastinal atypical carcinoid is a rare and aggressive type of neuroendocrine tumor. A 56-year-old man was admitted at the Respiratory Department due to intermittent tightness of the chest for 1 month. An initial diagnosis of a mass in the left anterior mediastinum was conducted using CT scan and immunohistochemistry. Laboratory data revealed the following values: Neuron Specific Enolase of 62.13 ng/ml (reference range, 0-40 ng/ml); CYFRA21 of 3.01 ng/ml (reference range, 0-3.3 ng/ml); CEA of 4.22 (0-6.5) ng/ml; SCC of 0.5 (0-1.5) ng/ml; CA125 of 67.24 (0-35) U/ml; AFP of 23 (0-25) U/ml; CRP of 96.7 (0-10) mg/l; PCT <0.05 (0-0.05) ng/ml; and ESR of 48 (0-20) mm/h. Tissue pathology revealed tumor cells with small cell pattern, and cell proliferation activity was 10%. Combined chemotherapy with bevacizumab (0.4 g, qd, once every 21 days) and capecitabine (0.15 g, Bid, Po) and timozolamine (0.34 mg, qd, po) was administered for 6 cycles. After the patient was given chemotherapy, the symptoms and CT exhibited improvement. On March 11, 2018, the lesion progressed into the lymph and pleura. The patient was commenced on radiotherapy and new chemotherapeutic regimen etoposide (0.5 g)-carboplatin (0.4 g)-bevacate (0.4 g). Another CT scan was performed after a month which revealed a substantial decrease in tumor size. Hence, a CT scan was performed for this patient who further revealed a decrease in tumor size. Currently patients are treated with bevacizumab maintenance therapy. Further studies of conservative treatment of chemotherapy and radiotherapy may provide a treatment to improve atypical carcinoid.

PMID: 32190314 [PubMed]

Permalink for 'Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.'

Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

Fetched: March 21st, 2020, 5:01am GMT

Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

Int J Endocrinol. 2020;2020:9287536

Authors: Mansoor W, Ferguson S, Ross V, Talbot D

Abstract
There is inconsistency among published guidelines for the optimal diagnostic and management pathways for patients with typical (TC) or atypical (AC) pulmonary carcinoid tumours. We conducted a UK-wide clinician survey to assess current practice for the diagnosis, management, and follow-up of patients with TC/AC and descriptively compared management between European Neuroendocrine Tumor Society (ENETS) accredited centres of excellence (CoE) and nonaccredited centres (non-CoE). Twenty-seven clinicians (10 CoE; 17 non-CoE) participated. Computed tomography of thorax, abdomen, and pelvis was the most commonly reported diagnostic tool (96% of respondents), and bone scans and gallium somatostatin receptor scintigraphy positron emission tomography (SRS PET) were the least commonly reported (30% and 37% of respondents, respectively). Adjuvant therapy is considered for resected TC/AC by <5% of respondents for patients with stage N0 M0 AC or TC, up to 48% of respondents for patients with AC with R1 disease. Somatostatin analogues were the most commonly reported first-line treatment (63% of respondents), and chemotherapy was the most commonly reported second-line therapy and third-line therapy (33% and 41%, respectively) for unresectable and metastatic disease. Reported frequency of initial follow-up after primary surgery ranged from every 2 months to annual, and total follow-up duration ranged from 2 years to indefinite depending on disease type (TC/AC) and stage. For most diagnostic investigations, the highest reported frequency of use was in CoE, most notably gallium SRS PET (70% CoE vs. 18% non-CoE respondents). 93% of respondents (100% CoE; 88% non-CoE) reported having neuroendocrine tumour- (NET-) specialist multidisciplinary team meetings at their centre; 59% (90% CoE; 41% non-CoE) had a NET Clinical Nurse Specialist (CNS) and 48% (80% CoE; 29% non-CoE) had a lung NET patient database. The survey results suggest variability between UK centres in diagnostic pathways and management of patients with TC/AC and suggest that CoE may be able to offer an improved service to patients.

PMID: 32190050 [PubMed]

Permalink for '68Ga-DOTATATE positron emission tomography/computed tomography to detect the recurrence of phosphaturic mesenhcymal tumor-induced osteomalacia.'

68Ga-DOTATATE positron emission tomography/computed tomography to detect the recurrence of phosphaturic mesenhcymal tumor-induced osteomalacia.

Fetched: March 21st, 2020, 5:01am GMT

68Ga-DOTATATE positron emission tomography/computed tomography to detect the recurrence of phosphaturic mesenhcymal tumor-induced osteomalacia.

World J Nucl Med. 2020 Jan-Mar;19(1):78-81

Authors: Bhalla MI, Wirtz KM, Fair ES, Bucklan DJ

Abstract
68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) has shown superiority over 111Indium-octreotide scanning for the detection of phosphaturic mesenchymal tumors (PMTs). We report a case of tumor-induced osteomalacia resulting from PMT which, although initially clinically suspected, was not localized on octreotide scintigraphy performed several years prior. Subsequent surgical excision of a presumed benign osseous lesion a few years later revealed the diagnosis on pathology. Imaging assessment using 68Ga-DOTATATE PET/CT following recent clinical suspicion for recurrence revealed an intense tracer-avid lesion at the primary tumor site. DOTATATE imaging plays an important role in localizing tumors with high somatostatin receptor expression, such as neuroendocrine tumors (pheochromocytoma, paraganglioma, and neuroblastoma), meningioma, and mesenchymal tumors, causing oncogenic osteomalacia.

PMID: 32190030 [PubMed]

Permalink for 'ASO Author Reflections: Uninsurance is Associated with Worse Outcomes Following Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.'

ASO Author Reflections: Uninsurance is Associated with Worse Outcomes Following Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.

Fetched: March 21st, 2020, 5:01am GMT

ASO Author Reflections: Uninsurance is Associated with Worse Outcomes Following Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.

Ann Surg Oncol. 2020 Mar 18;:

Authors: Marincola Smith P, Baechle JJ, Idrees K

PMID: 32189167 [PubMed - as supplied by publisher]

FGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice.

Fetched: March 20th, 2020, 5:01am GMT

FGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice.

Cell Rep. 2020 Mar 17;30(11):3837-3850.e3

Authors: Ferone G, Song JY, Krijgsman O, van der Vliet J, Cozijnsen M, Semenova EA, Adams DJ, Peeper D, Berns A

Abstract
Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified in human small-cell lung cancer (SCLC), but its contribution to SCLC and other lung tumors has remained elusive. Here, we assess the tumorigenic capacity of constitutive-active FGFR1 (FGFR1K656E) with concomitant RB and P53 depletion in mouse lung. Our results reveal a context-dependent effect of FGFR1K656E: it impairs SCLC development from CGRPPOS neuroendocrine (NE) cells, which are considered the major cell of origin of SCLC, whereas it promotes SCLC and low-grade NE bronchial lesions from tracheobronchial-basal cells. Moreover, FGFR1K656E induces lung adenocarcinoma (LADC) from most lung cell compartments. However, its expression is not sustained in LADC originating from CGRPPOS cells. Therefore, cell context and tumor stage should be taken into account when considering FGFR1 inhibition as a therapeutic option.

PMID: 32187553 [PubMed - in process]

Permalink for 'Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group.'

Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group.

Fetched: March 20th, 2020, 5:01am GMT

Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group.

J Surg Oncol. 2020 Mar 17;:

Authors: Heidsma CM, Hyer M, Tsilimigras DI, Rocha F, Abbott DE, Fields R, Smith PM, Poultsides GA, Cho C, Maithel SK, Pawlik TM, Other Members of the US Neuroendocrine Tumor Study Group

Abstract
BACKGROUND AND OBJECTIVES: We sought to define the incidence and impact of Textbook Outcome (TO) on disease-free survival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET).
METHODS: Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade ≥ III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, > 75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined.
RESULTS: Among 821 patients with a PNET, median tumor size was 2.1 cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n = 231, 28.1%), distal pancreatectomy (DP) (n = 492, 59.9%), and enucleation (EN) (n = 98, 11.9%). Overall TO rate was 49.3% (n = 405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P < .001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35-0.81; P = .003).
CONCLUSIONS: Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.

PMID: 32185804 [PubMed - as supplied by publisher]

Primary Neuroendocrine Tumor of the Thymus: Radiological and Pathological Correlation.

Fetched: March 20th, 2020, 5:01am GMT

Primary Neuroendocrine Tumor of the Thymus: Radiological and Pathological Correlation.

J Radiol Case Rep. 2020 Jan;14(1):1-11

Authors: Berman K, Kirsch J, Bejarano P, Drexler I, Martinez F

Abstract
Primary neuroendocrine tumors of the thymus are extremely rare. In this report, we describe a case of a 69 year-old man with an intermediate grade thymic neuroendocrine tumor. The radiologic and histopathologic features of thymic neuroendocrine tumors are discussed with reference to relevant literature.

PMID: 32184929 [PubMed - in process]

Permalink for 'Metronidazole induced encephalopathy: case report and discussion on the differential diagnoses, in particular, Wernicke's encephalopathy.'

Metronidazole induced encephalopathy: case report and discussion on the differential diagnoses, in particular, Wernicke's encephalopathy.

Fetched: March 20th, 2020, 5:01am GMT

Metronidazole induced encephalopathy: case report and discussion on the differential diagnoses, in particular, Wernicke's encephalopathy.

J Radiol Case Rep. 2019 Sep;13(9):1-7

Authors: Hou W, Yiin RSZ, Goh CK

Abstract
Metronidazole induced encephalopathy is a rare central nervous system toxicity, which may be completely reversible with prompt cessation of metronidazole usage. We present a case of metronidazole induced encephalopathy in a 59-year-old man with a history of Whipple's procedure for pancreatic neuroendocrine tumour. The characteristic magnetic resonance imaging features of metronidazole induced encephalopathy and its main differential diagnosis, Wernicke's encephalopathy, are discussed.

PMID: 32184926 [PubMed - in process]

A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer.

Fetched: March 20th, 2020, 5:01am GMT

A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer.

Nat Commun. 2020 Mar 17;11(1):1320

Authors: Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M, Nakayama KI

Abstract
Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment.

PMID: 32184390 [PubMed - in process]

Imaging Features and Patterns of Metastasis in Non-Small Cell Lung Cancer with RET Rearrangements.

Fetched: March 20th, 2020, 5:01am GMT

Imaging Features and Patterns of Metastasis in Non-Small Cell Lung Cancer with RET Rearrangements.

Cancers (Basel). 2020 Mar 15;12(3):

Authors: Digumarthy SR, Mendoza DP, Lin JJ, Rooney M, Do A, Chin E, Yeap BY, Shaw AT, Gainor JF

Abstract
Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET, ALK, or ROS1 gene fusion (RET = 32; ALK = 116; ROS1 = 67). Patients with RET+ NSCLC were older at presentation compared to ALK+ and ROS1+ patients (median age: RET = 64 years; ALK = 51 years, p < 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology (RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET+ patients were more likely to be peripheral (RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1+ NSCLC (RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET+ NSCLC shares several distinct radiologic features and metastatic spread with ALK+ and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.

