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Acinic Cell Carcinoma - News-Medical.net

Posted: June 20th, 2018, 11:23pm GMT

Acinic Cell Carcinoma
News-Medical.net
Acinic cell carcinoma is a rare cancer of the salivary glands that originates from the parotid gland. It is a low-grade salivary neoplasm that constitutes about 5% to 17% of cases involving salivary gland malignancies. In comparison with other salivary ...

Genomic analyses identify molecular subtypes of pancreatic cancer - Nature.com

Posted: February 24th, 2016, 3:52pm GMT

Genomic analyses identify molecular subtypes of pancreatic cancer
Nature.com
These 4 subtypes were associated with specific histological characteristics: (1) squamous with adenosquamous carcinomas (6/25 in squamous versus 1/71 in the rest, P = 0.0011 Fisher's exact test); (2) pancreatic progenitor and (3) immunogenic with ...

Pathophysiological role of microRNA-29 in pancreatic cancer stroma - Nature.com

Posted: June 22nd, 2015, 9:07am GMT

Nature.com

Pathophysiological role of microRNA-29 in pancreatic cancer stroma
Nature.com
A growing body of evidence suggests that pancreatic stellate cells (PSCs) are the major stromal cells responsible for fibrotic stroma. In normal pancreas, PSCs are located in periacinar spaces and remain quiescent. In response to pancreatic injury or ...

Decreased LKB1 predicts poor prognosis in Pancreatic Ductal Adenocarcinoma - Nature.com

Posted: May 27th, 2015, 8:15am GMT

Nature.com

Decreased LKB1 predicts poor prognosis in Pancreatic Ductal Adenocarcinoma
Nature.com
Analysis of LKB1 mutations and other molecular alterations in pancreatic acinar cell carcinoma . Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24, 1229–1236, doi:10.1038/modpathol.2011.83 (2011).

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression.

Fetched: June 15th, 2018, 5:00am GMT

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression.

Cell Rep. 2017 Oct 24;21(4):966-978

Authors: Ferreira RMM, Sancho R, Messal HA, Nye E, Spencer-Dene B, Stone RK, Stamp G, Rosewell I, Quaglia A, Behrens A

Abstract
The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

PMID: 29069604 [PubMed - indexed for MEDLINE]

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.

Fetched: June 15th, 2018, 5:00am GMT

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.

Cell Signal. 2017 Dec;40:91-98

Authors: Datta A, Sandilands E, Mostov KE, Bryant DM

Abstract
The formation of lumens in epithelial tissues requires apical-basal polarization of cells, and the co-ordination of this individual polarity collectively around a contiguous lumen. Signals from the Extracellular Matrix (ECM) instruct epithelia as to the orientation of where basal, and thus consequently apical, surfaces should be formed. We report that this pathway is normally absent in Calu-3 human lung adenocarcinoma cells in 3-Dimensional culture, but that paracrine signals from MRC5 lung fibroblasts can induce correct orientation of polarity and acinar morphogenesis. We identify HGF, acting through the c-Met receptor, as the key polarity-inducing morphogen, which acts to activate β1-integrin-dependent adhesion. HGF and ECM-derived integrin signals co-operate via a c-Src-dependent inhibition of the RhoA-ROCK1 signalling pathway via p190A RhoGAP. This occurred via controlling localization of these signalling pathways to the ECM-abutting surface of cells in 3-Dimensional culture. Thus, stromal derived signals can influence morphogenesis in epithelial cells by controlling activation and localization of cell polarity pathways.

PMID: 28888686 [PubMed - indexed for MEDLINE]

Aging dependent effect of nuclear tau.

Fetched: June 13th, 2018, 5:00am GMT

Aging dependent effect of nuclear tau.

Brain Res. 2017 Dec 15;1677:129-137

Authors: Gil L, Federico C, Pinedo F, Bruno F, Rebolledo AB, Montoya JJ, Olazabal IM, Ferrer I, Saccone S

Abstract
Tau protein is characterized by a complex pattern of phosphorylation and is localized in the cytoplasm and nucleus in both neuronal and non-neuronal cells. Human AT100 nuclear tau, endowed by phosphorylation in Thr212/Ser214, was recently shown to decline in cornus ammonis 1 (CA1) and dentate gyrus (DG) in Alzheimer's disease (AD), but a defined function for this nuclear tau remains unclear. Here we show that AT100 progressively increases in the nuclei of neuronal and non-neuronal cells during aging, and decreases in the more severe AD stages, as recently shown, and in cancer cells (colorectal adenocarcinoma and breast cancer). AT100, in addition to a co-localization with the DAPI-positive heterochromatin, was detected in the nucleolus of pyramidal cells from the CA1 region, shown to be at its highest level in the more senescent cells and in the first stage of AD (ADI), and disappearing in the more severe AD cases (ADIV). Taking into account the nuclear distribution of AT100 during cell aging and its relation to the chromatin changes observed in degenerated neurons, as well as in cancerous cells, which are both cellular pathologies associated with age, we can consider the Thr212/Ser214 phosphorylated nuclear tau as a molecular marker of cell aging.

PMID: 28974363 [PubMed - indexed for MEDLINE]

Bioengineered Submucosal Organoids for In Vitro Modeling of Colorectal Cancer.

Fetched: June 13th, 2018, 5:00am GMT

Bioengineered Submucosal Organoids for In Vitro Modeling of Colorectal Cancer.

Tissue Eng Part A. 2017 Oct;23(19-20):1026-1041

Authors: Devarasetty M, Skardal A, Cowdrick K, Marini F, Soker S

Abstract
The physical nature of the tumor microenvironment significantly impacts tumor growth, invasion, and response to drugs. Most in vitro tumor models are designed to study the effects of extracellular matrix (ECM) stiffness on tumor cells, while not addressing the effects of ECM's specific topography. In this study, we bioengineered submucosal organoids, using primary smooth muscle cells embedded in collagen I hydrogel, which produce aligned and parallel fiber topography similar to those found in vivo. The fiber organization in the submucosal organoids induced an epithelial phenotype in spheroids of colorectal carcinoma cells (HCT-116), which were embedded within the organoids. Conversely, unorganized fibers drove a mesenchymal phenotype in the tumor cells. HCT-116 cells in organoids with aligned fibers showed no WNT signaling activation, and conversely, WNT signaling activation was observed in organoids with disrupted fibers. Consequently, HCT-116 cells in the aligned condition exhibited decreased cellular proliferation and reduced sensitivity to 5-fluorouracil chemotherapeutic treatment compared to cells in the unorganized construct. Collectively, the results establish a unique colorectal tumor organoid model to study the effects of stromal topography on cancer cell phenotype, proliferation, and ultimately, chemotherapeutic susceptibility. In the future, such organoids can utilize patient-derived cells for precision medicine applications.

PMID: 28922975 [PubMed - indexed for MEDLINE]

Permalink for 'Mucinous adenocarcinoma of prostate and prostatic adenocarcinoma with mucinous components: a clinicopathological analysis of 143 cases.'

Mucinous adenocarcinoma of prostate and prostatic adenocarcinoma with mucinous components: a clinicopathological analysis of 143 cases.

Fetched: June 13th, 2018, 5:00am GMT

Mucinous adenocarcinoma of prostate and prostatic adenocarcinoma with mucinous components: a clinicopathological analysis of 143 cases.

Histopathology. 2017 Oct;71(4):641-647

Authors: Samaratunga H, Delahunt B, Srigley JR, Yaxley J, Johannsen S, Coughlin G, Gianduzzo T, Kua B, Patterson I, Nacey JN, Egevad L

Abstract
AIM: The clinical significance of mucinous prostatic adenocarcinoma (PCa) remains uncertain.
METHODS: From 6440 cases of PCa treated by radical prostatectomy from 2009 to 2014, mucinous components of 5-100% were found in 143 (2.2%) cases.
RESULTS: The mean age was 61.4 years, mean pre-operative serum prostate-specific antigen (PSA) was 7.8 ng/ml and clinical stage category was cT1 in 81% and cT2 in 19% of cases. Cases were graded using the 2014 International Society of Urological Pathology recommendation of grading underlying architecture, and Gleason scores (GS) were 3 + 4 in 13.3%, 4 + 3 in 54.5%, 4 + 4 in 2.1%, 3 + 4 or 4 + 3 with tertiary 5 in 11.9% and 9-10 in 18.2%. The mucinous component invariably had a high-grade component. Extraprostatic extension was found in 46.8% of cases. In 21.6%, tumour volume was ≥3 cm³ and 9.7% had surgical margin positivity. Seminal vesicle involvement was found in 6.9%. In 73 cases the mucinous component was >25%, and when cases were divided on the basis of the area of mucin present (≤25 versus >25%) there was no significant difference between clinical or pathological features. Similar findings were achieved when cases were compared with grade-matched non-mucinous carcinoma controls. The 5-year biochemical recurrence rates for mucinous versus non-mucinous cancer were 12.5 versus 17% (P = 0.15).
CONCLUSION: PCa with mucinous components is often high grade; however, the prognosis appears to be similar to non-mucinous cancers of similar GS.

PMID: 28590015 [PubMed - indexed for MEDLINE]

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate.

Fetched: June 11th, 2018, 5:00am GMT

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate.

Hum Pathol. 2018 Jun 06;:

Authors: Xue W, Xin Z, Zhang Y, Jiang Z, Zhao L, Fan L, Wang Y, Xie S, Shangguan X, Zhu Y, Pan J, Liu Q, Huang Y, Dong B

Abstract
The correct diagnosis of small cell carcinoma (SCC) of the prostate is critical because of its aggressive behavior and poor prognosis. The histopathologic diagnosis could be challenging without neuroendocrine markers, which currently has limitations. Insulinomaassociated protein 1 (INSM1), a zinc-finger transcription factor, is considered to play an important role in the development of several neuroendocrine precursor cells. Its diagnosis value has only recently been evaluated. In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and nonneuroendocrine prostate tissues. To validate its possible utility as a diagnostic marker, the performance of chromogranin and synaptophysin was used for comparison. We found INSM1 mRNA is upregulated in neuroendocrine prostate carcinoma samples from the published data sets. The results were verified by the immunohistochemistry performance. INSM1 was positive in 92.3% of prostatic SCCs, compared with 53.8% positive for chromogranin, and 84.6% positive for synaptophysin. INSM1 was also stained all of the mixed SCC-acinar adenocarcinomas and metastatic SCCs progression from acinar adenocarcinoma. Only 3.4% of benign prostate tissues and 4.0% of prostate adenocarcinomas were INSM1 positive. Our data suggest that INSM1 is a novel sensitive and specific marker for detection of SCC of the prostate. Application of INSM1 in clinical pathologic diagnosis will be valuable.

PMID: 29885405 [PubMed - as supplied by publisher]

Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

Fetched: June 8th, 2018, 5:00am GMT

Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

J Gastrointest Surg. 2017 Dec;21(12):2132-2134

Authors: Dogeas E, Peng L, Choti MA

Abstract
Hepatoid adenocarcinoma is a rare type of extrahepatic cancer characterized by hepatocellular carcinoma-like histology. We present a case of a large solitary mass in the peripancreatic region found to be an isolated lymph node metastasis from an unknown primary hepatoid adenocarcinoma masquerading as an acinar carcinoma of the pancreas.

PMID: 28681213 [PubMed - indexed for MEDLINE]

Permalink for 'Clinical characteristics and prognosis of patients with lung adenosquamous carcinoma after surgical resection: results from two institutes.'

Clinical characteristics and prognosis of patients with lung adenosquamous carcinoma after surgical resection: results from two institutes.

Fetched: June 2nd, 2018, 5:00am GMT

Clinical characteristics and prognosis of patients with lung adenosquamous carcinoma after surgical resection: results from two institutes.

J Thorac Dis. 2018 Apr;10(4):2397-2402

Authors: Zhu L, Jiang L, Yang J, Gu W, He J

Abstract
Background: Adenosquamous carcinoma (ASC) is a mixed glandular and squamous cell carcinoma (SCC) with more aggressive behavior than the other histologic subtypes of lung cancer. We aim to evaluate the prognosis of patients with ASC after surgical resection.
Methods: We reviewed records of patients who underwent surgical resection for lung cancer in two institutes between January 2010 and December 2015. Survival data were collected with a median follow-up of 59 (range from 10 to 85) months. Kaplan-Meier survival curve was determined for all patients.
Results: Patients with ASC accounted for 1.6% of all NSCLC patients (33 males, 25 females). The cumulative postoperative 3- and 5-year survival rates were 56% and 48%, respectively. Overall survival (OS) was significantly lower in ASC patients than in adenocarcinoma (AC) patients operated during the same period (P<0.01). Patients with ASC containing acinar predominant AC had better survival than those with non-acinar predominant ASC (P=0.03). No difference of OS was found in patients with or without visceral pleural invasion (VPI), vascular invasion (VI) or EGFR mutation status. Multivariate analysis showed gender, pathological subtype, and TNM staging to be independent prognostic factors.
Conclusions: We demonstrated that ASC were uncommon and aggressive lung tumors. Predominant histological subtype of AC might be an independent prognostic factor for ASC. Further prospective studies are warranted to clarify the characteristics of this rare tumor.

PMID: 29850145 [PubMed]

Accuracy of preoperative fine needle aspiration in diagnosis of malignant parotid tumors.

Fetched: June 1st, 2018, 5:00am GMT

Accuracy of preoperative fine needle aspiration in diagnosis of malignant parotid tumors.

Saudi Med J. 2017 Oct;38(10):1000-1006

Authors: Marzouki HZ, Altabsh MA, Albakrei MO, Al-Khatib TA, Merdad MA, Farsi NJ

Abstract
OBJECTIVES: To determine the diagnostic accuracy of fine needle aspiration (FNA) for detecting malignant parotid tumors. Methods: We conducted a retrospective study of all patients diagnosed with benign or malignant parotid gland tumors in King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between January 2004 and May 2015. The records of 65 subjects were obtained. Histopathological findings and data from FNA examinations were obtained from medical records. Twenty-three subjects were excluded due to missing FNA, histopathology results or both. The sensitivity, specificity, negative predictive value, and positive predictive value of FNA for detecting malignant lesions were estimated and compared with the gold standard, histopathology. Results: The specimens of 5 cases were insufficient for diagnosis; therefore, 38 cases were diagnosed by FNA and had histopathological reports. Three cases were diagnosed positive for cancer using histopathology and missed by FNA, 3 were diagnosed as malignant lesions using both FNA and histopathology, and 32 cases were determined benign based on histopathology and FNA analysis. The total prevalence of parotid malignancies was 15.8%. The sensitivity of FNA for detecting malignancy was 50%, and the specificity was 100%; with a positive predictive value of 100% and negative predictive value of 91.4%. Conclusion: Fine needle aspiration is a highly specific, but only moderately sensitive test. We support the use of this method as an initial tool for diagnosing parotid gland malignancies, as it is a safe, rapid, and painless procedure, compared to histopathology.

PMID: 28917063 [PubMed - indexed for MEDLINE]

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.

Fetched: May 31st, 2018, 5:00am GMT

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.

Oncol Lett. 2018 Jun;15(6):8973-8982

Authors: Li C, Zheng X, Han Y, Lv Y, Lan F, Zhao J

Abstract
The present study assessed the effects of the tankyrase (TNKS) small molecule inhibitor XAV939 on the proliferation and migration of lung adenocarcinoma A549 cells and the possible underlying mechanism. To do this, the association between TNKS and the WNT/β-catenin signaling pathway in lung acinar adenocarcinoma was investigated. Immunohistochemistry was performed, which demonstrated that TNKS, β-catenin and Myc proto-oncogene protein (c-Myc) proteins are positively expressed in lung adenocarcinoma tissue; this expression was significantly higher than that in normal adjacent non-carcinoma tissues. A549 cell proliferation was inhibited in all XAV939-intervention groups examined. In the wound-healing assay, cells treated with different concentrations of XAV939 exhibited a significantly increased scratch width compared with the control group. Reverse transcription-semi-quantitative polymerase chain reaction analysis revealed that β-catenin mRNA expression was significantly decreased in A549 cells in response to different XAV939 concentrations compared with the control group. Immunofluorescence revealed that β-catenin protein, initially localized in the nucleus/cytoplasm, gradually translocated to the cytoplasm/membrane, an effect that was associated with increased drug concentration. TNKS, β-catenin and c-Myc protein expression in A549 cells treated with XAV939 was reduced compared with that in untreated cells. Therefore, abnormally high TNKS expression may promote the occurrence of lung cancer. The TNKS inhibitor XAV939 inhibited lung adenocarcinoma A549 cell proliferation and migration in vitro. The underlying mechanism by which XAV939 exerted its inhibitory effects may be associated with attenuation of the WNT signaling pathway.

PMID: 29805633 [PubMed]

Permalink for 'Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.'

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Fetched: May 25th, 2018, 5:00am GMT

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Mod Pathol. 2018 May 21;:

Authors: Suzuki M, Nakatani Y, Ito H, Narimatsu H, Yamada K, Yoshioka E, Washimi K, Okubo Y, Kawachi K, Miyagi Y, Yokose T

Abstract
Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for α-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type-nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary-predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P < 0.001). Univariate and multivariate analyses showed that adenocarcinomas with the fetal-type component had a significantly lower overall survival rate than the other histological subtypes, except for the micropapillary-predominant subtype. Our study demonstrated that adenocarcinomas with the fetal-type component had a poor prognosis that was comparable to that of micropapillary adenocarcinoma. The presence of the high-grade fetal adenocarcinoma component in lung adenocarcinomas is an important prognostic marker.

PMID: 29785018 [PubMed - as supplied by publisher]

[Acquired cystic kidney disease-associated renal cell carcinoma: a clinicopathologic study of three cases].

Fetched: May 25th, 2018, 5:00am GMT

[Acquired cystic kidney disease-associated renal cell carcinoma: a clinicopathologic study of three cases].

Zhonghua Bing Li Xue Za Zhi. 2018 May 08;47(5):366-371

Authors: Zhang W, Xu LL, Yu WJ, Wang Q, Jiang YX, Liu Y, Li YJ

Abstract
Objective: To study the clinicopathologic, immunohistochemical (IHC), histogenetic and prognostic features of acquired cystic kidney disease-associated renal cell carcinoma (ACKD-RCC). Methods: Three cases of ACKD-RCC, including two from 401 Hospital of PLA and one from the Affiliated Hospital of Qingdao University were studied by clinical, histological and IHC analysis with review of relevant literature. Results: All the three patients were male, ranging from 46 to 78 years old. All patients had history of chronic renal failure; two patients were treated with hemodialysis for 9 years and 11 years, respectively. In two cases the tumor sizes were 2.5 cm and 3.5 cm, respectively, and the tumor border was distinct. The remaining case showed extensive renal hemorrhage with an inconspicuous mass. Microscopically, the tumor cells were arranged in cribriform, microcystic or acinar structures, with variable papillary structure in one case. Hemorrhage of varying degrees was seen in all three cases, and obvious necrosis was noted in two. The tumor cells had deeply eosinophilic cytoplasm, indistinct cell border, round or oval nuclei, and prominent nucleoli (WHO/ISUP grade 3). Mitoses were rare. Abundant oxalate crystals were seen in two cases. The renal mesenchyme of all three cases were atrophic with variable cystic changes of the renal tubules, the lining cells showed atypical hyperplasia. IHC staining showed all tumors were diffusely positive for vimentin, CD10, RCC, CAM5.2, P504s and mitochondria in the cytoplasm, and were variably positive for EMA (2/3), CK7 (1/3), CA9 (1/3) and PAX8 (3/3). All cases were negative for CD117, HMB45, Melan A and TFE3. After 3-14 months follow-up, one patient died from renal failure six months after surgery. The other two patients were alive without tumor recurrence or metastasis. Conclusions: ACKD-RCC is a very rare renal cell carcinoma. The specific cribriform structure, deeply eosinophilic cytoplasm, prominent nucleoli (WHO/ISUP grade 3), and oxalate crystals deposition, associated with the history of ACKD could aid the diagnosis. ACKD-RCC arises from the proximal renal tubule and its histogenesis might be associated with proliferation and malignant change of the atypical epithelial cells of the cystic renal tubules. ACKD-RCC may have a favorable prognosis except for tumors with sarcomatoid differentiation.

PMID: 29783804 [PubMed - in process]

Permalink for 'Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles.'

Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles.

Fetched: May 25th, 2018, 5:00am GMT

Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles.

Int J Oncol. 2017 Oct;51(4):1035-1044

Authors: Mattheolabakis G, Wang R, Rigas B, Mackenzie GG

Abstract
Pancreatic cancer (PC) is one of the most difficult cancers to treat. Since the current chemotherapy is inadequate and various biological approaches have failed, the need for agents that have a potential to treat PC is pressing. Phospho-valproic acid (P-V), a novel anticancer agent, is efficacious in xenograft models of human PC and is apparently safe. In the present study, we evaluated whether formulating P-V in nanoparticles could enhance its anticancer efficacy. In a mouse model of Kras/pancreatitis-associated PC, P-V, orally administered, inhibited the incidence of acinar-to-ductal metaplasia by 60%. To improve its efficacy, we formulated P-V in five different polymeric nanoparticles. Poly-(L)-lactic acid- poly(ethylene glycol) (PLLA-PEG) nanoparticles proved the optimal formulation. PLLA-PEG improved P-V's pharmacokinetics in mice enhancing the levels of P-V in blood. Compared to control, P-V formulated in PLLA-PEG suppressed the growth of MIA PaCa-2 xenografts by 81%, whereas P-V alone reduced it by 51% (p<0.01). Furthermore, P-V formulated in PLLA-PEG inhibited acinar-to-ductal metaplasia in mice with activated Kras, reducing it by 87% (p<0.02). In both disease models, P-V suppressed STAT3 phosphorylation at the Ser727 and Tyr705 residues; STAT3 is the pivotal molecular target of P-V. In conclusion, P-V is a promising agent against PC, and its formulation in PLLA-PEG nanoparticles enhances its efficacy by improving its pharmacokinetics.

PMID: 28849098 [PubMed - indexed for MEDLINE]

Molecular Diagnostics in the Neoplasms of the Pancreas, Liver, Gallbladder, and Extrahepatic Biliary Tract: 2018 Update.

Fetched: May 21st, 2018, 5:00am GMT

Molecular Diagnostics in the Neoplasms of the Pancreas, Liver, Gallbladder, and Extrahepatic Biliary Tract: 2018 Update.

Clin Lab Med. 2018 Jun;38(2):367-384

Authors: Zhang L, Bluth MH, Bhalla A

Abstract
Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations.

PMID: 29776636 [PubMed - in process]

Permalink for 'GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.'

GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.

Fetched: May 17th, 2018, 5:00am GMT

GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.