PMID: 32183422 [PubMed]

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1.

Fetched: March 20th, 2020, 5:01am GMT

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1.

Cancers (Basel). 2020 Mar 14;12(3):

Authors: Luley KB, Biedermann SB, Künstner A, Busch H, Franzenburg S, Schrader J, Grabowski P, Wellner UF, Keck T, Brabant G, Schmid SM, Lehnert H, Ungefroren H

Abstract
Experimental models of neuroendocrine tumor disease are scarce, with only a few existing neuroendocrine tumor cell lines of pancreatic origin (panNET). Their molecular characterization has so far focused on the neuroendocrine phenotype and cancer-related mutations, while a transcription-based assessment of their developmental origin and malignant potential is lacking. In this study, we performed immunoblotting and qPCR analysis of neuroendocrine, epithelial, developmental endocrine-related genes as well as next-generation sequencing (NGS) analysis of microRNAs (miRs) on three panNET cell lines, BON-1, QGP-1, and NT-3. All three lines displayed a neuroendocrine and epithelial phenotype; however, while insulinoma-derived NT-3 cells preferentially expressed markers of mature functional pancreatic β-cells (i.e., INS, MAFA), both BON-1 and QGP-1 displayed high expression of genes associated with immature or non-functional β/δ-cells genes (i.e., NEUROG3), or pancreatic endocrine progenitors (i.e., FOXA2). NGS-based identification of miRs in BON-1 and QGP-1 cells revealed the presence of all six members of the miR-17-92 cluster, which have been implicated in b-cell function and differentiation, but also have roles in cancer being both oncogenic or tumor suppressive. Notably, both BON-1 and QGP-1 cells expressed several miRs known to be negatively associated with epithelial-mesenchymal transition, invasion or metastasis. Moreover, both cell lines failed to exhibit migratory activity in vitro. Taken together, NT-3 cells resemble mature functional β-cells, while both BON-1 and QGP-1 are more similar to immature/non-functional pancreatic β/δ-cells or pancreatic endocrine progenitors. Based on the recent identification of three transcriptional subtypes in panNETs, NT-3 cells resemble the "islet/insulinoma tumors" (IT) subtype, while BON-1 and QGP-1 cells were tentatively classified as "metastasis-like/primary" (MLP). Our results provide a comprehensive characterization of three panNET cell lines and demonstrate their relevance as neuroendocrine tumor models.

PMID: 32183367 [PubMed]

Permalink for 'Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study.'

Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study.

Fetched: March 20th, 2020, 5:01am GMT

Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study.

Biology (Basel). 2020 Mar 09;9(3):

Authors: Koumarianou A, Pectasides D, Koliou GA, Dionysopoulos D, Kolomodi D, Poulios C, Skondra M, Sgouros J, Pentheroudakis G, Kaltsas G, Fountzilas G

Abstract
The purpose of this study was to explore the efficacy and safety of everolimus administered as a first-line treatment in newly diagnosed patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP NETs). This phase II, multicenter, single-arm study included patients with well-differentiated GEP NETs and a Ki67 < 20%. Everolimus, at 10 mg/day, was administered until disease progression; 18 patients (72%) concomitantly received octreotide long-acting release (LAR), at 30 mg/month. The primary endpoint was the 15-month progression-free survival (PFS) rate. Twenty-five patients (grade 1: 11 patients, grade 2: 14 patients) were enrolled between August 2012 and October 2015. At a median follow-up of 58.1 months, the median PFS was 14.6 months, while the 15-month PFS rate was 48%; median overall survival had not been reached yet. Normal baseline chromogranin A (<4 nmol/l) confirmed a longer PFS (HR = 0.25, 95% CI 0.08-0.77, p = 0.016). Seven patients (28%) achieved an objective response (one complete response and six partial responses) in a median of 2.6 months. Twenty-three grade 3-4 events were recorded (14 patients). No fatal reactions occurred. This prospective phase II study unravels the notable activity of everolimus as a first-line treatment in patients with GEP NETS and contributes valuable information about the high activity of the combination of everolimus and octreotide LAR in this setting. Clinical trial information: NCT01648465.

PMID: 32182791 [PubMed]

[Skin cancers in Madagascar: where do we stand?]

Fetched: March 20th, 2020, 5:01am GMT

[Skin cancers in Madagascar: where do we stand?]

Pan Afr Med J. 2019;34:167

Authors: Malalaniaina A, Lovasoa T, Mamisoa RI, Malala R, Soavina RL, Florine R, Fahafahantsoa RR

Abstract
Introduction: Skin cancers are malignant keratinizing tumors of epidermal, melaninic or adnexal origin. These cancers are still little known. However they affect people living in Madagascar where the amount of sunshine remains very high with an impact that varies depending on the skin type. The purpose of our study was to determine the epidemio-clinical profile of skin cancers in Antananarivo.
Methods: We conducted a retrospective descriptive study of skin cancers in the Department of Oncology of the Joseph Ravoahangy Andrianavalona Hospital, Antananarivo over a period of seven years. It included patients with tumoral skin lesions confirmed by histological examination.
Results: We collected data from 47 cases of skin cancers (male predominance; sex ratio 1.13). The average age of patients was 49.3 years. Farmers were the most affected. The lesions mainly occurred in the head, neck (44%) and lower limbs (42%). Localized skin cancers were detected in 61.7% of cases. Squamous cell carcinoma was the most common skin cancer in Madagascar (37%), followed by the melanoma (21%) and the basal cell carcinoma (11%). Treatment was mainly based on surgery (74.19%).
Conclusion: Squamous cell carcinoma is the most common cancer in Madagascar, followed by melanoma and basal cell carcinoma. Skin cancers affect mainly the young population and require appropriate management.

PMID: 32153707 [PubMed - indexed for MEDLINE]

Suppression of tumor growth and metastasis by ethanol extract of Angelica dahurica Radix in murine melanoma B16F10 cells.

Fetched: March 20th, 2020, 5:01am GMT

Suppression of tumor growth and metastasis by ethanol extract of Angelica dahurica Radix in murine melanoma B16F10 cells.

Biosci Trends. 2020 Mar 16;14(1):23-34

Authors: Hwangbo H, Choi EO, Kim MY, Kwon DH, Ji SY, Lee H, Hong SH, Kim GY, Hwang HJ, Hong SH, Choi YH

Abstract
The roots of Angelica dahurica have long been used as a traditional medicine in Korea to treat various diseases such as toothache and cold. In this study, we investigated the effect of ethanol extract from the roots of this plant on metastatic melanoma, a highly aggressive skin cancer, in B16F10 melanoma cells and B16F10 cell inoculated-C57BL/6 mice. Our results showed that the ethanol extracts of Angelicae dahuricae Radix (EEAD) suppressed cell growth and induced apoptotic cell death in B16F10 cells. EEAD also activated the mitochondria-mediated intrinsic apoptosis pathway, with decreased mitochondrial membrane potential, and increased production of intracellular reactive oxygen species and ration of Bax/Bcl-2 expression. Furthermore, EEAD reduced the migration, invasion, and colony formation of B16F10 cells through the reduced expression and activity of matrix metalloproteinase (MMP)-2 and -9. In addition, in vivo results demonstrated that oral administration of EEAD inhibited lactate dehydrogenase activity, hepatotoxicity, and nephrotoxicity without weight loss in B16F10 cell inoculated-mice. Importantly, EEAD was able to markedly suppress lung hypertrophy, the incidence of B16F10 cells lung metastasis, and the expression of tumor necrosis factor-alpha in lung tissue. Taken together, our findings suggest that EEAD may be useful for managing metastasis and growth of malignant cancers, including melanoma.

PMID: 32092745 [PubMed - indexed for MEDLINE]

Occurrences and Outcomes of Immune Checkpoint Inhibitors-Induced Vitiligo in Cancer Patients: A Retrospective Cohort Study.

Fetched: March 20th, 2020, 5:01am GMT

Occurrences and Outcomes of Immune Checkpoint Inhibitors-Induced Vitiligo in Cancer Patients: A Retrospective Cohort Study.

Drug Saf. 2020 02;43(2):111-117

Authors: Babai S, Voisin AL, Bertin C, Gouverneur A, Le-Louet H

Abstract
BACKGROUND: The use of immune checkpoint inhibitors (ICI) in melanoma and non-small cell lung cancer patients is associated with the onset of vitiligo. However, previous studies have suggested conflicting results on the conditions of occurrence of ICI-induced vitiligo.
OBJECTIVE: The aim of this study was to describe the occurrences and outcomes of several cases of ICI-induced vitiligo.
METHODS: A retrospective study was carried out using the French Pharmacovigilance Database (FPD) between the beginning of the commercialization of ICI in France and 1 January 2019, selecting for analysis the vitiligo reactions of patients due to treatment with ICI.
RESULTS: Among the 95 case patients identified in the FPD, the median times to onset of vitiligo after the start of pembrolizumab, nivolumab and ipilimumab therapies were 5.4, 5.0, and 3.8 months, respectively. Furthermore, 37 patients (45%) discontinued ICI treatment due to disease progression. The median follow-up time of all patients was 33 months (interquartile range 2-56).
CONCLUSIONS: This study provided an overall picture of ICI-induced vitiligo in daily medical practice on a large number of pharmacovigilance observations of case patients. Among the observations of ICI-induced vitiligo, the diagnosed cancer was melanoma for almost all patients. Most patients in the study experienced other associated adverse drug reactions (ADRs), such as colitis, pruritus, hypothyroidism, hyperthyroidism, thyroiditis, pancreatitis, and gastritis. Furthermore, our data suggest that the resolution of pembrolizumab- or nivolumab-induced vitiligo could be a marker of disease progression. Future studies evaluating vitiligo outcomes are warranted.

PMID: 31630381 [PubMed - indexed for MEDLINE]

Patient experiences with isolated limb perfusion for malignant melanoma - A qualitative study.

Fetched: March 20th, 2020, 5:01am GMT

Patient experiences with isolated limb perfusion for malignant melanoma - A qualitative study.

Eur J Oncol Nurs. 2019 12;43:101672

Authors: Ekenberg M, Wesslau H, Olofsson Bagge R, Engström M

Abstract
PURPOSE: In recent years, the incidence of malignant melanoma has rapidly increased worldwide. Among patients with recurrences, approximately 5% develop in-transit metastases, which can potentially be treated with isolated limb perfusion (ILP). However, little is known about patient experiences with this treatment. A more thorough understanding might guide future research and clinical care. In this study, we aimed to describe patients' experiences of ILP treatment.
METHODS: This study included eight patients who participated in a semi-structed interviewed, conducted at one occasion between 3 and 11 months after their ILP treatment. The mean interview duration was 26 min. Data were analyzed using qualitative inductive content analysis according to the methods of Elo-Kyngäs and Graneheim and Lundman.
RESULTS: Our analysis yielded three categories, each built on two subcategories: positive experiences after ILP treatment emerged from the sub-categories reduced tumor burden and living a less restricted life; negative experiences after ILP was built on the subcategories fear of relapse and complications and side effects; and experiences of healthcare was founded on the subcategories need for correct information and being viewed as sicker then experienced.
CONCLUSION: Participants showed greater focus on the healthy parts of their lives, even when negative symptoms occurred after ILP treatment. They also described how healthcare workers focused on their illness. Based on these findings, we suggest the following means of providing good nursing care to ILP patients: give correct information, strive to reduce patients' negative symptoms, support their daily living needs, and provide emotional support to reduce fear of recurrence.