Proc Natl Acad Sci U S A. 2017 05 16;114(20):E4020-E4029

Authors: Shen J, Ha DP, Zhu G, Rangel DF, Kobielak A, Gill PS, Groshen S, Dubeau L, Lee AS

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease in critical need of new therapeutic strategies. Here, we report that the stress-inducible 78-kDa glucose-regulated protein (GRP78/HSPA5), a key regulator of endoplasmic reticulum homeostasis and PI3K/AKT signaling, is overexpressed in the acini and PDAC of Pdx1-Cre;KrasG12D/+;p53f/+ (PKC) mice as early as 2 mo, suggesting that GRP78 could exert a protective effect on acinar cells under stress, as during PDAC development. The PKC pancreata bearing wild-type Grp78 showed detectable PDAC by 3 mo and rapid subsequent tumor growth. In contrast, the PKC pancreata bearing a Grp78f/+ allele (PKC78f/+ mice) expressing about 50% of GRP78 maintained normal sizes during the early months, with reduced proliferation and suppression of AKT, S6, ERK, and STAT3 activation. Acinar-to-ductal metaplasia (ADM) has been identified as a key tumor initiation mechanism of PDAC. Compared with PKC, the PKC78f/+ pancreata showed substantial reduction of ADM as well as pancreatic intraepithelial neoplasia-1 (PanIN-1), PanIN-2, and PanIN-3 and delayed onset of PDAC. ADM in response to transforming growth factor α was also suppressed in ex vivo cultures of acinar cell clusters isolated from mouse pancreas bearing targeted heterozygous knockout of Grp78 (c78f/+ ) and subjected to 3D culture in collagen. We further discovered that GRP78 haploinsufficiency in both the PKC78f/+ and c78f/+ pancreata leads to reduction of epidermal growth factor receptor, which is critical for ADM initiation. Collectively, our studies establish a role for GRP78 in ADM and PDAC development.

PMID: 28461470 [PubMed - indexed for MEDLINE]

The screening and electron microscopy observation of mammary analogue secretory carcinoma in Chinese.

Fetched: May 14th, 2018, 5:00am GMT

The screening and electron microscopy observation of mammary analogue secretory carcinoma in Chinese.

J Craniomaxillofac Surg. 2017 Oct 19;:

Authors: Zhong Y, Liu L, Qi B, Song X, Shen L, Li H

Abstract
Mammary analogue secretory carcinoma of salivary gland (MASC) is a tumor with histopathologic and immunophenotypic features mimicking secretory carcinoma of the breast harboring the ETV6 split. The expression of mammaglobin, S-100, Ki-67, P63 and ETV6 split were detected in twelve cases of acinar cell carcinoma and fourteen cases of mammary analogue secretory carcinoma of salivary gland by immunohistochemistry and fluorescence in situ hybridization respectively. The expression of ETV6 gene split was detected in fourteen mammary analogue secretory carcinomas of salivary gland with positive expression of mammaglobin. Eight of mammary analogue secretory carcinomas of salivary gland also tested positive for the ETV6 gene split via fluorescence in-situ hybridization (FISH). The concordance rate of the immunohistochemistry and FISH was 72.3%. Mammaglobin and ETV6 gene split detection could help to distinguish mammary analogue secretory carcinoma of salivary gland. The mammary analogue secretory carcinoma of salivary gland specimens were also examined under transmission electron microscope. And apical junctional complexes were observed in the loosely connected tumor cells.

PMID: 29752049 [PubMed - as supplied by publisher]

Central Acinic Cell Carcinoma of the Mandible Simulating as Benign Odontogenic Lesion: A Case Report.

Fetched: May 13th, 2018, 5:00am GMT

Central Acinic Cell Carcinoma of the Mandible Simulating as Benign Odontogenic Lesion: A Case Report.

Iran J Med Sci. 2018 Mar;43(2):223-226

Authors: Bajpai M, Pardhe N, Chandolia B, Arora M

Abstract
Centrally occurring salivary gland tumors are rare. Because of a considerable overlap between the clinical and histopathological features, this group of tumors often produces a diagnostic difficulty to the clinicians and oral pathologists. Acinic cell carcinoma (ACC) is an unusual, low-grade, malignant salivary gland tumor that represents approximately 2% of the salivary gland tumors with almost 90% arising in the parotid gland. The rest involve the submandibular and the minor salivary gland. ACC of the jaw is extremely rare and, to our knowledge, only 8 cases have been reported in the English literature. Herein, a case of primary intraosseous ACC of the mandible in a 31-year-old woman is presented. The present case is unique, as the central ACC has never been reported in a patient in the third decade of life. The complete surgical removal of the tumor was carried out under general anesthesia along with the extraction of teeth #31, #32, #41, and #42. The follow-up period of 1-year was uneventful.

PMID: 29749993 [PubMed]

Permalink for 'Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.'

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

Fetched: May 11th, 2018, 5:00am GMT

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

Gastroenterology. 2018 04;154(5):1494-1508.e13

Authors: He P, Yang JW, Yang VW, Bialkowska AB

Abstract
BACKGROUND & AIMS: Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar-to-ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs.
METHODS: We performed studies in adult mice with conditional disruption of Klf5 (Klf5fl/fl) and/or expression of KrasG12D (LSL-KrasG12D) via CreERTM recombinase regulated by an acinar cell-specific promoter (Ptf1a). Activation of KrasG12D and loss of KLF5 was achieved by administration of tamoxifen. Pancreatitis was induced in mice by administration of cerulein; pancreatic tissues were collected, analyzed by histology and immunohistochemistry, and transcriptomes were compared between mice that did or did not express KLF5. We performed immunohistochemical analyses of human tissue microarrays, comparing levels of KLF5 among 96 human samples of PDAC. UN-KC-6141 cells (pancreatic cancer cells derived from Pdx1-Cre;LSL-KrasG12D mice) were incubated with inhibitors of different kinases and analyzed in proliferation assays and by immunoblots. Expression of KLF5 was knocked down with small hairpin RNAs or CRISPR/Cas9 strategies; cells were analyzed in proliferation and gene expression assays, and compared with cells expressing control vectors. Cells were subcutaneously injected into flanks of syngeneic mice and tumor growth was assessed.
RESULTS: Of the 96 PDAC samples analyzed, 73% were positive for KLF5 (defined as nuclear staining in more than 5% of tumor cells). Pancreata from Ptf1a-CreERTM;LSL-KrasG12D mice contained ADM and PanIN lesions, which contained high levels of nuclear KLF5 within these structures. In contrast, Ptf1a-CreERTM;LSL-KrasG12D;Klf5fl/fl mice formed fewer PanINs. After cerulein administration, Ptf1a-CreERTM;LSL-KrasG12D mice formed more extensive ADM than Ptf1a-CreERTM;LSL-KrasG12D;Klf5fl/fl mice. Pancreata from Ptf1a-CreERTM;LSL-KrasG12D;Klf5fl/fl mice had increased expression of the tumor suppressor NDRG2 and reduced phosphorylation (activation) of STAT3, compared with Ptf1a-CreERTM;LSL-KrasG12D mice. In UN-KC-6141 cells, PI3K and MEK signaling increased expression of KLF5; a high level of KLF5 increased proliferation. Cells with knockdown of Klf5 had reduced proliferation, compared with control cells, had reduced expression of ductal markers, and formed smaller tumors (71.61 ± 30.79 mm3 vs 121.44 ± 34.90 mm3 from control cells) in flanks of mice.
CONCLUSION: Levels of KLF5 are increased in human PDAC samples and in PanINs of Ptf1a-CreERTM;LSL-KrasG12D mice, compared with controls. KLF5 disruption increases expression of NDRG2 and reduces activation of STAT3 and reduces ADM and PanINs formation in mice. Strategies to reduce KLF5 activity might reduce progression of acinar cells from ADM to PanIN and pancreatic tumorigenesis.

PMID: 29248441 [PubMed - indexed for MEDLINE]

Permalink for 'c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.'

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.

Fetched: May 5th, 2018, 5:00am GMT

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.

Virchows Arch. 2018 May 02;:

Authors: La Rosa S, Bernasconi B, Vanoli A, Sciarra A, Notohara K, Albarello L, Casnedi S, Billo P, Zhang L, Tibiletti MG, Sessa F

Abstract
The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.

PMID: 29721608 [PubMed - as supplied by publisher]

Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

Fetched: May 4th, 2018, 5:00am GMT

Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

Ann Oncol. 2017 12 01;28(12):3108

Authors: Teyssonneau D, Cousin S, Italiano A

PMID: 29045656 [PubMed - indexed for MEDLINE]

[Clinicopathologic characterisitics of pancreatic acinar cell carcinomas].

Fetched: April 26th, 2018, 5:00am GMT

[Clinicopathologic characterisitics of pancreatic acinar cell carcinomas].

Zhonghua Bing Li Xue Za Zhi. 2018 Apr 08;47(4):274-278

Authors: Ding XH, Wang ZB, Qiu XM

Abstract
Objective: To investigate clinical, pathological and immunohistochemical features of pancreatic acinar cell carcinoma. Methods: A retrospective review of surgical and pathological databases between 2011 and 2016 at PLA General Hospital was collected and 14 cases of acinar cell carcinoma (ACC) of the pancreas were identified. EnVision immunohistochemistry was used to detect the expression of Trypsin, bcl-10 and cytokeratin(CK) proteins. Results: The patients included nine cases of pure ACC, 3 cases of mixed acinar ductal carcinoma, 1 case of mixed acinar-neuroendocrine carcinoma and acinar-ductal-neuroendocrine carcinoma, respectively. Tumors involved different anatomic locations of the pancreas, including eight involving the head of pancreas, four in the body and tail, one in the uncinate process and one in a heterotopic pancreas. Two patients had lymph node and liver metastases before surgery. Microscopically, the tumor was hypercellular with less fibroblastic proliferation and tumor cells arranged in acinar or solid pattern. The well differentiated tumor cells showed eosinophilic, granular cytoplasm with single prominent nucleoli, while the poorly differentiated tumor cells tended to grow in solid sheets. Immunohistochemically, the tumor cells were positive for pan-cytokeratin (14/14), Trypsin (12/14) and bcl-10 (11/14). Stains for CK7 and CK19 were negative (11/14 and 3/4). According to the pTNM staging, there were 7 cases at stageⅠ, 3 at stage ⅡA, 3 at stage Ⅲ and 1 at stage Ⅳ. With average postoperative follow-up of 6-58 months, the median disease-free survival time was 16 months. Conclusions: Pancreatic acinar cell carcinoma is a rare and relatively indolent malignant tumor with characteristic histopathological and immunohistochemical features. Accurate pathological diagnosis plays an important role in patients' treatment and evaluation of prognosis.

PMID: 29690667 [PubMed - in process]

Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival.

Fetched: April 26th, 2018, 5:00am GMT

Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival.

Otolaryngol Head Neck Surg. 2018 Apr 01;:194599818771926

Authors: Morse E, Fujiwara RJT, Husain Z, Judson B, Mehra S

Abstract
Objective To characterize the epidemiology of pediatric salivary cancer and associate patient, tumor, and treatment factors with treatment modality and survival. Study Design Cross-sectional analysis. Setting US national database. Subjects and Methods We identified 588 patients 19 years or younger diagnosed with salivary cancer in the National Cancer Database 2004-2013. We characterized patient, tumor, and treatment factors as proportions and associated these factors with treatment modality and overall survival via multivariable logistic regression and multivariable Cox proportional hazards regression, respectively. Results In total, 588 patients were included. Mucoepidermoid carcinoma was identified in 234 of 588 patients (40%) and acinar cell carcinoma in 215 of 588 (37%). Parotid tumors were seen in 504 (86%) of patients. Surgery alone was used to treat 351 (60%) of patients; surgery plus adjuvant radiation was used to treat 145 (25%). Overall 5-year survival was 93%. Controlling for patient and tumor characteristics, treatment with surgery and radiation vs surgery alone was associated with improved overall survival (hazard ratio [HR] = 0.15; 95% confidence interval [CI], 0.02-0.92; P = .041). High tumor grade was associated with decreased overall survival (HR = 33.17; 95% CI, 5.89-186.8; P < .001). Treatment with surgery plus radiation remained associated with improved overall survival in the subset of patients with high tumor grade (HR = 0.12; 95% CI, 0.02-0.64; P = .014). Conclusion Tumor grade is an important predictor of survival in pediatric patients with salivary gland cancer. Surgery plus adjuvant radiation vs surgery alone is associated with improved overall survival and may be considered for high-risk patients, particularly those with high-grade tumors.

PMID: 29688836 [PubMed - as supplied by publisher]

Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers.

Fetched: April 21st, 2018, 5:00am GMT

Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers.

Head Neck Pathol. 2018 Apr 18;:

Authors: Khurram SA, Speight PM

Abstract
DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated duct marker. However, its specificity and distribution is not well established. The aim of this study was to evaluate the diagnostic utility of DOG-1 expression in SGT in addition to comparing it with myoepithelial markers. Normal salivary tissue and SGT (n = 184) were examined for expression of DOG1 and a range of myoepithelial markers. SGT included: acinic cell carcinoma (ACC, n = 15), secretory carcinoma (SC, n = 9), pleomorphic adenoma (PA, n = 49), carcinoma ex-PA (Ca ex-PA, n = 11), adenoid cystic carcinoma (AdCC, n = 20), polymorphous adenocarcinoma (PAC, n = 6), myoepithelioma (n = 6), myoepithelial carcinoma (MC, n = 2), basal cell adenoma (BCA, n = 14), canalicular adenoma (CA, n = 19), mucoepidermoid carcinoma (MEC, n = 11), oncocytoma (n = 2), adenocarcinoma NOS (AdNOS, n = 4), basal cell adenocarcinoma (BCAC, n = 2), salivary duct carcinoma (SDC, n = 3) and papillary cystadenocarcinoma (PCAC, n = 1). Normal acini and ACC (14/15) showed strong luminal DOG1 staining; SC were largely negative with only focal expression in 3/9 cases. Luminal staining was seen in PA (14/49), PAC (4/6), Ca ex-PA (4/11) and AdCC (6/20). 8/11 MEC showed luminal and/or mucous cell staining. No staining was seen in myoepithelioma, MC, CA, adNOS and BCAC. BCA showed strong staining of myoepithelial cells in some cases (5/14). Variable myoepithelial DOG1 staining was seen in PA, Ca ex PA, BCA, SDC and PCAC which was not as consistent as myoepithelial markers such as calponin, p63 and αSMA. Absence of DOG1 can differentiate ACC from SC, but staining is variable in PA, PLGA and Ca ex-PA. Myoepithelial staining in some tumours but not in normal gland suggests a wider distribution in SGT than originally envisaged.

PMID: 29671211 [PubMed - as supplied by publisher]

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma.

Fetched: April 20th, 2018, 5:00am GMT

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma.

World J Gastrointest Oncol. 2018 Apr 15;10(4):103-107

Authors: Richard C, Niogret J, Boidot R, Ghiringhelli F

Abstract
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses. The analyses revealed in the liver metastasis an amplification of the EGFR gene. Accordingly, the patient was treated with off-label usage of panitumumab. We observed rapid response with necrosis of the liver metastasis, while no efficacy was observed in the primary tumor. An exome analysis of the primary tumor revealed amplification of HER2 and MET with EGFR amplification. Such amplifications are known as a resistance mechanism to antiEGFR therapy. Our results suggest that exome analysis may be helpful to highlight targets in rare cancers, such as PACC. EGFR amplification in this pathology should be determined and could be used as a biomarker to propose antiEGFR therapy.

PMID: 29666669 [PubMed]

Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing good response to chemotherapy.

Fetched: April 18th, 2018, 5:00am GMT

Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing good response to chemotherapy.

J Gastroenterol Hepatol. 2018 May;33(5):977

Authors: Laino ME, Ragucci M, Klimstra DS, Mannelli L

PMID: 29659083 [PubMed - in process]

A Tumor Localized in the Portal Vein.

Fetched: April 18th, 2018, 5:00am GMT

A Tumor Localized in the Portal Vein.

Gastroenterology. 2017 Apr;152(5):e7-e9

Authors: Nakayama Y, Fukuda A, Kodama Y

PMID: 28263722 [PubMed - indexed for MEDLINE]

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini.

Fetched: March 28th, 2018, 5:00am GMT

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini.

Breast Cancer Res. 2017 Jun 07;19(1):68

Authors: Seifert A, Posern G

Abstract
BACKGROUND: Myocardin-related transcription factors (MRTF) A and B link actin dynamics and mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role in human mammary epithelial cells remains unclear.
METHODS: Three-dimensional cultures of human mammary epithelial MCF10A cells were used to model acinar morphogenesis. Stable MRTF-A knockdown, MRTF-A/B rescue and MRTF-A/B overexpression was established to characterize the functional role during morphogenesis using confocal microscopy and expression analysis. Breast cancer patient databases were analyzed for MRTF-A expression.
RESULTS: We showed that a precise temporal control of MRTFs is required for normal morphogenesis of MCF10A mammary acini. MRTF transcriptional activity, but not their protein amounts, is transiently induced during 3D acini formation. MRTF-A knockdown dramatically reduces acini size and prevents lumen formation. These effects are rescued by re-expression of MRTF-A, and partially by MRTF-B. Conversely, overexpression of MRTF-A and MRTF-B increases acini size, resulting in irregular spheroids without lumen and defective apico-basal polarity. These phenotypes correlate with deregulated expression of cell cycle inhibitors p21/Waf1, p27/Kip1 and altered phosphorylation of retinoblastoma protein. In MRTF overexpressing spheroids, proliferation and apoptosis are simultaneously increased at late stages, whilst neither occurs in control acini. MRTFs interfere with anoikis of the inner cells and cause an integrin switch from α6 to α5, repression of E-cadherin and induction of mesenchymal markers vimentin, Snai2 and Zeb1. Moreover, MRTF-overexpressing spheroids are insensitive to alteration in matrix stiffness. In two breast cancer cohorts, high expression of MRTF-A and known target genes was associated with decreased patient survival.
CONCLUSION: MRTF-A is required for proliferation and formation of mammary acini from luminal epithelial cells. Conversely, elevated MRTF activity results in pre-malignant spheroid formation due to defective proliferation, polarity loss and epithelial-mesenchymal transition.

PMID: 28592291 [PubMed - indexed for MEDLINE]

Atypical flat lesions derive from pancreatic acinar cells.

Fetched: March 26th, 2018, 5:00am GMT

Atypical flat lesions derive from pancreatic acinar cells.

Pancreatology. 2017 May - Jun;17(3):350-353

Authors: von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I

Abstract
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli.
METHODS: Histological analyses were performed in a murine PDAC model that specifically expresses oncogenic Kras in adult pancreatic acinar cells. Occurrence, characterization, and lineage tracing of AFLs were investigated.
RESULTS: Upon expression of oncogenic Kras in adult pancreatic acinar cells, AFLs with typical morphology and expression profile arise. Lineage tracing confirmed that the AFLs were of acinar origin.
CONCLUSIONS: Using a murine PDAC model, this study identifies pancreatic acinar cells as a cellular source for AFLs.

PMID: 28473229 [PubMed - indexed for MEDLINE]

Pancreatic panniculitis as a presentation symptom of acinar cell carcinoma.

Fetched: March 14th, 2018, 5:00am GMT

Pancreatic panniculitis as a presentation symptom of acinar cell carcinoma.

Rev Esp Enferm Dig. 2018 Mar 12;110:

Authors: de Frutos Rosa D, Espinosa Taranilla L, González de Canales de Simón P, Vélez Velázquez MD, Guirado Koch C

Abstract
Pancreatic panniculitis is a rare skin manifestation associated with pancreatic conditions. This condition has similar characteristics to those of other panniculitis types and its course parallels the triggering condition and may occasionally precede it. We report the case of a female patient with asymptomatic pancreatic panniculitis; the etiologic study identified a pancreatic acinar cell carcinoma with liver metastases.

PMID: 29527901 [PubMed - as supplied by publisher]

The anteroposterior diameter of nodules in the risk assessment of papillary thyroid microcarcinoma.

Fetched: March 10th, 2018, 5:00am GMT

The anteroposterior diameter of nodules in the risk assessment of papillary thyroid microcarcinoma.

Medicine (Baltimore). 2018 Mar;97(10):e9712

Authors: Huang K, Gao N, Zhai Q, Bian D, Wang D, Wang X

Abstract
This study investigates the application of ultrasound, especially the anteroposterior diameter of nodules in the malignancy and metastasis risk assessment of papillary thyroid microcarcinoma through a retrospective analysis of 500 cases of thyroid nodule ultrasonography.We selected 500 patients with thyroid nodules (maximum nodule diameter ≤2.0 cm) that had been diagnosed clinically and graded TI-RADS 4c by ultrasonography and surgically treated. Among these, there were 258 cases of pathologically diagnosed papillary thyroid microcarcinoma, 72 cases of nodular goiter or adenoma, 137 cases of papillary thyroid carcinoma, 28 cases of acinar cell carcinoma, and 5 cases of undifferentiated carcinoma. In all cases, color Doppler ultrasonography had been performed preoperatively to determine the size and number of nodules, surrounding lymph node metastasis, and TI-RADS grading. Cases of papillary thyroid microcarcinoma diagnosed by pathology were selected as the study group, and cases of nodular goiter or adenoma as the control group. Each group was further subdivided based on the anteroposterior, vertical, and transverse nodule diameters. Intergroup statistical analysis was also performed. Receiver operating characteristic (ROC) curve analysis was conducted on the study and control groups based on the anteroposterior nodule diameters, and the optimal critical value for malignancy risk was determined. Thyroid nodules in the study group were divided into groups based on the presence or absence of lymph node metastasis. Based on the anteroposterior nodule diameter, ROC curve analysis was performed, and the optimal critical value for metastasis risk was determined.There were 500 cases of malignant nodules diagnosed by ultrasound. Among these, there were 428 cases of malignant nodules diagnosed by pathology. The coincidence rate of the ultrasound diagnosis with pathological diagnosis was 85.60%. While, interestingly, There was a significant statistical difference between the study and control groups based on the anteroposterior nodule diameter. When the anteroposterior nodule diameter was 0.7 cm, sensitivity of malignant diagnosis was 76.70% and specificity of that was 66.70%, and the Youden index was the highest. The lymph node metastasis rate for papillary thyroid microcarcinoma was 13.95%. Within this group, the lymph node metastasis rate for nodules ≥0.9 cm (anteroposterior diameter) was 38.46%. When the anteroposterior nodule diameter was equal to 0.9 cm, sensitivity of diagnosis was 83.30%, and specificity of that was 77.80%, and the Youden index was the highest.The anteroposterior diameter of thyroid nodules is more suitable for assessing their malignancy with 0.7 cm, which can be used as the critical value. Nodules ≥ 0.7 cm require surgical treatment, and those <0.7 cm can be observed. An anteroposterior diameter of 0.9 cm can be used as the critical value for assessing the metastasis risk of malignant thyroid nodules. During surgery, the dissection of central cervical lymph nodes is required for nodules ≥0.9 cm.