PMID: 31614318 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.

Fetched: March 20th, 2020, 5:01am GMT

Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.

Microb Pathog. 2019 Dec;137:103778

Authors: Arora R, Rekhi B, Chandrani P, Krishna S, Dutt A

Abstract
Merkel cell carcinoma is a rare, lethal cancer histopathologically composed of cells showing similarity with mechanoreceptor Merkel cells. Merkel cell tumors manifest in two distinct forms. While a virus called Merkel cell polyomavirus is involved in the pathogenesis of one form of Merkel tumors, the other is driven by ultraviolet (UV)-linked mutations. In this study we investigated 18 cases, from the Indian population, of Merkel cell carcinoma for immunohistochemical (IHC) expression of Merkel cell polyomavirus (MCV) T antigen, including 12 cases tested by PCR, to identify viral etiopathology. We tested the tumors with two sensitive antibodies (CM2B4 and Ab3), targeting the viral large T antigen protein and with PCR primers targeting the N terminus of T antigen. Overall, we observed 38.8% (7/18) tumors displaying positive IHC expression of Merkel cell polyomavirus T antigen and 25% (3/12) tumors showing positive results, by both, immunohistochemistry and PCR. This constitutes the first report from India showing implication of MCV in Merkel cell carcinomas. Moreover, this is one of the larger series of Merkel cell carcinomas, tested for MCV, by both immunohistochemistry and PCR, in this part of the world. These results further indicate that a slightly more number of such cases in India are likely to be caused by UV-linked damage, as opposed to Merkel cell polyomavirus mediated tumorigenesis, which is definitely implicated in a subset of cases.

PMID: 31600537 [PubMed - indexed for MEDLINE]

Permalink for 'Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells.'

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells.

Fetched: March 20th, 2020, 5:01am GMT

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells.

Biochem J. 2019 09 10;476(17):2463-2486

Authors: Martínez J, Tarallo D, Martínez-Palma L, Victoria S, Bresque M, Rodríguez-Bottero S, Marmisolle I, Escande C, Cassina P, Casanova G, Bollati-Fogolín M, Agorio C, Moreno M, Quijano C

Abstract
Cellular senescence is an endpoint of chemotherapy, and targeted therapies in melanoma and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and an enhanced mitochondrial energy metabolism supports resistance to therapy in melanoma cells. Herein, we assessed the mitochondrial function of therapy-induced senescent melanoma cells obtained after exposing the cells to temozolomide (TMZ), a methylating chemotherapeutic agent. Senescence induction in melanoma was accompanied by a substantial increase in mitochondrial basal, ATP-linked, and maximum respiration rates and in coupling efficiency, spare respiratory capacity, and respiratory control ratio. Further examinations revealed an increase in mitochondrial mass and length. Alterations in mitochondrial function and morphology were confirmed in isolated senescent cells, obtained by cell-size sorting. An increase in mitofusin 1 and 2 (MFN1 and 2) expression and levels was observed in senescent cells, pointing to alterations in mitochondrial fusion. Silencing mitofusin expression with short hairpin RNA (shRNA) prevented the increase in mitochondrial length, oxygen consumption rate and secretion of interleukin 6 (IL-6), a component of the SASP, in melanoma senescent cells. Our results represent the first in-depth study of mitochondrial function in therapy-induced senescence in melanoma. They indicate that senescence increases mitochondrial mass, length and energy metabolism; and highlight mitochondria as potential pharmacological targets to modulate senescence and the SASP.

PMID: 31431479 [PubMed - indexed for MEDLINE]

Upregulation of S100A9 contributes to the acquired resistance to BRAF inhibitors.

Fetched: March 20th, 2020, 5:01am GMT

Upregulation of S100A9 contributes to the acquired resistance to BRAF inhibitors.

Genes Genomics. 2019 11;41(11):1273-1280

Authors: Hwang SH, Ahn JH, Lee M

Abstract
BACKGROUNDS: Acquired resistance is a significant clinical challenge in targeted therapy of melanomas using BRAF inhibitors. We previously identified that downregulation of miR-92a-1-5p confers acquired resistance to BRAF inhibition using an miRNA array platform.
OBJECTIVE: In this study, we investigated the target genes of miR-92a-1-5p and their functional significance in BRAF inhibitor resistance.
METHODS: The miRNA target prediction data were combined with RNA-Seq data to identify possible target genes for miR-92a-1-5p. Cellular effects of target genes were further examined using siRNA knockdown, WST-1 assay, and immunoblotting analysis.
RESULTS: We selected S100 calcium-binding protein A9 (S100A9) as a possible target gene for functional validation. S100A9 knockdown abrogated resistance to PLX4720 in A375P/Mdr cells. This result was similar to those described earlier for miR-92a-1-5p, indicating that miR-92a-1-5p inhibits cell viability by targeting S100A9. S100A9 overexpression partially conferred PLX4720 resistance to A375P cells. We also demonstrated that MAPK re-activation does not contribute to the promotion of BRAF inhibitor resistance by S100A9.
CONCLUSION: Taken together, our results indicate that S100A9 might be functionally involved in development of resistance to BRAF inhibitors and might be a target for melanoma therapy in the future.

PMID: 31388978 [PubMed - indexed for MEDLINE]

Permalink for 'Well-differentiated grade 3 neuroendocrine tumours and poorly differentiated grade 3 neuroendocrine carcinomas: will dual tracer PET-computed tomography (68Ga-DOTATATE and FDG) play a pivotal role in differentiation and guiding management strategies?'

Well-differentiated grade 3 neuroendocrine tumours and poorly differentiated grade 3 neuroendocrine carcinomas: will dual tracer PET-computed tomography (68Ga-DOTATATE and FDG) play a pivotal role in differentiation and guiding management strategies?

Fetched: March 20th, 2020, 5:01am GMT

Well-differentiated grade 3 neuroendocrine tumours and poorly differentiated grade 3 neuroendocrine carcinomas: will dual tracer PET-computed tomography (68Ga-DOTATATE and FDG) play a pivotal role in differentiation and guiding management strategies?

Nucl Med Commun. 2019 10;40(10):1086-1087

Authors: Basu S, Adnan A

PMID: 31365493 [PubMed - indexed for MEDLINE]

Permalink for 'Use of 3-dimensional computed tomography for planning a complex sleeve bronchoplasty with total parenchyma-sparing resection of a carcinoid tumour in the right main bronchus.'

Use of 3-dimensional computed tomography for planning a complex sleeve bronchoplasty with total parenchyma-sparing resection of a carcinoid tumour in the right main bronchus.

Fetched: March 20th, 2020, 5:01am GMT

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Use of 3-dimensional computed tomography for planning a complex sleeve bronchoplasty with total parenchyma-sparing resection of a carcinoid tumour in the right main bronchus.

Interact Cardiovasc Thorac Surg. 2019 10 01;29(4):638-640

Authors: Betser L, De Wolf J, Glorion M, Chapelier A

Abstract
Bronchoplasty is frequently required for radical resection of central typical carcinoid tumours. As sleeve bronchoplasty can be a complex procedure, an accurate evaluation of the tumour location is mandatory. Although the endobronchial part of the tumour can be easily evaluated by bronchoscopy, the exo-bronchial part is difficult to analyse with a standard computed tomography (CT) scan. A three-dimensional (3D) CT scan could be used to identify this exo-bronchial component of the tumour when planning a reconstruction. Herein, we present a case of a 59-year-old woman with a typical central carcinoid tumour of the right main bronchus. After 3D modelling, we successfully performed a total parenchyma-sparing resection with an intermedius bronchus reimplantation into the carina associated with the right upper bronchus anastomosis in the lateral trachea. The follow-up was uneventful. An endoscopy at 3 months showed excellent results.

PMID: 31115440 [PubMed - indexed for MEDLINE]

A phase 2 trial of sunitinib in patients with progressive paraganglioma or pheochromocytoma: the SNIPP trial.

Fetched: March 20th, 2020, 5:01am GMT

A phase 2 trial of sunitinib in patients with progressive paraganglioma or pheochromocytoma: the SNIPP trial.

Br J Cancer. 2019 06;120(12):1113-1119

Authors: O'Kane GM, Ezzat S, Joshua AM, Bourdeau I, Leibowitz-Amit R, Olney HJ, Krzyzanowska M, Reuther D, Chin S, Wang L, Brooks K, Hansen AR, Asa SL, Knox JJ

Abstract
BACKGROUND: Pheochromocytoma (PCC) and paraganglioma (PGL) are uncommon neoplasms with high morbidity in advanced stages. Effective systemic treatments are limited.
METHODS: A multisite phase 2 trial evaluated sunitinib in patients with progressive PCC/PGL. Patients received 50 mg orally for 4-6 weeks.
RESULTS: Between May 2009 and May 2016, 25 patients were enroled. The median age was 50 years and 56% were male. Three patients (12%) received prior chemotherapy and 16 (64%) prior surgery. The DCR was 83% (95% CI: 61-95%) and median PFS 13.4 (95% CI: 5.3-24.6) months. Of 23 evaluable patients, 3 (13%) with germline mutations (SDHA, SDHB, RET) achieved a PR. The patient with mutated RET and MEN2A remains on treatment after 64 cycles. The median time on treatment was 12.4 (1-88.0) months. Grade 3 or 4 toxicities were as expected and manageable; fatigue (16%) and thrombocytopenia (16%) were most common. One patient with grade 3 hypertension and 2 with grade 3 cardiac events discontinued treatment.
CONCLUSION: Although the primary endpoint of disease control was met, the overall response rate of sunitinib was low in unselected patients with progressive PCC/PGL. Patients with germline variants in RET or in the subunits of SDH may derive greatest benefit.

PMID: 31105270 [PubMed - indexed for MEDLINE]

Desmoplastic melanoma: a brief review and the efficacy of immunotherapy.

Fetched: March 20th, 2020, 5:01am GMT

Desmoplastic melanoma: a brief review and the efficacy of immunotherapy.

Expert Rev Anticancer Ther. 2019 03;19(3):205-207

Authors: Ochoa CE, Joseph RW

PMID: 30686076 [PubMed - indexed for MEDLINE]

Robotic enucleation of a pancreatic uncinate neuroendocrine tumor - a unique parenchyma-saving strategy for uncinate tumors.

Fetched: March 19th, 2020, 5:01am GMT

Robotic enucleation of a pancreatic uncinate neuroendocrine tumor - a unique parenchyma-saving strategy for uncinate tumors.