PMID: 29517693 [PubMed - in process]

BRAF gene rearrangements can be identified by FISH studies in pancreatic acinar cell carcinoma.

Fetched: March 8th, 2018, 5:00am GMT

BRAF gene rearrangements can be identified by FISH studies in pancreatic acinar cell carcinoma.

Pathology. 2018 Mar 02;:

Authors: Chou A, Kim Y, Samra JS, Pajic M, Gill AJ

PMID: 29506751 [PubMed - as supplied by publisher]

Acinic Cell Carcinoma - News-Medical.net

Posted: June 20th, 2018, 11:23pm GMT

News-Medical.net

【暖势力】展现韧力宣扬癌症非绝症．抗癌女斗士远征俄高峰 - 星洲网 Sin Chew Daily (新闻发布)

Posted: May 21st, 2018, 7:25am GMT

星洲网 Sin Chew Daily (新闻发布)

【暖势力】展现韧力宣扬癌症非绝症．抗癌女斗士远征俄高峰
星洲网 Sin Chew Daily (新闻发布)
但到了2014年，癌症再度找上她，此番前来的是腺泡细胞癌（Acinic Cell Carcinoma），而她选择通过割除右侧腮腺手术来保命，以继续她冒险的人生旅程。迈拉代表马来西亚登上厄尔布鲁斯峰，山上一望无际的风景和强风飞雪 ...

The Spectrum of Triple-Negative Breast Disease - Am J Pathology

Posted: July 21st, 2017, 10:03pm GMT

Am J Pathology

The Spectrum of Triple-Negative Breast Disease
Am J Pathology
Whereas fairly common in acinic cell carcinoma, it is a rare event in the salivary gland–like tumors of the breast and solid papillary carcinoma with reverse polarity. ∗It should be noted that evidence for the presence of PRKD1 E710D mutations or PRKD1 ...

The Spectrum of Triple-Negative Breast Disease - Am J Pathology

Posted: July 21st, 2017, 10:03pm GMT

Am J Pathology

Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype - Nature.com

Posted: August 20th, 2015, 7:27am GMT

Nature.com

Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype
Nature.com
Diegel, C. R., Cho, K. R., El-Naggar, A. K., Williams, B. O. & Lindvall, C. Mammalian target of rapamycin-dependent acinar cell neoplasia after inactivation of Apc and Pten in the mouse salivary gland: implications for human acinic cell carcinoma ...

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study - Nature.com

Posted: June 19th, 2015, 9:41am GMT

Nature.com

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study
Nature.com
We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin ...

Permalink for 'Four-Year Survival of a Patient With Spinal Metastatic Acinic Cell Carcinoma After a Total En Bloc Spondylectomy and Reconstruction With a Frozen Tumor-Bearing Bone Graft.'

Four-Year Survival of a Patient With Spinal Metastatic Acinic Cell Carcinoma After a Total En Bloc Spondylectomy and Reconstruction With a Frozen Tumor-Bearing Bone Graft.

Fetched: June 20th, 2018, 5:00am GMT

Four-Year Survival of a Patient With Spinal Metastatic Acinic Cell Carcinoma After a Total En Bloc Spondylectomy and Reconstruction With a Frozen Tumor-Bearing Bone Graft.

Orthopedics. 2018 Jun 18;:1-4

Authors: Sangsin A, Murakami H, Shimizu T, Kato S, Tsuchiya H

Abstract
Acinic cell carcinoma metastasizing to the spine is extremely rare. The authors present a case of acinic cell carcinoma of the parotid gland with subsequent lung and spinal metastases, treated with en bloc spondylectomy. A 41-year-old man presented with a left parotid mass. After being diagnosed with acinic cell carcinoma, he underwent a total parotidectomy. Imaging studies revealed a metastatic osteoblastic lesion in the T4 vertebral body and multiple lung metastases. Total en bloc spondylectomy and reconstruction with a frozen tumor-bearing bone graft were performed to treat the T4 metastasis. Lung metastases were treated with periodic radiofrequency ablation. At the 48-month follow-up, there was no local recurrence of the lesions, and the lung metastases were controlled. The bone graft had fused with the adjacent vertebrae, and the patient had full neurological function and normal daily activities. This report indicates satisfactory long-term outcomes of total en bloc spondylectomy and reconstruction with frozen tumor-bearing bone graft in a patient with acinic cell carcinoma with spinal metastasis. It also emphasizes the benefits of radical resection of spinal metastasis even in cases with multiple organ metastases. [Orthopedics. 201x; xx(x):xx-xx.].

PMID: 29913031 [PubMed - as supplied by publisher]

Systemic therapy in non-conventional cancers of the larynx.

Fetched: June 20th, 2018, 5:00am GMT

Systemic therapy in non-conventional cancers of the larynx.

Oral Oncol. 2018 Jul;82:61-68

Authors: Tan E, Mody MD, Saba NF

Abstract
Laryngeal cancer (LC) remains a challenging disease to treat. The majority of LCs diagnosed worldwide are squamous cell carcinomas (SCC), and current treatment guidelines are designed to address conventional laryngeal SCC. However, several histologically rare tumor types can originate in the larynx. There is a lack of guidelines regarding the best therapeutic approaches to these tumors and their treatment is often modeled after their recommended management at non-laryngeal sites. Understanding the role for systemic therapy in these rare tumors is important, especially for patients with advanced disease or those who are not surgical candidates. We provide in this manuscript a detailed and comprehensive overview of systemic therapy considerations for the following histologic tumor types of the larynx: verrucous carcinoma (VC), HPV-related SCC, basaloid SCC (BSCC), lymphoepithelial carcinoma (LEC), adenosquamous carcinoma (ASC), typical and atypical carcinoid, small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), NUT midline carcinomas (NUTMC), melanoma, adenoid cystic carcinoma, rhabdomyosarcoma (RMS), malignant fibrous histiocytoma (MFH), lymphoma, mucoepidermoid carcinoma (MEC), acinic cell carcinoma, and spindle cell carcinoma (SpCC).

PMID: 29909903 [PubMed - in process]

Outcomes and prognostic factors for parotid acinic cell Carcinoma: A National Cancer Database study of 2362 cases.

Fetched: June 20th, 2018, 5:00am GMT

Outcomes and prognostic factors for parotid acinic cell Carcinoma: A National Cancer Database study of 2362 cases.

Oral Oncol. 2018 Jul;82:53-60

Authors: Scherl C, Kato MG, Erkul E, Graboyes EM, Nguyen SA, Chi AC, Morgan PF, Day TA

Abstract
OBJECTIVES: To evaluate the demographics, clinical features, survival outcomes, and prognostic indicators of patients with acinic cell carcinoma (ACC) of the parotid gland with emphasis on the roles of grade, tumor size, and nodal status in survival.
MATERIALS AND METHODS: A retrospective analysis of cases diagnosed between 2004 and 2012 from the National Cancer Database was performed. Multivariable logistic regression was used to determine factors associated with survival.
RESULTS: 2362 cases were identified. Most patients were females (61.3%) and Caucasian (85.4%) with a median age of 54 years (range, 18-90 years). Most tumors were <3 cm in size (75.8%). Regional metastases and high-grade histology were rare (8.2%, 5.1%). All patients received surgery as primary treatment with 42.7% of patients receiving adjuvant radiation therapy or chemoradiotherapy. 5 year overall survival was 88.6%. On multivariable analysis, age >70 years (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 5.64-17.91), high-grade (HR: 5.30, 95% CI: 3.39-8.29), tumor size of 3 to 6 cm (HR: 1.53, 95% CI: 1.10-2.12), tumor size >6 cm (HR: 2.98, 95% CI: 1.681-5.289), pN2+ (HR: 3.14, 95% CI: 2.10-4.69), T4 (HR: 2.89, 95% CI: 1.74-4.80) were significant prognosticators.
CONCLUSION: Although patients with ACC generally are considered to have a favorable prognosis, an aggressive subgroup with poor outcomes was identified. This group is characterized by high-grade, advanced T classification, tumors larger than 3 cm, with regional metastases and age greater than 70 years. Histologic grade is a substantially stronger predictor of survival than T and N classifications.

PMID: 29909902 [PubMed - in process]

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression.

Fetched: June 15th, 2018, 5:00am GMT

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression.

Cell Rep. 2017 Oct 24;21(4):966-978

Authors: Ferreira RMM, Sancho R, Messal HA, Nye E, Spencer-Dene B, Stone RK, Stamp G, Rosewell I, Quaglia A, Behrens A

PMID: 29069604 [PubMed - indexed for MEDLINE]

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.

Fetched: June 15th, 2018, 5:00am GMT

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.

Cell Signal. 2017 Dec;40:91-98

Authors: Datta A, Sandilands E, Mostov KE, Bryant DM

PMID: 28888686 [PubMed - indexed for MEDLINE]

Aging dependent effect of nuclear tau.

Fetched: June 13th, 2018, 5:00am GMT

Aging dependent effect of nuclear tau.

Brain Res. 2017 Dec 15;1677:129-137

Authors: Gil L, Federico C, Pinedo F, Bruno F, Rebolledo AB, Montoya JJ, Olazabal IM, Ferrer I, Saccone S

PMID: 28974363 [PubMed - indexed for MEDLINE]

Bioengineered Submucosal Organoids for In Vitro Modeling of Colorectal Cancer.

Fetched: June 13th, 2018, 5:00am GMT

Bioengineered Submucosal Organoids for In Vitro Modeling of Colorectal Cancer.

Tissue Eng Part A. 2017 Oct;23(19-20):1026-1041

Authors: Devarasetty M, Skardal A, Cowdrick K, Marini F, Soker S

PMID: 28922975 [PubMed - indexed for MEDLINE]

Mucinous adenocarcinoma of prostate and prostatic adenocarcinoma with mucinous components: a clinicopathological analysis of 143 cases.

Fetched: June 13th, 2018, 5:00am GMT

Mucinous adenocarcinoma of prostate and prostatic adenocarcinoma with mucinous components: a clinicopathological analysis of 143 cases.

Histopathology. 2017 Oct;71(4):641-647

Authors: Samaratunga H, Delahunt B, Srigley JR, Yaxley J, Johannsen S, Coughlin G, Gianduzzo T, Kua B, Patterson I, Nacey JN, Egevad L

PMID: 28590015 [PubMed - indexed for MEDLINE]

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate.

Fetched: June 11th, 2018, 5:00am GMT

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate.

Hum Pathol. 2018 Jun 06;:

Authors: Xue W, Xin Z, Zhang Y, Jiang Z, Zhao L, Fan L, Wang Y, Xie S, Shangguan X, Zhu Y, Pan J, Liu Q, Huang Y, Dong B

PMID: 29885405 [PubMed - as supplied by publisher]

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

Fetched: June 9th, 2018, 5:00am GMT

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

Head Neck Pathol. 2018 Jun 06;:

Authors: Mossinelli C, Pigni C, Sovardi F, Occhini A, Preda L, Benazzo M, Morbini P, Pagella F

Abstract
Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

PMID: 29876739 [PubMed - as supplied by publisher]

Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

Fetched: June 8th, 2018, 5:00am GMT

Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

J Gastrointest Surg. 2017 Dec;21(12):2132-2134

Authors: Dogeas E, Peng L, Choti MA

PMID: 28681213 [PubMed - indexed for MEDLINE]

Clinical characteristics and prognosis of patients with lung adenosquamous carcinoma after surgical resection: results from two institutes.

Fetched: June 2nd, 2018, 5:00am GMT

Clinical characteristics and prognosis of patients with lung adenosquamous carcinoma after surgical resection: results from two institutes.

J Thorac Dis. 2018 Apr;10(4):2397-2402

Authors: Zhu L, Jiang L, Yang J, Gu W, He J

PMID: 29850145 [PubMed]

Accuracy of preoperative fine needle aspiration in diagnosis of malignant parotid tumors.

Fetched: June 1st, 2018, 5:00am GMT

Accuracy of preoperative fine needle aspiration in diagnosis of malignant parotid tumors.

Saudi Med J. 2017 Oct;38(10):1000-1006

Authors: Marzouki HZ, Altabsh MA, Albakrei MO, Al-Khatib TA, Merdad MA, Farsi NJ

PMID: 28917063 [PubMed - indexed for MEDLINE]

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.

Fetched: May 30th, 2018, 5:00am GMT

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.

Oncol Lett. 2018 Jun;15(6):8973-8982

Authors: Li C, Zheng X, Han Y, Lv Y, Lan F, Zhao J

PMID: 29805633 [PubMed]

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Fetched: May 24th, 2018, 5:00am GMT

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Mod Pathol. 2018 May 21;:

Authors: Suzuki M, Nakatani Y, Ito H, Narimatsu H, Yamada K, Yoshioka E, Washimi K, Okubo Y, Kawachi K, Miyagi Y, Yokose T

PMID: 29785018 [PubMed - as supplied by publisher]

[Acquired cystic kidney disease-associated renal cell carcinoma: a clinicopathologic study of three cases].

Fetched: May 24th, 2018, 5:00am GMT

[Acquired cystic kidney disease-associated renal cell carcinoma: a clinicopathologic study of three cases].

Zhonghua Bing Li Xue Za Zhi. 2018 May 08;47(5):366-371

Authors: Zhang W, Xu LL, Yu WJ, Wang Q, Jiang YX, Liu Y, Li YJ

PMID: 29783804 [PubMed - in process]

Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles.

Fetched: May 24th, 2018, 5:00am GMT

Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles.

Int J Oncol. 2017 Oct;51(4):1035-1044

Authors: Mattheolabakis G, Wang R, Rigas B, Mackenzie GG

PMID: 28849098 [PubMed - indexed for MEDLINE]

Molecular Diagnostics in the Neoplasms of the Pancreas, Liver, Gallbladder, and Extrahepatic Biliary Tract: 2018 Update.

Fetched: May 21st, 2018, 5:00am GMT

Molecular Diagnostics in the Neoplasms of the Pancreas, Liver, Gallbladder, and Extrahepatic Biliary Tract: 2018 Update.

Clin Lab Med. 2018 Jun;38(2):367-384

Authors: Zhang L, Bluth MH, Bhalla A

PMID: 29776636 [PubMed - in process]

Novel interleukin-33 and its soluble ST2 receptor as potential serum biomarkers in parotid gland tumors.

Fetched: May 17th, 2018, 5:00am GMT

Novel interleukin-33 and its soluble ST2 receptor as potential serum biomarkers in parotid gland tumors.

Exp Biol Med (Maywood). 2018 May;243(9):762-769

Authors: Pawel S, Maciej M, Maciej Z, Bogdan M, Monika AS

Abstract
An increasing number of patients with parotid gland tumors have been observed in recent years. The relationship between the immune system and tumor formation is thoroughly investigated. However, newly discovered molecules offer a new insight into the pathophysiology of malignancies. It would be ideal to find an easily determinable biomarker of tumor existence, its malignant potential or a biomarker suggesting the probability of disease recurrence. Our study is the first to examine serum concentrations of IL-33 and its sST2 receptor in patients with various types of parotid gland tumors. Serum IL33, sST2, IL-4 and IL-10 concentrations were determined in patients with benign and malignant parotid gland tumors (pleomorphic adenoma, Warthin's tumor, myoepithelioma and acinic cell carcinoma). We observed for the first time that serum IL-33 level was significantly elevated in patients with various types of parotid gland tumors and sST2 levels were significantly higher in pleomorphic adenoma and acinic cell carcinoma patients compared to the controls. Our results demonstrate for the first time that serum IL-33 and its sST2 receptor may be important factors in the pathology of parotid gland tumors. Although our results are promising, further investigations are required to detect if serum concentrations of those molecules may be a biomarker in parotid gland tumors. Impact statement Parotid gland tumors seem to be an increasingly important medical challenge, mostly due to a noticeable increase in the incidence. It would be crucial to find an easily determinable biomarker of tumor existence, its recurrence or malignant potential. We observed for the first time that serum IL-33 level was significantly elevated in patients with various types of parotid gland tumors and its sST2 receptor levels were significantly higher in pleomorphic adenoma and acinic cell carcinoma patients compared to the controls. We believe that our study helps to understand the biology of the tumors and a potential role of a relatively newly identified cytokine IL-33 in the pathophysiology of the parotid gland tumors.

PMID: 29763370 [PubMed - in process]

GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.

Fetched: May 17th, 2018, 5:00am GMT

GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.

Proc Natl Acad Sci U S A. 2017 05 16;114(20):E4020-E4029

Authors: Shen J, Ha DP, Zhu G, Rangel DF, Kobielak A, Gill PS, Groshen S, Dubeau L, Lee AS

PMID: 28461470 [PubMed - indexed for MEDLINE]

What is your diagnosis? Mandibular mass in a cat.

Fetched: May 16th, 2018, 5:00am GMT

What is your diagnosis? Mandibular mass in a cat.

Vet Clin Pathol. 2018 May 14;:

Authors: Newman AW, Asakawa MG, Stokol T

PMID: 29758098 [PubMed - as supplied by publisher]

The screening and electron microscopy observation of mammary analogue secretory carcinoma in Chinese.

Fetched: May 14th, 2018, 5:00am GMT

The screening and electron microscopy observation of mammary analogue secretory carcinoma in Chinese.

J Craniomaxillofac Surg. 2017 Oct 19;:

Authors: Zhong Y, Liu L, Qi B, Song X, Shen L, Li H

PMID: 29752049 [PubMed - as supplied by publisher]

Central Acinic Cell Carcinoma of the Mandible Simulating as Benign Odontogenic Lesion: A Case Report.

Fetched: May 13th, 2018, 5:00am GMT

Central Acinic Cell Carcinoma of the Mandible Simulating as Benign Odontogenic Lesion: A Case Report.

Iran J Med Sci. 2018 Mar;43(2):223-226

Authors: Bajpai M, Pardhe N, Chandolia B, Arora M

PMID: 29749993 [PubMed]

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

Fetched: May 11th, 2018, 5:00am GMT

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

Gastroenterology. 2018 04;154(5):1494-1508.e13

Authors: He P, Yang JW, Yang VW, Bialkowska AB

PMID: 29248441 [PubMed - indexed for MEDLINE]

Immunohistochemical Detection of Proliferative Marker Ki-67 in Benign and Malignant Salivary Gland Tumors.

Fetched: May 9th, 2018, 5:00am GMT

Immunohistochemical Detection of Proliferative Marker Ki-67 in Benign and Malignant Salivary Gland Tumors.

J Contemp Dent Pract. 2018 Apr 01;19(4):375-383

Authors: Bussari S, Ganvir SM, Sarode M, Jeergal PA, Deshmukh A, Srivastava H

Abstract
Introduction: Salivary gland tumors are the most histologically heterogeneous group of tumors with the greatest diversity of morphologic features among their cells and tissues. The present study was aimed at assessing the validity of Ki-67, a cell proliferation marker, as a prognostic factor in benign and malignant salivary gland tumors and to study whether it is related to age, sex, anatomical site, and size of the lesion in salivary gland tumors. Materials and methods: A retrospective study consisted of benign salivary gland tumors (BSGTs) (n = 15), malignant salivary gland tumors (n = 18), and normal salivary gland parenchyma (n = 15). Results: There was a significant difference of Ki-67 labeling index (LI, %) in normal salivary gland parenchyma, BSGTs, and malignant salivary gland tumors. The Ki-67 LI (%) in normal salivary gland parenchyma is negligible (0.27 ± 0.31%), whereas malignant salivary gland tumors showed very high Ki-67 LI (%) of 18.79 ± 18.06% compared with BSGTs being 0.76 ± 2.02%. There was a significant correlation statistically of mean ± standard deviation (SD) of Ki-67 LI (%) with the age of the patients being the maximum (32.68 ± 15.87%) in the 50 to 59 years age group, whereas sex, site of the lesion, and size of the lesion in salivary gland tumors had no significant correlation. Conclusion: The Ki-67 is a useful marker for assessing prolif-erative potential of tumors. Clinical significance: The Ki-67 LI% can be used as a reliable adjuvant diagnostic tool to differentiate between the subtypes and grading of certain malignant tumors, such as mucoepi-dermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), and acinic cell carcinoma (AcCC), which are usually difficult to diagnose on histopathological criteria alone. Keywords: Immunohistochemistry, Ki-67, Salivary gland neoplasms.

PMID: 29728539 [PubMed - in process]

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.

Fetched: May 5th, 2018, 5:00am GMT

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.

Virchows Arch. 2018 May 02;:

Authors: La Rosa S, Bernasconi B, Vanoli A, Sciarra A, Notohara K, Albarello L, Casnedi S, Billo P, Zhang L, Tibiletti MG, Sessa F

PMID: 29721608 [PubMed - as supplied by publisher]

Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

Fetched: May 4th, 2018, 5:00am GMT

Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

Ann Oncol. 2017 12 01;28(12):3108

Authors: Teyssonneau D, Cousin S, Italiano A

PMID: 29045656 [PubMed - indexed for MEDLINE]

[Retrospective analysis of 896 cases of parotid gland tumor].

Fetched: April 26th, 2018, 5:00am GMT

[Retrospective analysis of 896 cases of parotid gland tumor].

Shanghai Kou Qiang Yi Xue. 2017 Dec;26(6):605-609

Authors: Zhao ZG, Gao D, Wang J, Zhang LP

Abstract
PURPOSE: To review the clinical data of patients undergoing operation, in order to summarize the incidence, proportion, clinical examination and diagnostic methods of parotid tumors.
METHODS: Eight hundred and ninty-six cases of parotid gland tumors were collected from 2008 January to 2015 July from department of oral and maxillofacial surgery in Shengjing Hospital of China Medical University. A retrospective study of the clinical data was carried out, including age, gender, tumor location, diagnostic methods and pathological results.
RESULTS: In 896 patients with parotid gland tumor, 432 were male, 464 were female, the ratio was 1:1.07; 431 cases were on the left side, 454 cases were on the right side, 11 cases were bilateral; The proportion of parotid tumor was higher in patients aged 31 to 70 years old. 786 cases were benign, 110 cases were malignant, the ratio of benign to malignant was 7.15:1. Pleomorphic adenoma, Warthin tumor and basal cell adenoma were the most common types of benign tumors, while mucoepidermoid carcinoma, acinic cell carcinoma and adenoid cystic carcinoma accounted for the most of malignant tumors.
CONCLUSIONS: The pathological types of parotid gland tumor are complicated. Clinical examination and imaging features are helpful to diagnosis. The accuracy is high in diagnosis of parotid gland tumor by frozen section, which is useful to assist making treatment plan.

PMID: 29691554 [PubMed - in process]

[Clinicopathologic characterisitics of pancreatic acinar cell carcinomas].

Fetched: April 26th, 2018, 5:00am GMT

[Clinicopathologic characterisitics of pancreatic acinar cell carcinomas].