Ann Hepatobiliary Pancreat Surg. 2020 Feb;24(1):97-103

Authors: Chin KM, Goh BKP

Abstract
Pancreatic neuroendocrine tumors (PNET) comprise up to 10% of all pancreatic solid tumors. There has been much interest in recent years with regards to the role of limited resection and enucleation procedures for this entity. There is no clear guideline today on the optimal type choice of surgery for this condition, with even fewer reporting on the use of a robotic approach for pancreatic uncinate lesions. We describe a case report of a 54-year-old lady who underwent successful robotic enucleation of pancreatic uncinate neuroendocrine tumor. This patient's recovery was complicated by pancreatitis and a peripancreatic collection, both of which resolved without surgical re-intervention. A literature review was performed with regards to current guidelines on management of PNETs, comparisons between demolitive and parenchymal-preserving procedures, and recent developments in the laparoscopic and robotic approaches for this condition. There is no clear guideline on the optimal type and approach (open vs. laparoscopic vs. robotic) to the surgical management of PNET. We document in this case report a novel approach of robotic enucleation of pancreatic uncinate process NET, that could be considered as an alternative to open/laparoscopic demolitive procedures for small uncinate tumors.

PMID: 32181437 [PubMed]

Immune Checkpoint Markers in Neuroendocrine Carcinoma of the Digestive System.

Fetched: March 19th, 2020, 5:01am GMT

Immune Checkpoint Markers in Neuroendocrine Carcinoma of the Digestive System.

Front Oncol. 2020;10:132

Authors: Xing J, Ying H, Li J, Gao Y, Sun Z, Li J, Bai C, Cheng Y, Wu H

Abstract
Digestive system neuroendocrine carcinomas (NECs) are rare neoplasms originating from neuroendocrine cells with a poor prognosis and limited effective treatments. Programmed cell death protein 1/ligand 1 (PD-1/PD-L1) blockade has been used in the management of more than 10 solid tumors and has achieved promising clinical outcomes. PD-L1 expression, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) are all verified biomarkers that can predict the response to anti-PD-1/PD-L1 therapy. Here, we investigated PD-L1 expression and immune cell infiltration density by immunohistochemical (IHC) staining of tumor samples from 33 patients with digestive system NECs. Tumor and paratumor normal samples from 31 of these patients underwent whole-exome sequencing to evaluate TMB and the MSI-high (MSI-H) status. In total, 29.0% of digestive system NECs had positive PD-L1 expression according to the tumor proportion score (TPS). Infiltration of CD3+, CD8+, and CD68+ cells was observed in 69.7, 27.3, and 54.5% of patients, respectively. The TMB value for patients sequenced ranged from 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb. mSINGS, MSIsensor, and MSIseq were used to analyze the MSI status according to the sequencing data, and in our evaluation, no MSI-H status was detected. Our data might indicate a limited potential of anti-PD-1/PD-L1 monotherapy in digestive system NECs, although clinical trials are warranted.

PMID: 32181153 [PubMed]

Adrenal Adenoma Anarchy: A Case of an ACTH-Secreting Pheochromocytoma.

Fetched: March 19th, 2020, 5:01am GMT

Adrenal Adenoma Anarchy: A Case of an ACTH-Secreting Pheochromocytoma.

Case Rep Endocrinol. 2020;2020:4869467

Authors: Lee MN, Wan W, Chormanski DC, Kravchenko MI

Abstract
Introduction. Pheochromocytomas are rare neuroendocrine tumors that arise from sympathetic adrenomedullary chromaffin tissue. Depending on the amount of catecholamines they secrete, they have variable presentations. There have been reported cases of adrenocorticotrophic (ACTH) secreting pheochromocytomas that present with severe Cushing syndrome. Here, we present a pheochromocytoma with adrenocorticotrophic hormone (ACTH) cosecretion, which due to its rarity and variable presentation, may be a diagnostic challenge. Presentation. A 64-year-old woman with history of colon cancer presented with new-onset diabetes, worsening hot flashes, and hypertension. On CT imaging she had an enlarging right adrenal nodule (1.7 cm) with 60 Hounsfield units of attenuation and no PET avidity. Biochemical evaluation showed elevated urinary and plasma metanephrines, elevated plasma cortisol levels despite dexamethasone suppression, elevated late-night salivary cortisol, and high-normal adrenocorticotrophic hormone. The patient underwent laproscopic right adrenalectomy, and pathology confirmed pheochromocytoma. Her lab abnormalities and symptoms of hot flashes and hypertension improved postoperatively. Conclusion. This case demonstrates an unusual ACTH-secreting pheochromocytoma with subtle presentation and highlights the importance of obtaining a complete biochemical evaluation of incidental adrenal adenomas.

PMID: 32181024 [PubMed]

Neuroendocrine tumors of the urinary bladder A case series and review of the literature.

Fetched: March 19th, 2020, 5:01am GMT

Neuroendocrine tumors of the urinary bladder A case series and review of the literature.

Ann Ital Chir. 2020;91:65-68

Authors: Goret CC

Abstract
Neuroendocrine carcinoma cases, more frequent in the GI tract, have rarely been reported in extrapulmonary areas. Neuroendocrine carcinoma of the bladder is one of the malignancies with a poor prognosis, which is expected to cause rapid metastases. In addition, neuroendocrine carcinoma of the bladder constitutes < 1% of all bladder carcinomas. In this study, we present two rare cases, a combined small cell neuroendocrine carcinoma-high-grade urothelial carcinoma and a large cell neuroendocrine carcinoma, diagnosed at Çanakkale Onsekiz Mart University, Research and Practice Hospital Pathology Clinic, between November 2016 and January 2017. KEYWORDS: Bladder, L cell neuroendocrine carcinoma, Pathological features, Small cell neuroendocrine carcinoma.

PMID: 32180578 [PubMed - in process]

Primary neuroendocrine carcinoma of the breast: a 5-year experiences.

Fetched: March 19th, 2020, 5:01am GMT

Primary neuroendocrine carcinoma of the breast: a 5-year experiences.

Ann Ital Chir. 2020;91:23-26

Authors: Canbak T, Acar A, Tolan HK, Ozbagriacik M, Ezberci F

Abstract
PURPOSE: Breast neuroendocrine carcinomas constitute approximately 0.3-0.5% of all breast cancers. In this study, we aimed to evaluate the data of patients diagnosed with primary breast neuroendocrine carcinoma.
METHODS: Patients with more than 50% neuroendocrine differentiation identified in the histopathological examination between January 2010 and January 2015 and who had no other focus on imaging were evaluated retrospectively from the hospital registry system. Patients with secondary neuroendocrine tumor of the breast and male patients were excluded from the study. All patients gave informed consent. Patients were staged according to TNM classification.
RESULTS: During the study period, 425 patients were operated for breast cancer. Eleven patients were included in the study. The mean age of the patients was 68 (range 49-86). Immunohistochemical examinations revealed positive staining with neuron-specific enolase, synaptophysin and chromogranin in all patients. Ten patients had strong positive estrogen and progesterone receptors and receptor status was not specified in one patient. Distant organ metastasis was detected in 1 patient during the follow-up period, no local recurrence and mortality were seen in any patient.
CONCLUS ON: The most widely used specific markers of neuroendocrine differentiation are chromogranin and synaptophysin. There is no standard treatment protocol for primary breast neuroendocrine tumors. Most of the treatments reported in the literature and in this study are breast sparing surgery or mastectomy, followed by anthracycline and taxanebased chemotherapy and/or hormonotherapy, similar to the treatment of ductal carcinoma. The distinction of primary metastases in breast neuroendocrine tumors is important, so the presence of neuroendocrine tumors should be investigated in other organs. In this case the treatment is changed. The issue of how neuroendocrine differentiation affects clinical outcome is yet to be debated.
KEY WORDS: Chromogranin, Neuroendocrine tumor, Synaptophysin.

PMID: 32180568 [PubMed - in process]

Spontaneous rupture of a non-functioning pancreatic neuroendocrine tumor A case report of a rare cause of acute abdomen.

Fetched: March 19th, 2020, 5:01am GMT

Spontaneous rupture of a non-functioning pancreatic neuroendocrine tumor A case report of a rare cause of acute abdomen.

Ann Ital Chir. 2020;91:88-92

Authors: Achilli P, Chiarelli M, Giustizieri U, Burati M, Tagliabue F, Maternini M, Terragn S, Guttadauro A

Abstract
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors that account for 2% of all pancreatic malignancies, even though their incidence has been increasing over the past 20 years. Most PNETs are sporadic and tend to affect older individuals. Differently from functional tumors, which present with symptoms resulting from the specific hormone being elaborated, non-functioning pancreatic neuroendocrine tumors (NF-PNETs) typically present with symptoms related to local mass effect or metastatic disease. Today, due to the increasing use of abdominal imaging, NFPNETs are frequently discovered incidentally.
CASE REPORT: A 32-year-old woman was admitted to our emergency department for worsening upper abdominal pain radiating to the back. Shortly after the admission, shock and peritoneal signs developed. An abdominal computerized tomography scan showed a solid mass (9 x 12 cm) of the pancreatic tail with severe hemoperitomeum. Exploratory laparotomy and subsequent distal splenopancreasectomy were performed for a bleeding tumor. Histopathological report showed a neuroendocrine, well differentiated tumor (G1). The postoperative course was uneventful and the patient was successfully discharged on 10th postoperative day.
CONCLUSION: Spontaneous rupture of solid neuroendocrine neoplasms of the pancreas can cause acute abdomen with potentially devastating effects.
KEY WORDS: Abdominal pain, acute abdomen, Hemorrhagic shock, Pancreatic neuroendocrine tumor.

PMID: 32180565 [PubMed - in process]

Permalink for 'Endoscopic placement of pancreatic stent for "Deep" pancreatic enucleations operative technique and preliminary experience at two high-volume centers.'

Endoscopic placement of pancreatic stent for "Deep" pancreatic enucleations operative technique and preliminary experience at two high-volume centers.

Fetched: March 19th, 2020, 5:01am GMT

Endoscopic placement of pancreatic stent for "Deep" pancreatic enucleations operative technique and preliminary experience at two high-volume centers.

Surg Endosc. 2020 Mar 16;:

Authors: Giuliani T, Marchegiani G, Girgis MD, Crinò SF, Muthusamy VR, Bernardoni L, Pea A, Ramera M, Paiella S, Landoni L, Gabbrielli A, Salvia R, Donahue TR, Bassi C

Abstract
BACKGROUND: Pancreatic enucleation (PE) is a viable option for the removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, PE is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is close to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing PE. This paper describes a novel technique of "deep" PE preceded by endoscopic stenting of the MPD.
METHODS: From January 2017 to May 2019, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidates for PE with previous stenting of the MPD at the University of Verona, Italy, and at the UCLA Medical Center, Los Angeles, California. The endoscopic stenting was scheduled either the day before or 3 weeks before surgery, depending on the participating institute.
RESULTS: Ten patients were included in this pilot study. The endoscopic procedure was successful and well tolerated in all cases. Open, laparoscopic and robotic PE were performed. Seven patients had surgical complications. Among these, six developed a post-operative pancreatic fistula (POPF), but neither grade C fistulas nor disruptions of the MPD were detected. At pathology, a low grade pancreatic neuroendocrine tumor was confirmed in all cases.
CONCLUSION: In the setting of high-volume centers, this procedure is safe, and it is associated with acceptable short-term surgical morbidity. The preoperative stenting of the MPD might extend the surgical indications for PE.