Zhonghua Bing Li Xue Za Zhi. 2018 Apr 08;47(4):274-278

Authors: Ding XH, Wang ZB, Qiu XM

PMID: 29690667 [PubMed - in process]

Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival.

Fetched: April 26th, 2018, 5:00am GMT

Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival.

Otolaryngol Head Neck Surg. 2018 Apr 01;:194599818771926

Authors: Morse E, Fujiwara RJT, Husain Z, Judson B, Mehra S

PMID: 29688836 [PubMed - as supplied by publisher]

Salivary Secretory Carcinoma With a Novel ETV6-MET Fusion: Expanding the Molecular Spectrum of a Recently Described Entity.

Fetched: April 25th, 2018, 5:00am GMT

Salivary Secretory Carcinoma With a Novel ETV6-MET Fusion: Expanding the Molecular Spectrum of a Recently Described Entity.

Am J Surg Pathol. 2018 Apr 20;:

Authors: Rooper LM, Karantanos T, Ning Y, Bishop JA, Gordon SW, Kang H

Abstract
Secretory carcinoma of the salivary glands, also known as mammary analogue secretory carcinoma, is a recently described tumor characterized by generally indolent clinical behavior and recurrent ETV6-NTRK3 fusions. However, a small subset of recent cases with high-grade histology, aggressive behavior, or alternate molecular findings are expanding the spectrum of this entity. In this case, a 59-year-old female presented with an infiltrative submandibular gland tumor that was originally classified as a high-grade acinic cell carcinoma, papillary-cystic variant. She developed persistent local disease and, 11 years after initial presentation, was found to have widespread metastases. Rereview of her primary tumor highlighted microcystic, papillary, and solid architecture, eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, abundant mitotic figures, and necrosis. Immunostains showed the tumor cells to be positive for S100 and mammaglobin and negative for DOG-1, and fluorescence in situ hybridization highlighted an ETV6 rearrangement, supporting a diagnosis of high-grade secretory carcinoma. Finally, next-generation sequencing demonstrated a novel ETV6-MET fusion. To our knowledge, this is the first ETV6-MET fusion reported in secretory carcinoma. This finding further expands the definition of secretory carcinoma while carrying implications for selecting appropriate targeted therapy.

PMID: 29683815 [PubMed - as supplied by publisher]

Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers.

Fetched: April 21st, 2018, 5:00am GMT

Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers.

Head Neck Pathol. 2018 Apr 18;:

Authors: Khurram SA, Speight PM

PMID: 29671211 [PubMed - as supplied by publisher]

Permalink for 'Analysis of histologic follow-up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology.'

Analysis of histologic follow-up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology.

Fetched: April 20th, 2018, 5:00am GMT

Analysis of histologic follow-up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology.

Cancer Cytopathol. 2018 Apr 18;:

Authors: Liu H, Ljungren C, Lin F, Zarka MA, Chen L

Abstract
BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology is a tiered classification scheme that includes 6 diagnostic categories. Neoplasm, which is 1 of the 6 proposed categories, consists of benign neoplasm and neoplasm of uncertain malignant potential (NUMP). NUMP is reserved for a salivary gland neoplasm without clear distinction between benign and malignant. The objective of this study was to assess the risk of malignancy (ROM) of NUMP.
METHODS: A retrospective analysis was conducted on 656 salivary gland fine-needle aspiration specimens from 2010 to 2016. Cases that qualified as NUMP and had follow-up surgical resections were reviewed and reclassified into basaloid neoplasm (BN) and salivary gland neoplasm with predominant oncocytic cell (SGNOC) groups. The ROM for each group was calculated. Fifty-four salivary gland fine-needle aspirations of NUMP that had surgical follow-up were identified, which included 29 BNs and 25 SGNOCs.
RESULTS: Histologic follow-up for the BN group identified 14 cellular pleomorphic adenomas, 5 basal cell adenomas, 2 benign cystadenomas, 3 adenoid cystic carcinomas, 3 epithelial and myoepithelial carcinomas, 1 basal cell adenocarcinoma, and 1 myoepithelial carcinoma. Histologic follow-up for the SGNOC group revealed 7 nodular oncocytoses, 6 Warthin tumors, 5 oncocytomas, 1 sebaceous adenoma, 1 mucinous cystadenoma, 2 acinic cell carcinomas, 2 mucoepidermoid carcinomas, and 1 mammary analog secretory carcinoma. The ROM was calculated at 24.1% for the NUMP category overall (27.6% for BNs and 20.0% for SGNOCs).
CONCLUSIONS: The ROM of the SGNOC group is similar to that of the BN group but lower than the ROM (35%) proposed by the Milan system. Cancer Cytopathol 2018. © 2018 American Cancer Society.

PMID: 29669190 [PubMed - as supplied by publisher]

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma.

Fetched: April 20th, 2018, 5:00am GMT

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma.

World J Gastrointest Oncol. 2018 Apr 15;10(4):103-107

Authors: Richard C, Niogret J, Boidot R, Ghiringhelli F

PMID: 29666669 [PubMed]

Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing good response to chemotherapy.

Fetched: April 18th, 2018, 5:00am GMT

Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing good response to chemotherapy.

J Gastroenterol Hepatol. 2018 May;33(5):977

Authors: Laino ME, Ragucci M, Klimstra DS, Mannelli L

PMID: 29659083 [PubMed - in process]

A Tumor Localized in the Portal Vein.

Fetched: April 18th, 2018, 5:00am GMT

A Tumor Localized in the Portal Vein.

Gastroenterology. 2017 Apr;152(5):e7-e9

Authors: Nakayama Y, Fukuda A, Kodama Y

PMID: 28263722 [PubMed - indexed for MEDLINE]

Oxidative Stress Markers Patients with Parotid Gland Tumors: A Pilot Study.

Fetched: April 15th, 2018, 5:00am GMT

Oxidative Stress Markers Patients with Parotid Gland Tumors: A Pilot Study.

Biomed Res Int. 2018;2018:4340871

Authors: Sowa P, Misiolek M, Pasinski B, Bartosz G, Soszynski M, Adamczyk-Sowa M, Sadowska-Bartosz I

Abstract
Salivary gland tumors account for 3-6% of tumors of the head and neck. About 80% of salivary gland tumors occur in parotid glands. Oxidative stress (OS) is implicated in the origin, development, and whole-body effects of various tumors. There are no data on the occurrence of OS in the parotid gland tumors. The aim of this study was to ascertain if whole-body OS accompanies parotid gland tumors, based first of all on oxidative modifications of blood serum proteins and other markers of OS in the serum of the patients. The group studied included 17 patients with pleomorphic adenoma, 9 patients with Warthin's tumor, 8 patients with acinic cell carcinoma, and 24 age-matched controls. We found increased concentration of interleukin 4 in patients with acinic cell carcinoma, decreased plasma thiols, increased AOPP concentration, and decreased FRAP of blood serum in all groups of the patients while protein oxidative modifications assessed fluorimetrically, protein carbonyls, protein nitration, malondialdehyde concentration, and serum ABTS⁎-scavenging capacity were unchanged. These data indicate the occurrence of OS in patients with parotid gland tumors and point to various sensitivities of OS markers.

PMID: 29651432 [PubMed - in process]

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini.

Fetched: March 28th, 2018, 5:00am GMT

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini.

Breast Cancer Res. 2017 Jun 07;19(1):68

Authors: Seifert A, Posern G

PMID: 28592291 [PubMed - indexed for MEDLINE]

Permalink for 'Salivary gland cancer patient-derived xenografts enable characterization of cancer stem cells and new gene fusions associated with tumor progression.'

Salivary gland cancer patient-derived xenografts enable characterization of cancer stem cells and new gene fusions associated with tumor progression.

Fetched: March 22nd, 2018, 5:00am GMT

Salivary gland cancer patient-derived xenografts enable characterization of cancer stem cells and new gene fusions associated with tumor progression.

Clin Cancer Res. 2018 Mar 19;:

Authors: Keysar S, Eagles J, Miller B, Jackson BC, Chowdhury FN, Reisinger J, Chimed TS, Le PN, Morton JJ, Somerset H, Varella-Garcia M, Tan AC, Song JI, Bowles DW, Reyland ME, Jimeno A

Abstract
PURPOSE: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells.
EXPERIMENTAL DESIGN: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient. Patient and PDX samples were analyzed by RNA-seq and Exome-seq. Sphere formation potential and in vivo tumorigenicity was assessed by sorting for Aldefluor (ALDH) activity and CD44 expressing subpopulations.
RESULTS: For successive MEC relapses we found a time-dependent increase in CSCs (ALDH+CD44high), increasing from 0.2% to 4.5% (P=0.033), but more importantly we observed an increase in individual CSC sphere formation and tumorigenic potential. A 50% increase in mutational burden was documented in subsequent MEC tumors, and this was associated with increased expression of tumor promoting genes (MT1E, LGR5, LEF1), decreased expression of tumor suppressor genes (CDKN2B, SIK1, TP53), and higher expression of CSC-related proteins such as SOX2, MYC, and ALDH1A1. Finally, genomic analyses identified a novel NFIB-MTFR2 fusion in an ACC tumor and confirmed previously reported fusions (NTRK3-ETV6 and MYB-NFIB).
CONCLUSIONS: Sequential MEC PDX models preserved key patient features and enabled the identification of genetic events putatively contributing to increases in both CSC proportion and intrinsic tumorigenicity, which mirrored the patient's clinical course.

PMID: 29555661 [PubMed - as supplied by publisher]

Serum levels of selected adipocytokines in benign and malignant parotid gland tumor patients.

Fetched: March 21st, 2018, 5:00am GMT

Serum levels of selected adipocytokines in benign and malignant parotid gland tumor patients.

Cytokine. 2018 Mar 14;106:40-44

Authors: Sowa P, Misiolek M, Orecka B, Czecior E, Adamczyk-Sowa M

Abstract
OBJECTIVES: The aim of this study was to evaluate serum levels of adiponectin, leptin, visfatin and IL-6 in patients with pleomorphic adenoma, Warthin's tumor and acinic cell carcinoma of the parotid gland.
MATERIALS AND METHODS: Venous blood samples were collected from 30 patients with pleomorphic adenoma, 21 patients with Warthin's tumor and 8 patients with acinic cell carcinoma. Serum adiponectin, leptin, visfatin, IL-6 and CRP concentrations were determined.
RESULTS: Our results revealed significantly lower adiponectin serum levels in patients with malignant tumors compared to benign tumor individuals. Moreover, in benign cases the level was significantly higher compared to controls. Furthermore, serum leptin concentrations of benign tumor patients were higher compared to controls. Those differences, however, were observed only in males. The serum visfatin level was elevated in all tumor subjects compared to healthy individuals, whereas the serum IL-6 concentration was similar.
CONCLUSIONS: We anticipate that adiponectin may play a potential protective role in salivary gland tumors. Also leptin and visfatin seem to play an important role in salivary gland tumor pathology, although in males and females leptin may act or be regulated in a different manner. The influence of visfatin on salivary gland tumors is probably independent of IL-6 production.

PMID: 29549722 [PubMed - as supplied by publisher]

Atypical flat lesions derive from pancreatic acinar cells.

Fetched: March 21st, 2018, 5:00am GMT

Atypical flat lesions derive from pancreatic acinar cells.

Pancreatology. 2017 May - Jun;17(3):350-353

Authors: von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I

PMID: 28473229 [PubMed - indexed for MEDLINE]

Pancreatic panniculitis as a presentation symptom of acinar cell carcinoma.