PMID: 32180000 [PubMed - as supplied by publisher]

Outcomes of Simultaneous Resection of Small Bowel Neuroendocrine Tumors with Synchronous Liver Metastases.

Fetched: March 19th, 2020, 5:01am GMT

Outcomes of Simultaneous Resection of Small Bowel Neuroendocrine Tumors with Synchronous Liver Metastases.

World J Surg. 2020 Mar 16;:

Authors: Addeo P, Bertin JB, Imperiale A, Averous G, Terrone A, Goichot B, Bachellier P

Abstract
BACKGROUND: This study evaluated the short- and long-term outcomes of synchronous resection of liver metastases (LM) from small bowel neuroendocrine tumors (SB-NET).
METHODS: A retrospective review of patients undergoing resection for LMs from SB-NETs from January 1997 and December 2018 was performed.
RESULTS: There were 44 patients with synchronous SB-NET and LMs. Perioperative and 90-day mortality values were zero, and the morbidity rate was 27%. The median overall survival (OS) was 128.4 months (CI 95% 74.0-161.5 months) with 1-, 3-, 5-, and 10-year survival rates of 100%, 83%, 79%, and 60%, respectively. Not achieving surgical treatment for LM was the unique independent factor for survival (HR 6.50; CI 95% 1.54-27.28; p = 0.01) in patients with unresected LMs having OS and 10-year survival rates (42 months, 33%) versus patients undergoing liver resection (152 months, 66%)(p = 0.0008). The recurrence rate was 81.8% and associated with longer OS and 5-year survival rates when limited to the liver [223 months (61%) vs 94 months (87%)].
CONCLUSIONS: Simultaneous resection of SB-NETs with synchronous LMs was safe and associated with considerable long-term survival even in the presence of bilobar disease. However, recurrence after resection was common (81%) but associated with longer survival rates when limited to the liver.

PMID: 32179974 [PubMed - as supplied by publisher]

Permalink for 'Involvement of the γ1 subunit of the large-conductance Ca2+-activated K+ channel in the proliferation of human somatostatinoma cells.'

Involvement of the γ1 subunit of the large-conductance Ca2+-activated K+ channel in the proliferation of human somatostatinoma cells.

Fetched: March 19th, 2020, 5:01am GMT

Involvement of the γ1 subunit of the large-conductance Ca2+-activated K+ channel in the proliferation of human somatostatinoma cells.

Biochem Biophys Res Commun. 2020 Mar 13;:

Authors: Noda S, Chikazawa K, Suzuki Y, Imaizumi Y, Yamamura H

Abstract
Pancreatic neuroendocrine tumors (pNETs) occur due to the abnormal growth of pancreatic islet cells and predominantly develop in the duodenal-pancreatic region. Somatostatinoma is one of the pNETs associated with tumors of pancreatic δ cells, which produce and secrete somatostatin. Limited information is currently available on the pathogenic mechanisms of somatostatinoma. The large-conductance Ca2+-activated K+ (BKCa) channel is expressed in several types of cancer cells and regulates cell proliferation, migration, invasion, and metastasis. In the present study, the functional expression of the BKCa channel was examined in a human somatostatinoma QGP-1 cell line. In QGP-1 cells, outward currents were elicited by membrane depolarization at pCa 6.5 (300 nM) in the pipette solution and inhibited by the specific BKCa channel blocker, paxilline. Paxilline-sensitive currents were detected, even at pCa 8.0 (10 nM) in the pipette solution, in QGP-1 cells. In addition to the α and β2-4 subunits of the BKCa channel, the novel regulatory γ1 subunit (BKCaγ1) was co-localized with the α subunit in QGP-1 cells. Paxilline-sensitive currents at pCa 8.0 in the pipette solution were reduced by the siRNA knockdown of BKCaγ1. Store-operated Ca2+ entry was smaller in BKCaγ1 siRNA-treated QGP-1 cells. The proliferation of QGP-1 cells was attenuated by paxilline or the siRNA knockdown of BKCaγ1. These results strongly suggest that BKCaγ1 facilitates the proliferation of human somatostatinoma cells. Therefore, BKCaγ1 may be a novel therapeutic target for somatostatinoma.

PMID: 32178873 [PubMed - as supplied by publisher]

A rare serious case of retroperitoneal paraganglioma misdiagnosed as duodenal gastrointestinal stromal tumor: a case report.

Fetched: March 19th, 2020, 5:01am GMT

A rare serious case of retroperitoneal paraganglioma misdiagnosed as duodenal gastrointestinal stromal tumor: a case report.

BMC Surg. 2020 Mar 16;20(1):49

Authors: Mahmoud S, Salami M, Salman H

Abstract
BACKGROUND: Pheochromocytoma (PCC) and Paraganglioma (PGL) are rare neuroendocrine neoplasms. These tumors harbour disastrous consequences during surgery due to catecholamine hypersecretion if they are undiagnosed or prepared inadequately preoperatively.
CASE PRESENTATION: A 41- year- old lady presented with mild left flank discomfort. She had experienced recurrent anxiety attacks accompanied by palpitations and headache which were managed previously as panic attacks. Radiologic investigations showed a retroperitoneal mass that located anteromedial to the left kidney, separated from the left adrenal gland and adherent to the 4th duodenal segment. During admission, her vital signs showed slight elevation of blood pressure (140\90-160\110) mmHg, thus 24-h urine metanephrine and normetanephrine were requested and the results revealed normal values. Upper gastrointestinal endoscopy failed to pass beyond the 3th duodenal segment and showed no pathologic evidence. According to her findings, a diagnosis of duodenal gastrointestinal stromal tumor (GIST) was suspected. During laparotomy, crises of hypertension and tachycardia followed by severe hypotension made the resection of the misdiagnosed mass very tricky. Immunohistochemical staining studies confirmed the diagnosis of paraganglioma.
CONCLUSION: Paraganglioma is a life threatening disease and should always be considered as a differential diagnosis of asymptomatic retroperitoneal mass. The aim of our study is to present a challenging case of an undiagnosed retroperitoneal paraganglioma and to alarm our colleagues from such troubles.

PMID: 32178651 [PubMed - in process]

Permalink for 'Production, purification, and in vivo evaluation of a novel multiepitope peptide vaccine consisted of immunodominant epitopes of SYCP1 and ACRBP antigens as a prophylactic melanoma vaccine.'

Production, purification, and in vivo evaluation of a novel multiepitope peptide vaccine consisted of immunodominant epitopes of SYCP1 and ACRBP antigens as a prophylactic melanoma vaccine.

Fetched: March 19th, 2020, 5:01am GMT

Production, purification, and in vivo evaluation of a novel multiepitope peptide vaccine consisted of immunodominant epitopes of SYCP1 and ACRBP antigens as a prophylactic melanoma vaccine.

Int Immunopharmacol. 2019 Nov;76:105872

Authors: Safavi A, Kefayat A, Sotoodehnejadnematalahi F, Salehi M, Modarressi MH

Abstract
Melanoma cells are significantly resistance to the current treatments. Therefore, the best option for high-risk populations is prevention. Recently, many preventive cancer vaccines have been developed. In our previous study, several bioinformatic tools were employed for selection of the most immunodominant epitopes of acrosin binding protein (ACRBP) and synaptonemal complex protein 1 (SYCP1) antigens to design multiepitope DNA and peptide cancer vaccines. In the current study, the final construct of the multiepitope DNA vaccine was placed into a pcDNA3.1 vector and then, subcloned into a pET-28a (+) expression vector for transfecting BL21 E. coli strain. The recombinant multiepitope peptide vaccine, weighing 6.35 kDa, was purified by Fast protein liquid chromatography technique (FPLC) and detected by western blotting. Subsequently, C57BL/6 mice were immunized by a mixture of the peptide vaccine and incomplete Freund's adjuvant (IFA) (four vaccinations with one-week intervals). Two weeks after the last vaccination, the serum levels of the peptide-specific IgG total, IgG2a, and IgG1 were measured by enzyme-linked immunosorbent assays (ELISA). Also, the immunized mice splenocytes efficacy for producing interleukin-4 (IL-4) and interferon-γ (IFN-γ) after stimulation with the peptide vaccine was evaluated. At last, the prophylactic effect of the peptide vaccine immunization was evaluated in B16-F10 murine melanoma model. The peptide vaccine immunization caused a significant increase in the serum levels of IgG1, IgG2a, and IgG2a. Also, the immunized mice splenocytes exhibited significantly higher ability to produce IL-4 (10-fold) and IFN-γ (16-fold) after stimulation with the peptide vaccine, in comparison with the PBS and IFA groups. The peptide immunized mice exhibited 50.2% and 43% decrease in the mean tumors' volume in comparison with PBS and IFA groups. Also, the mean survival time for the peptide immunized mice was 33 ± 1.3 days which was 5 and 6 days more than the PBS and IFA groups, respectively. The obtained results exhibit high efficacy of the designed multiepitope peptide vaccine for the immune system activation and anti-tumor prophylactic effects in the murine melanoma model.

PMID: 31499268 [PubMed - indexed for MEDLINE]

[Primary central nervous system lymphoma following immunotherapy for metastatic melanoma].

Fetched: March 19th, 2020, 5:01am GMT

[Primary central nervous system lymphoma following immunotherapy for metastatic melanoma].

Ann Dermatol Venereol. 2019 Oct;146(10):634-639

Authors: Castel M, Cotten C, Deschamps-Huvier A, Commin MH, Marguet F, Jardin F, Duval-Modeste AB, Joly P

Abstract
BACKGROUND: Anti-PD-1 and anti-CTLA-4 monoclonal antibodies are used in melanoma, while anti-PD-1 are also used in Hodgkin's lymphoma. Primary central nervous system lymphoma is a rare form of non-Hodgkin's lymphoma with few effective treatments. However, several recent studies have reported multiple cases of non-Hodgkin's lymphoma and primary central nervous system lymphoma treated by anti-PD-1 antibodies with favourable responses.
PATIENTS AND METHODS: This study focuses on the case of a 59-year-old man with metastatic melanoma treated by immunotherapy (anti-CTLA-4 followed by anti-PD-1). He underwent 28 courses of therapy with pembrolizumab. Treatment was stopped after clinical and radiological remission. The patient presented left hemiparesis and a primary central nervous system lymphoma was diagnosed two months after discontinuation of immunotherapy. He started urgent high-dose methotrexate chemotherapy but without significant results. Despite second-line chemotherapy with R-ICE (rituximab-ifosfamide, carboplatin and etoposide), the patient died.
DISCUSSION: Several hypotheses may be advanced regarding a possible relationship between immunotherapy and the occurrence of this primary central nervous system lymphoma. The lymphoma may have been pre-existing and controlled by immunotherapy, but progressing rapidly after treatment, or it may have been induced by the immunotherapy. However, immunotherapy may have played no role; the relationship between melanoma and lymphoma is well known.
CONCLUSION: While immunotherapy cannot be unequivocally incriminated in primary central nervous system lymphoma, this case raises many questions about the imputability of immunotherapy in the occurrence of secondary cancers, including lymphomas.

PMID: 31122751 [PubMed - indexed for MEDLINE]

Permalink for 'p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.'

p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Fetched: March 19th, 2020, 5:01am GMT

p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Hum Mutat. 2019 07;40(7):926-937

Authors: Giacché M, Panarotto A, Tacchetti MC, Tosini R, Campana F, Mori L, Cappelli C, Pirola I, Lombardi D, Pezzola DC, Casella C, Castellano M

Abstract
Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease.

PMID: 30927507 [PubMed - indexed for MEDLINE]

Permalink for 'α-Tocopherol Succinate-Anchored PEGylated Poly(amidoamine) Dendrimer for the Delivery of Paclitaxel: Assessment of in Vitro and in Vivo Therapeutic Efficacy.'

α-Tocopherol Succinate-Anchored PEGylated Poly(amidoamine) Dendrimer for the Delivery of Paclitaxel: Assessment of in Vitro and in Vivo Therapeutic Efficacy.

Fetched: March 19th, 2020, 5:01am GMT

α-Tocopherol Succinate-Anchored PEGylated Poly(amidoamine) Dendrimer for the Delivery of Paclitaxel: Assessment of in Vitro and in Vivo Therapeutic Efficacy.

Mol Pharm. 2019 04 01;16(4):1541-1554

Authors: Bhatt H, Kiran Rompicharla SV, Ghosh B, Biswas S

Abstract
This study involves development of a dendrimer-based nanoconstruct by conjugating α-tocopheryl succinate (α-TOS) and polyethylene glycol (PEG) on a poly(amidoamine) dendrimer (G4 PAMAM) to improve intracellular delivery of a poorly water-soluble chemotherapeutic drug, paclitaxel (PTX). The conjugates were characterized by NMR, and PTX-loaded nanocarriers (G4-TOS-PEG-PTX) were evaluated for hydrodynamic diameter, polydispersity index (PDI), zeta potential, percentage encapsulation efficiency (%EE), and percentage drug loading (%DL). A hemolysis study was performed, which indicated that the synthesized dendrimer conjugates were not toxic to red blood cells; hence, they were biocompatible. A cellular uptake study in (B16F10 and MDA MB231) monolayer cells and 3D spheroids showed that α-TOS conjugation improved the time dependent uptake of nanosized dendrimer conjugates. The cell viability assay revealed that G4-TOS-PEG-PTX enhanced the cytotoxicity of PTX as compared to free PTX and PTX-loaded G4-PEG (G4-PEG-PTX) at tested concentrations. Correspondingly, the α-TOS-anchored dendrimer induced more apoptosis as compared to free PTX and G4-PEG-PTX. Moreover, the fluorescently labeled G4-TOS-PEG penetrated deeper into MDA MB231 3D spheroids as visualized by confocal microscopy. G4-TOS-PEG-PTX showed significant growth inhibition in 3D spheroids as compared to free PTX and G4-PEG-PTX. Further, the in vivo efficacy study using B16F10 xenografted C57Bl6/J mice indicated that the G4-TOS-PEG localized in tumor sections. G4-TOS-PEG-PTX reduced the tumor growth significantly compared to free PTX and G4-PEG-PTX. G4-TOS-PEG-PTX had more apoptotic potential in tumor sections as analyzed by TUNEL assay. Hence, the newly developed dendrimer conjugate, G4-TOS-PEG, has the potential to target loaded drug to the tumor, and G4-TOS-PEG-PTX has the potential to be utilized successfully in cancer treatment.

PMID: 30817166 [PubMed - indexed for MEDLINE]

Evaluation of a Novel Pb-203-Labeled Lactam-Cyclized Alpha-Melanocyte-Stimulating Hormone Peptide for Melanoma Targeting.

Fetched: March 19th, 2020, 5:01am GMT

Evaluation of a Novel Pb-203-Labeled Lactam-Cyclized Alpha-Melanocyte-Stimulating Hormone Peptide for Melanoma Targeting.

Mol Pharm. 2019 04 01;16(4):1694-1702

Authors: Yang J, Xu J, Cheuy L, Gonzalez R, Fisher DR, Miao Y

Abstract
The purpose of this study is to examine the melanocortin-1 receptor (MC1R) targeting and specificity of 203Pb-DOTA-GGNle-CycMSHhex in melanoma cells and tumors to facilitate its potential therapeutic application when labeled with 212Pb. The MC1R-specific targeting and imaging properties of 203Pb-DOTA-GGNle-CycMSHhex were determined on B16/F1 and B16/F10 murine melanoma cells and in B16/F1 flank melanoma-, B16/F10 flank melanoma-, and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. 203Pb-DOTA-GGNle-CycMSHhex displayed MC1R-specific binding on B16/F1 and B16/F10 melanoma cells and tumors. B16/F1 flank melanoma, B16/F10 flank melanoma, and B16/F10 pulmonary metastatic melanoma lesions could be clearly imaged by single photon emission computed tomography (SPECT) using 203Pb-DOTA-GGNle-CycMSHhex as an imaging probe. The favorable melanoma targeting and imaging properties highlighted the potential of 203Pb-DOTA-GGNle-CycMSHhex as a MC1R-targeting melanoma imaging probe and warranted the evaluation of 212Pb-DOTA-GGNle-CycMSHhex for melanoma therapy in future studies.

PMID: 30763112 [PubMed - indexed for MEDLINE]

177Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition.

Fetched: March 19th, 2020, 5:01am GMT

177Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition.

Endocr Relat Cancer. 2019 04 01;26(4):437-449

Authors: Hofving T, Sandblom V, Arvidsson Y, Shubbar E, Altiparmak G, Swanpalmer J, Almobarak B, Elf AK, Johanson V, Elias E, Kristiansson E, Forssell-Aronsson E, Nilsson O

Abstract
177Lu-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The 177Lu-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the 177Lu-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1,224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate <3.2×10-11). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of 177Lu-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of 177Lu-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of 177Lu-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.

PMID: 30730850 [PubMed - indexed for MEDLINE]

[Sigmoid intussusception as a clinical presentation of colonic schwannoma: Pediatric case].

Fetched: March 19th, 2020, 5:01am GMT

[Sigmoid intussusception as a clinical presentation of colonic schwannoma: Pediatric case].

Arch Argent Pediatr. 2019 02 01;117(1):e68-e71

Authors: González Ruiz Y, Reyes Delgado A, Gutiérrez Alonso C, Franco Rubio JI, González Herrero M

Abstract
Schwannomas are tumours originating in the Schwann cells of the peripheral nerves. The appearance in the colon is extremely rare, and there are no known cases in the literature of schwannomas of the colon and rectum described in children. These tumours are usually asymptomatic, but can produce non-specific and gastrointestinal symptoms. The clinical presentation as intestinal intussusception is infrequent. We present a case of an 11-year-old girl with sigmoid swchannoma presented clinically as a colonic intussusception with abdominal pain, rectal bleeding and constipation of 10 days. An intestinal resection with free surgical margins was performed.

PMID: 30652460 [PubMed - indexed for MEDLINE]

Arsenic May Act as a Pro-Metastatic Carcinogen Through Promoting Tumor Cell-Induced Platelet Aggregation.

Fetched: March 19th, 2020, 5:01am GMT

Arsenic May Act as a Pro-Metastatic Carcinogen Through Promoting Tumor Cell-Induced Platelet Aggregation.

Toxicol Sci. 2019 03 01;168(1):18-27

Authors: Kim K, Heo YK, Chun S, Kim CH, Bian Y, Bae ON, Lee MY, Lim KM, Chung JH

Abstract
Arsenic-associated carcinogenesis and related mortality are a major public health concern worldwide; however, the underlying mechanism of action remains unclear. Here, we demonstrated that arsenic promotes tumor metastasis by stimulating tumor cell-platelet aggregation (TCPA), which can ultimately increase cancer-related mortality. In freshly isolated human platelets in vitro, arsenic potentiated TCPA prompted by diverse cancer cell lines, which was attributable to increased platelet reactivity to TCPA with respect to thrombin generation and P-selectin, GPIIb/IIIa expression. Consistently, the co-existence of platelets and arsenic significantly enhanced tumor cell adhesion, extravasation and invasion along with increased metastasis-related markers like metallo-matrix proteinase-2 and -9 in vitro, which was attenuated by platelet activation blockers. Importantly, the exposure to arsenic-contaminated drinking water (2 ppm, 3 weeks) in mice in vivo significantly increased the metastasis of intravenously injected melanoma cells into lung. Furthermore, the exposure to arsenic-contaminated drinking water significantly reduced the survival of melanoma cell-injected mice, which was attenuated by the pretreatment of platelet-activation blockers; aspirin and eptifibatide. All these results provide an important clue to understand the mechanism underlying arsenic-associated cancer mortality and its prevention.

PMID: 30428081 [PubMed - indexed for MEDLINE]

Permalink for 'Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells.'

Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells.

Fetched: March 16th, 2020, 5:00am GMT

Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells.

Histochem Cell Biol. 2020 Mar 13;:

Authors: Kudoh S, Tenjin Y, Kameyama H, Ichimura T, Yamada T, Matsuo A, Kudo N, Sato Y, Ito T

Abstract
ASCL1 is one of the master transcription factors of small cell lung carcinoma (SCLC). To investigate the significance of ASCL1 in pulmonary neuroendocrine carcinoma, we performed 2 comparative RNA-seq studies between H69 (ASCL1-positive, classical type SCLC) and H69AR (ASCL1-negative, variant type SCLC) and between ASCL1-transfected A549 adenocarcinoma cell lines (A549(ASCL1+) cell lines) and A549(control) cell lines. RNA-seq analyses revealed that 940 genes were significantly different between the H69 and H69AR cell lines, and 728 between the A549(ASCL1+) and A549(control) cell lines. In total, 120 common genes between these analyses were selected as candidate ASCL1-related genes, and included genes with various cellular functions, such as neural development, secretion, growth, and morphology. Their expression degrees in three classical and two variant SCLC cell lines, two A549(ASCL1+) and two A549(control) cell lines were subjected to quantitative PCR analyses. Since the candidate ASCL1-related genes were strongly expressed in the classical SCLC and A549(ASCL1+) cell lines and more weakly expressed in the variant SCLC and A549(control) cell lines, the ASCL1-related 7 molecules INSM1, ISL1, SYT4, KCTD16, SEZ6, MS4A8, and COBL were further selected. These molecules suggested diverse functions for A549(ASCL1+): INSM1 and ISL1 are transcription factors associated with neuroendocrine differentiation, while SYT4, KTCD16, and SEZ6 may be related to neurosecretory functions and MS4A8 and COBL to cell growth and morphology. An immunohistochemistry of these seven molecules was performed on lung carcinoma tissues and the xenotransplanted tumors of A549(ASCL1+), and they were preferentially and positively stained in ASCL1-postive tumor tissues.

PMID: 32170367 [PubMed - as supplied by publisher]

Permalink for 'Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT).'

Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT).

Fetched: March 16th, 2020, 5:00am GMT

Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT).

J Nucl Med. 2020 Mar 13;:

Authors: Zhang J, Liu Q, Singh A, Schuchardt C, Kulkarni HR, Baum RP

Abstract
The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with 177Lu- and/or 90Y- DOTATOC/DOTATATE PRRT between 2/2002 and 7/2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT prior to treatment and were followed 3-189 months. Kaplan-Meier analysis, log-rank test (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: 199 patients (40.2%) presented with pancreatic NEN, 49 with CUP (cancer of unknown primary), 139 with midgut NEN, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8 and other locations in 42 patients. FDG-PET/CT was positive in 382 (77.2%) patients and 113 (22.8%) were FDG-negative before PRRT, while 100% were 68Ga-DOTATOC/TATE/NOC positive. For all patients, the median PFS and OS, defined from start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive FDG predicted shorter PFS (18.5 mo vs 24.1 mo; P = 0.0015) and OS (53.2 mo vs 83.1 mo; P < 0.001) than negative FDG. Amongst the pancreatic NEN, the median OS was 52.8 mo in FDG positive and 114.3 mo in FDG negative subjects (P = 0.0006). For all patients with positive 18F-FDG uptake, and a ratio of the highest SUVmax on 68Ga-SSTR PET to the most 18F-FDG-avid tumor lesions >2, the median OS was 53.0 mo, compared to 43.4 mo in those patients with a ratio <2 (P = 0.030). For patients with no 18F-FDG uptake (complete "mismatch" imaging pattern), the median OS was 108.3 mo vs 76.9 mo for SUVmax >15.0 and ≤15.0 on 68Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on 18F-FDG PET is an independent prognostic factor in patients with NEN treated with PRRT. Metabolic imaging with 18F-FDG PET/CT compliments the molecular imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative 18F-FDG PET/CT imaging is associated with the most favorable long-term prognosis.

PMID: 32169914 [PubMed - as supplied by publisher]

Permalink for 'Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: a Single-Center Retrospective Study.'

Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: a Single-Center Retrospective Study.

Fetched: March 16th, 2020, 5:00am GMT

Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: a Single-Center Retrospective Study.

J Nucl Med. 2020 Mar 13;:

Authors: Derlin T, Werner RA, Lafos M, Henkenberens C, von Klot CAJ, Sommerlath Sohns J, Ross TL, Bengel FM

Abstract
Introduction: Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer (mCRPC). We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of PSMA-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing 177Lu-PSMA-617 RLT. The primary endpoint was PSA response in relation to baseline neuroendocrine marker profiles. Additional endpoints included progression-free survival. Tumor uptake on post-therapeutic scans, a known predictive marker for response, was used as control-variable. Results: Neuroendocrine biomarker profiles were abnormal in the majority of patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict adverse outcome of RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving tumor-response.

PMID: 32169910 [PubMed - as supplied by publisher]

Genomic Subtyping in Bladder Cancer.

Fetched: March 15th, 2020, 5:01am GMT

Genomic Subtyping in Bladder Cancer.

Curr Urol Rep. 2020 Mar 13;21(2):9

Authors: Jalanko T, de Jong JJ, Gibb EA, Seiler R, Black PC

Abstract
PURPOSE OF REVIEW: Molecular characterization of cancer allows us to understand oncogenesis and clinicalÂ prognosis as well as facilitates development of biomarkers and treatment. Our aim was to review the current literature on genomic characterization of bladder cancer, and how far we are in implementing genomics into clinical practice.
RECENT FINDINGS: Bladder cancers are molecularly diverse tumors with a high mutational rate. On molecular level, bladder cancer can be categorized into at least six subtypes called luminal-papillary, luminal-unstable, luminal non-specified, basal-squamous, neuroendocrine-like, and stroma-rich. These subtypes have characteristic genomic and transcriptomic profiles and appear to have different prognoses. Several molecular subtypes have been identified in bladder cancer. Prospective trials are underway to validate the applicability of genomic subtypes for clinical decision making. Further integrative analyses of genomic alterations, gene expression, epigenetics, and proteomics need to be performed before genomic subtyping can be attained in clinical practice.

PMID: 32166460 [PubMed - in process]

Preliminary evaluation of GLP-1R PET in the diagnosis and risk stratification of pheochromocytomas.

Fetched: March 15th, 2020, 5:01am GMT

Preliminary evaluation of GLP-1R PET in the diagnosis and risk stratification of pheochromocytomas.

Neoplasma. 2020 Jan;67(1):27-36

Authors: Li M, Liu Y, Xu Y, Li Y, Pan D, Wang L, Yan J, Wang X, Yang R, Yang M

Abstract
Noninvasive imaging methods for the diagnosis and risk stratification of pheochromocytomas (PHEOs) remain a great clinical challenge. The glucagon-like peptide-1 receptor (GLP-1R) has been validated to be overexpressed in PHEOs and therefore may be a reliable target for PHEOs. In this study, we firstly synthesized a novel radiotracer 68Ga-NOTA-MAL-Cys39-exendin-4 that specifically targets GLP-1R and evaluated the performance of GLP-1R PET for the diagnosis and risk stratification of PHEOs. Cys39-exendin-4 was conjugated to NOTA-MAL and then radiolabeled with 68Ga. The reaction was completed within 20 min with a yield of 91.6 Â± 2.8%. In vitro cell uptake studies validated its high specificity. PET images showed promising tumor visualization with high uptake (1.88 Â± 0.10 %ID/g for PC-12 poorly differentiated tumors and 1.09 Â± 0.003 %ID/g for PC-12 highly differentiated tumors at 30min after injection). There was a significant difference in the uptake of 68Ga-NOTA-MAL-Cys39-exendin-4 between PC-12 poorly and highly differentiated tumors (p < 0.001), but no significant difference could be observed by 18F-FDG PET. Biodistribution results confirmed the findings of GLP-1R PET and demonstrated that 131I-MIBG couldn't be used for the risk stratification of PHEOs. Immunohistochemistry (IHC) staining revealed differences in GLP-1R expression between PC-12 poorly and highly differentiated tumor tissues. These results demonstrated that 68Ga-NOTA-MAL-Cys39-exendin-4 can specifically target GLP-1R with favorable pharmacokinetic properties. GLP-1R PET can be used for PHEOs detection and has potential for the risk stratification of PHEOs.

PMID: 31686522 [PubMed - indexed for MEDLINE]

Pseudomelanoma: Spontaneous Myopic Choroidal Hemorrhage.

Fetched: March 15th, 2020, 5:01am GMT

Pseudomelanoma: Spontaneous Myopic Choroidal Hemorrhage.

Ophthalmology. 2019 11;126(11):1491

Authors: Li J, Seider MI

PMID: 31635699 [PubMed - indexed for MEDLINE]

Endothelial Calcineurin Signaling Restrains Metastatic Outgrowth by Regulating Bmp2.

Fetched: March 15th, 2020, 5:01am GMT

Endothelial Calcineurin Signaling Restrains Metastatic Outgrowth by Regulating Bmp2.

Cell Rep. 2019 01 29;26(5):1227-1241.e6

Authors: Hendrikx S, Coso S, Prat-Luri B, Wetterwald L, Sabine A, Franco CA, Nassiri S, Zangger N, Gerhardt H, Delorenzi M, Petrova TV

Abstract
Calcineurin/NFAT signaling is active in endothelial cells and is proposed to be an essential component of the tumor angiogenic response. Here, we investigated the role of endothelial calcineurin signaling inÂ vivo in physiological and pathological angiogenesis and tumor metastasis. We show that this pathway is dispensable for retinal and tumor angiogenesis, but it is implicated in vessel stabilization. While ablation of endothelial calcineurin does not affect the progression of primary tumors or tumor cell extravasation, it does potentiate the outgrowth of lung metastases. We identify Bmp2 as a downstream target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. We reveal a dual role of calcineurin/NFAT signaling in vascular regression or stabilization and in the tissue-specific production of an angiocrine factor restraining cancer cell outgrowth. Our results suggest that, besides targeting the immune system, post-transplantation immunosuppressive therapy with calcineurin inhibitors directly targets the endothelium, contributing to aggressive cancer progression.

PMID: 30699351 [PubMed - indexed for MEDLINE]

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment.

Fetched: March 15th, 2020, 5:01am GMT

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment.

Cell Biol Toxicol. 2019 02;35(1):1-14

Authors: Marcell Szasz A, Malm J, Rezeli M, Sugihara Y, Betancourt LH, Rivas D, Gyorffy B, Marko-Varga G

Abstract
There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( [https:] ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period.

PMID: 30357519 [PubMed - indexed for MEDLINE]

Molecular Testing for Cutaneous Melanoma: An Update and Review.

Fetched: March 15th, 2020, 5:01am GMT

Molecular Testing for Cutaneous Melanoma: An Update and Review.

Arch Pathol Lab Med. 2019 07;143(7):811-820

Authors: Lee JJ, Lian CG

Abstract
CONTEXT.—: The steady rise in the incidence of cutaneous malignant melanoma and its inherently difficult-to-interpret histopathology continues to fuel an increasing demand for diagnostically and prognostically insightful adjunctive molecular tests among both clinicians and dermatopathologists. A number of DNA, RNA, and epigenetically based assays have now been developed and are at various stages of experimental and/or clinical use.
OBJECTIVE.—: To examine the evidence for the utility and limitations of these leading candidates for the diagnosis and risk stratification of melanoma and related melanocytic neoplasms.
DATA SOURCES.—: The available English medical literature was reviewed in the preparation of this manuscript.
CONCLUSIONS.—: Comparative genomic hybridization, fluorescence in situ hybridization, RNA-based gene expression profiling, and immunohistochemical assays for novel genetic and epigenetic markers will help bring diagnostic and prognostic accuracy to the assessment of melanocytic neoplasms.

PMID: 30354276 [PubMed - indexed for MEDLINE]

A Practical Approach to the Diagnosis of Melanocytic Lesions.

Fetched: March 15th, 2020, 5:01am GMT

A Practical Approach to the Diagnosis of Melanocytic Lesions.

Arch Pathol Lab Med. 2019 07;143(7):789-810

Authors: Harvey NT, Wood BA

Abstract
CONTEXT.—: Melanocytic lesions are common in routine surgical pathology. Although the majority of these lesions can be confidently diagnosed using well-established morphologic criteria, there is a significant subset of lesions that can be diagnostically difficult. These can be a source of anxiety for patients, clinicians, and pathologists, and the potential consequences of a missed diagnosis of melanoma are serious.
OBJECTIVE.—: To provide a practical approach to the diagnosis of melanocytic lesions, including classic problem areas as well as suggestions for common challenges and appropriate incorporation of ancillary molecular techniques.
DATA SOURCES.—: Literature search using PubMed and Google Scholar, incorporating numerous search terms relevant to the particular section, combined with contemporaneous texts and lessons from personal experience.
CONCLUSIONS.—: Although a subset of melanocytic lesions can be diagnostically challenging, the combination of a methodical approach to histologic assessment, knowledge of potential diagnostic pitfalls, opinions from trusted colleagues, and judicious use of ancillary techniques can help the pathologist navigate this difficult area.

PMID: 30059258 [PubMed - indexed for MEDLINE]

Prognostic role of lymphocyte-to-monocyte ratio in pancreatic neuroendocrine neoplasms.

Fetched: March 14th, 2020, 5:03am GMT

Prognostic role of lymphocyte-to-monocyte ratio in pancreatic neuroendocrine neoplasms.

Endocr Connect. 2020 Mar 01;:

Authors: Zhou W, Kuang T, Han X, Chen W, Xu X, Lou W, Wang D

Abstract
OBJECTIVES: Systemic inflammation markers have been demonstrated to be associated with prognosis in various tumors. In this study, we aimed to assess the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index and the counts of lymphocyte, monocyte and neutrophil in predicting prognosis among patients with resected pancreatic neuroendocrine neoplasms (pNENs).
METHODS: A total of 174 patients were included into study. Univariate and multivariate analyses were performed to evaluate the predictive roles of inflammation markers for relapse-free survival (RFS) and overall survival (OS) in pNEN patients.
RESULTS: The optimal cut-off values of NLR, LMR and lymphocyte count were 1.9, 5.0 and 1.4 ×109/L determined by the X-tile software. RFS was found to be significantly longer in patients with NLR ≤ 1.9 (P = 0.041), LMR > 5.0 (P < 0.001) and lymphocyte count > 1.4 ×109/L (P = 0.002) in comparison to those with NLR > 1.9, LMR ≤ 5.0 and lymphocyte count ≤ 1.4 ×109/L, respectively. Multivariate analysis revealed LMR (hazard ratio 0.30, 95% confidence interval 0.11-0.85, P = 0.023) was an independent predictor for RFS, but not NLR or lymphocyte count. For long-term survival analysis, patients with NLR ≤ 1.9 (P = 0.016) were found to be associated with favorable OS, but NLR was not an independent factor validated by multivariate analysis.
CONCLUSIONS: Preoperative LMR is an independent systemic inflammation marker to predict relapses in pNEN patients who underwent curative resections, whose clinical value needs to be verified in further large sample-based prospective studies.

PMID: 32163917 [PubMed - as supplied by publisher]

Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.

Fetched: March 14th, 2020, 5:03am GMT

Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.

Oncologist. 2020 Mar;25(3):259-265

Authors: Brighi N, Panzuto F, Modica R, Gelsomino F, Albertelli M, Pusceddu S, Massironi S, Lamberti G, Rinzivillo M, Faggiano A, Spallanzani A, Ferone D, Prinzi N, Rossi RE, Annibale B, Colao AM, Campana D

Abstract
BACKGROUND: Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs.
MATERIALS AND METHODS: A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start.
RESULTS: A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease.
CONCLUSION: We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned.
IMPLICATIONS FOR PRACTICE: The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.

PMID: 32162819 [PubMed - in process]

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

Fetched: March 14th, 2020, 5:03am GMT

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

J Vet Med Sci. 2020 Mar 12;:

Authors: Morita C, Tanaka M, Noguchi S, Shimamura S, Wada Y, Izawa T, Yamate J, Kuwamura M

Abstract
An 11-year-old female French Bulldog was presented with a mass at the base of the heart, detected by X-ray and echocardiography. Clinical abnormality included abdominal retention by ascites. Radiation therapy was performed for 5 weeks. The mass volume didn't change during the radiotherapy. The condition became worse and the dog died 6 months after the initial presentation and necropsy was performed. Grossly, the mass, 12.5×6.5×6.0 cm in size, was found at the base of the heart. Histopathological examination revealed that cardiac mass was composed of alveolar, bundle and diffuse proliferation of neoplastic cells. Most of the neoplastic cells showed a spindle morphology; in some areas small round or polyhedral neoplastic cells were observed. Occasional cartilage metaplasia was seen multifocal in the mass, and it was surrounded by the sarcomatoid proliferation. Electron microscopy revealed a few neuroendocrine granules in the cytoplasm of spindle and polyhedral neoplastic cells. Metastatic cells in the lungs which had not irradiated demonstrated typical morphology of aortic body tumors. Based on these findings, the case was diagnosed as an aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia.

PMID: 32161252 [PubMed - as supplied by publisher]

Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors.

Fetched: March 14th, 2020, 5:03am GMT

Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors.

Sci Transl Med. 2020 Mar 11;12(534):

Authors: Schafer JM, Lehmann BD, Gonzalez-Ericsson PI, Marshall CB, Beeler JS, Redman LN, Jin H, Sanchez V, Stubbs MC, Scherle P, Johnson KN, Sheng Q, Roland JT, Bauer JA, Shyr Y, Chakravarthy B, Mobley BC, Hiebert SW, Balko JM, Sanders ME, Liu PCC, Pietenpol JA

Abstract
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to endocrine therapy or human epidermal growth factor receptor 2 (HER2)-targeted therapies. Individuals with TNBC experience higher rates of relapse and shorter overall survival compared to patients with receptor-positive breast cancer subtypes. Preclinical discoveries are needed to identify, develop, and advance new drug targets to improve outcomes for patients with TNBC. Here, we report that MYCN, an oncogene typically overexpressed in tumors of the nervous system or with neuroendocrine features, is heterogeneously expressed within a substantial fraction of primary and recurrent TNBC and is expressed in an even higher fraction of TNBCs that do not display a pathological complete response after neoadjuvant chemotherapy. We performed high-throughput chemical screens on TNBC cell lines with varying amounts of MYCN expression and determined that cells with higher expression of MYCN were more sensitive to bromodomain and extraterminal motif (BET) inhibitors. Combined BET and MEK inhibition resulted in a synergistic decrease in viability, both in vitro and in vivo, using cell lines and patient-derived xenograft (PDX) models. Our preclinical data provide a rationale to advance a combination of BET and MEK inhibitors to clinical investigation for patients with advanced MYCN-expressing TNBC.

PMID: 32161105 [PubMed - in process]

Permalink for 'Recurrent Catecholamine-Induced Cardiomyopathy and Hypertensive Emergencies: A presentation of Pheochromocytoma and Related Concerns.'

Recurrent Catecholamine-Induced Cardiomyopathy and Hypertensive Emergencies: A presentation of Pheochromocytoma and Related Concerns.

Fetched: March 14th, 2020, 5:03am GMT

Recurrent Catecholamine-Induced Cardiomyopathy and Hypertensive Emergencies: A presentation of Pheochromocytoma and Related Concerns.

S D Med. 2020 Feb;73(2):78-80

Authors: Sethi P, Chang GV, Gowda SN, Elnair R, Fenner R, Lamfers R

Abstract
Catecholamine-induced cardiomyopathy (CIC) and pheochromocytoma are both rare entities, and their exact incidence and prevalence are unknown. Pheochromocytoma has been implicated as one of the causes of CIC or Takotsubo syndrome (TTS) by means of case reports and retrospective reviews. However, the evaluation of any patient with TTS and pheochromocytoma is often faced with multiple challenges due to its rarity and atypical presentations, which subsequently leads to delay in diagnosis. Here, we present a case of a 51-year old female who had three distinct episodes of TTS and now presented in a hypertensive emergency with angina, palpitations, headache, nausea, and vomiting. She was treated for non-ST elevation myocardial infarction (NSTEMI) but coronary angiogram revealed patent coronary arteries. Due to the paroxysmal nature of her hypertensive emergencies and variable blood pressure response, pheochromocytoma was suspected. On further evaluation, she was found to have elevated metanephrines and a 6.3 cm left adrenal mass on CT scan. This case emphasizes the importance of considering or identifying pheochromocytoma as an underlying primary etiology for recurrent episodes of TTS and related concerns such as choice of anti-hypertensive agents.

PMID: 32135056 [PubMed - indexed for MEDLINE]

Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo.

Fetched: March 14th, 2020, 5:03am GMT

Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo.

Photochem Photobiol Sci. 2020 Feb 19;19(2):171-179

Authors: Malesu R, Martin AJ, Lyons JG, Scolyer RA, Chen AC, McKenzie CA, Madore J, Halliday GM, Damian DL

Abstract
Nicotinamide (NAM), an amide form of vitamin B3, replenishes cellular energy after ultraviolet radiation (UVR) exposure, thereby enhancing DNA repair and reducing UVR's immunosuppressive effects. NAM reduces actinic keratoses and new keratinocyte cancers in high risk individuals, but its effects on melanoma are unknown. Melanomas arising on NAM or placebo within the ONTRAC skin cancer chemoprevention trial (Oral Nicotinamide To Reduce Actinic Cancer) were examined by immunohistochemistry. The effects of NAM (50 μM, 5 mM and 20 mM) on the viability, proliferation and invasiveness of four human melanoma cell lines and on the viability and proliferation of two human melanocyte lines, with and without UV irradiation were also investigated. 50 μM NAM did not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, whereas concentrations too high to be achievable in vivo reduced viability and proliferation. Nicotinamide did not enhance melanoma viability, proliferation or invasiveness in vitro, providing additional confidence in its safety for use in clinical trials in high risk patients. Peritumoral and tumour infiltrating CD4+ and CD8+ lymphocytes were significantly increased in melanomas arising on NAM compared to those arising on placebo. Given the chemopreventive activity of nicotinamide against keratinocyte cancers, its DNA repair enhancing effects in melanocytes and now its potential enhancement of tumour-infiltrating lymphocytes and lack of adverse effects on melanoma cell growth and proliferation, clinical trials of nicotinamide for melanoma chemoprevention are now indicated.

PMID: 31942903 [PubMed - indexed for MEDLINE]

Calcitonin-negative medullary thyroid carcinoma: the 'triple-negative' phenotype.

Fetched: March 14th, 2020, 5:03am GMT

Calcitonin-negative medullary thyroid carcinoma: the 'triple-negative' phenotype.

Ann R Coll Surg Engl. 2020 Mar;102(3):e63-e66

Authors: Murphy DC, Johnson SJ, Aspinall S

Abstract
Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterised by classic medullary thyroid carcinoma morphology without raised serum calcitonin. A 24-year-old woman presented with a slow-growing, right-sided neck swelling. She underwent an ultrasound scan, cytopathological and histopathological examination, and tests for alternative diagnoses. The ultrasound showed a heterogeneous, hyperechoic nodule in the right thyroid lobe. Serum calcitonin was normal. Cytopathology and histopathology showed typical medullary thyroid carcinoma morphology but without calcitonin upon immunostaining and mRNA in situ hybridisation. A 'triple-negative' calcitonin-negative medullary thyroid carcinoma was diagnosed. A completion thyroidectomy with bilateral central lymph node dissection was performed. The patient remains well three-years post-surgery. When cytopathology suggests a medullary thyroid carcinoma, serum calcitonin, pro-calcitonin, carcinoembryonic antigen and calcitonin-gene-related peptide should be measured to identify cases of calcitonin-negative medullary thyroid carcinoma. They should also be measured post-treatment for monitoring purposes. This will aid future calcitonin-negative medullary thyroid carcinoma diagnoses and will inform prognostic stratification and influence treatment decisions.

PMID: 31841033 [PubMed - indexed for MEDLINE]

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (464 unread)

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