Fetched: March 14th, 2018, 5:00am GMT

Pancreatic panniculitis as a presentation symptom of acinar cell carcinoma.

Rev Esp Enferm Dig. 2018 Mar 12;110:

Authors: de Frutos Rosa D, Espinosa Taranilla L, González de Canales de Simón P, Vélez Velázquez MD, Guirado Koch C

PMID: 29527901 [PubMed - as supplied by publisher]

The anteroposterior diameter of nodules in the risk assessment of papillary thyroid microcarcinoma.

Fetched: March 10th, 2018, 5:00am GMT

The anteroposterior diameter of nodules in the risk assessment of papillary thyroid microcarcinoma.

Medicine (Baltimore). 2018 Mar;97(10):e9712

Authors: Huang K, Gao N, Zhai Q, Bian D, Wang D, Wang X

PMID: 29517693 [PubMed - in process]

BRAF gene rearrangements can be identified by FISH studies in pancreatic acinar cell carcinoma.

Fetched: March 8th, 2018, 5:00am GMT

BRAF gene rearrangements can be identified by FISH studies in pancreatic acinar cell carcinoma.

Pathology. 2018 Mar 02;:

Authors: Chou A, Kim Y, Samra JS, Pajic M, Gill AJ

PMID: 29506751 [PubMed - as supplied by publisher]

REASONS TO RUN - Cape Cod Times

Posted: March 17th, 2018, 6:53pm GMT

Cape Cod Times

REASONS TO RUN
Cape Cod Times
Massachusetts General Hospital saved his life twice, in 2009 and 2015, by treating his rare form of cancer — adenoid cystic carcinoma — with an advanced and rare treatment known as proton beam therapy, O'Connell said. For scheduling reasons, O ...

In the fight for her life, young professional runner isn't slowing down - KSL.com

Posted: March 17th, 2018, 12:53am GMT

KSL.com

In the fight for her life, young professional runner isn't slowing down
KSL.com
On the phone, the doctor told Grunewald the name of her cancer: adenoid cystic carcinoma. She'd never heard of it, so she googled it. It wasn't very promising. "I saw that there aren't any treatments for it," she said. "I just saw that it was a rare ...

and more »

In the fight for her life, young professional runner isn't slowing down - WTVA

Posted: March 16th, 2018, 1:32am GMT

In the fight for her life, young professional runner isn't slowing down
WTVA
While waiting for the results, she traveled with her team to Arizona State University, ready to open her season with the 1500 meters, her premier event. In the lobby of the hotel, she got the call. "I remember very few things about the phone call ...

Gongwin announces trials for liver cancer treatment - Taipei Times

Posted: March 4th, 2018, 2:04pm GMT

Gongwin announces trials for liver cancer treatment
Taipei Times
PTS100 is designed to fill the gap for liver cancer patients who have exhausted first-line treatment options, but whose conditions do not yet warrant targeted therapy, the company said. Looking ahead, it expects to gain marketing approval in China for ...

Systemic therapy in non-conventional cancers of the larynx.

Fetched: June 20th, 2018, 5:00am GMT

Systemic therapy in non-conventional cancers of the larynx.

Oral Oncol. 2018 Jul;82:61-68

Authors: Tan E, Mody MD, Saba NF

PMID: 29909903 [PubMed - in process]

Salivary gland tumors in Veracruz. Experience of two institutions

Fetched: June 16th, 2018, 5:00am GMT

Salivary gland tumors in Veracruz. Experience of two institutions

Rev Med Inst Mex Seguro Soc. 2018 Mar-Apr;56(2):148-153

Authors: Sotelo-Gavito JJ, Pérez-Montaño M, Alderete-Vázquez G, Capetillo-Hernández G, Grube-Pagola P

Abstract
Background: The aim of this paper was to know the epidemiological characteristics of the salivary gland tumors in a Mexican population.
Methods: A descriptive, retrospective and cross-sectional study was performed. All cases of salivary gland tumor were collected in a period of 5 years (2009-2014) in two hospitals of our State, the Hospital General de Veracruz and the Unidad Médica de Alta Especialidad y Hospital de Especialidades No. 14, with the study of variables like: age, gender, location, biological behavior and histological type. The series studied included a total of 79 cases.
Results: 51% (40 cases) corresponded to female patients, the average age was 52.13 years (range of 14 to 87 years). The most frequent location of neoplasia was in the parotid gland (72%). The most frequent benign neoplasms were the pleomorphic adenoma and Warthin's tumor. The most frequent malignancy was cystic adenoid carcinoma, followed by moderately differentiated carcinoma.
Conclusions: Our results are similar to those previously reported in Mexico. The main neoplasms were the pleomorphic adenoma as a benign tumor and as malignant tumors the adenoid cystic carcinoma and the moderately differentiated carcinoma.

PMID: 29901947 [PubMed - in process]

Dedifferentiated adenoid cystic carcinoma ex pleomorphic adenoma of the parotid.

Fetched: June 14th, 2018, 5:00am GMT

Dedifferentiated adenoid cystic carcinoma ex pleomorphic adenoma of the parotid.

J Cancer Res Ther. 2018 Apr-Jun;14(3):706-708

Authors: Bhardwaj M, Gupta P

Abstract
Carcinoma ex pleomorphic adenoma (Ca ex PA) is defined as a carcinoma arising from a primary (de novo) or recurrent benign pleomorphic adenoma. The most common histological subtype is adenocarcinoma, not otherwise specified, salivary duct carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma (ACC). Few case reports of de novo dedifferentiation in ACC are there in the literature, mostly involving minor salivary glands. The dedifferentiated adenoid cystic carcinoma arising in a pleomorphic adenoma of the parotid gland has not been reported earlier. The present case highlights this rare histological subtype seen in Ca ex PA and the role of extensive histopathological examination and immunohistochemistry.

PMID: 29893347 [PubMed - in process]

IGFBP2 promotes salivary adenoid cystic carcinoma metastasis by activating the NF-κB/ZEB1 signaling pathway.

Fetched: June 11th, 2018, 5:00am GMT

IGFBP2 promotes salivary adenoid cystic carcinoma metastasis by activating the NF-κB/ZEB1 signaling pathway.

Cancer Lett. 2018 Jun 06;:

Authors: Yao X, Wang Y, Duan Y, Zhang Q, Li P, Jin R, Tao Y, Zhang W, Wang X, Jing C, Zhou X

Abstract
Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

PMID: 29885520 [PubMed - as supplied by publisher]

Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

Fetched: June 8th, 2018, 5:00am GMT

Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

Biochem Biophys Rep. 2018 Jul;14:64-68

Authors: Yamada S, Itai S, Nakamura T, Yanaka M, Kaneko MK, Kato Y

Abstract
CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C44Mab-5 (IgG1, kappa), recognized both CD44s and CD44v3-10. C44Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C44Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C44Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

PMID: 29872736 [PubMed]

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

Fetched: June 7th, 2018, 5:00am GMT

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

Eur J Cancer. 2018 Jun 02;98:48-58

Authors: Mills MN, Yang GQ, Oliver DE, Liveringhouse CL, Ahmed KA, Orman AG, Laronga C, Hoover SJ, Khakpour N, Costa RLB, Diaz R

Abstract
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.
METHODS: A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.
RESULTS: MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC.
CONCLUSION(S): Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments.

PMID: 29870876 [PubMed - as supplied by publisher]

A Comparative Study of Primary Adenoid Cystic and Mucoepidermoid Carcinoma of Lung.

Fetched: June 7th, 2018, 5:00am GMT

A Comparative Study of Primary Adenoid Cystic and Mucoepidermoid Carcinoma of Lung.

Front Oncol. 2018;8:153

Authors: Kumar V, Soni P, Garg M, Goyal A, Meghal T, Kamholz S, Chandra AB

Abstract
Background: Pulmonary mucoepidermoid carcinoma (PMEC) and pulmonary adenoid cystic carcinoma (PACC) are the two major types of primary salivary gland-type (PSGT) lung cancers. The demographic profile, clinicopathological features, and predictors of survival as an overall group have not been described for PSGT cancers of lung.
Methods: In this study, we analyzed demographic, clinical, and survival data from 1,032 patients (546 PMEC and 486 PACC) who were diagnosed of PSGT lung cancer in the Surveillance, Epidemiology and End Results database from 1973 to 2014.
Results: The PSGT constituted 0.09% of all lung cancers with age-adjusted incidence rate of 0.07 per 100,000 person-years and change of -32% from 1973 to 2014. The incidence of PMEC was slightly higher than PACC but there were no differences in the age and sex distribution. PACCs (55%) were significantly higher at trachea and main bronchus while PMECs were more common at peripheral lungs (85%). Most of the tumors were diagnosed at an early stage and were low grade irrespective of histology. As compared to PMEC, significantly higher number of patients with PACC underwent radical surgery and received adjuvant radiation. The 1- and 5-year cause-specific survival was 76.6 and 62.8%, respectively. On multivariate analysis, the survival was affected by age at diagnosis, tumor stage, histological grade, period of diagnosis, and surgical resection. The histology showed strong interaction with time and hazard ratio of patients with PACC was significantly worse than patients with PMEC only after 5 years.
Conclusion: The incidence of pulmonary PSGT cancer is 7 cases per 10 million population in the United States and is decreasing. There was no difference between demographic profile of patients with PMEC and PACC but pathological features were diverse. The difference in the survival of patients with the two histological types surfaced only after 5 years when survival of patients with PMEC was better than PACC.

PMID: 29868475 [PubMed]

Immunohistochemical Expression of CD-117 (c-KIT), P-53 and Ki-67 in Adenoid Cystic Carcinoma of Palate.

Fetched: June 7th, 2018, 5:00am GMT

Immunohistochemical Expression of CD-117 (c-KIT), P-53 and Ki-67 in Adenoid Cystic Carcinoma of Palate.

J Coll Physicians Surg Pak. 2018 Jun;28(6):S130-S132

Authors: Bajpai M, Pardhe N

Abstract
Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary glands characterized histopathologically by biphasic epithelial tumor comprised of myoepithelial and ductal cells. There is a paucity of the literature regarding the immunohistochemical labelling of ACC arising in minor salivary glands. This paper reports an additional case of palatal ACC with an emphasis on its immunohistochemical staining using three different markers. Immunohistochemistry allows a better differentiation of ACC with its closest imitators, like polymorphous low grade adenocarcinoma (PLGA), considering that the latter is lesser aggressive and demands a lesser aggressive treatment approach.

PMID: 29866247 [PubMed - in process]

Management of Skull Base Tumors in the Obstetric Population: A Case Series.

Fetched: June 7th, 2018, 5:00am GMT

Management of Skull Base Tumors in the Obstetric Population: A Case Series.

World Neurosurg. 2018 May;113:e373-e382

Authors: Priddy BH, Otto BA, Carrau RL, Prevedello DM

Abstract
BACKGROUND: Neoplasms rarely present during pregnancy; however, increases in plasma volume, hormone release-induced growth, and tumor hypervascularity can cause rapidly progressive symptoms of varying severity, ranging from those not requiring intervention to those necessitating emergent operations. Here we describe an algorithm for the management of symptomatic neoplasms in the obstetric population and provide recommendations for surgical indications and timing.
METHODS: Patients who presented to the skull base clinic at a large tertiary care hospital between 2010 and 2016 were reviewed to identify those who presented with a skull base tumor during pregnancy.
RESULTS: Our study cohort comprised 9 women with a skull base tumor during pregnancy. Four patients presented with symptoms that necessitated emergent skull base surgery, and 5 underwent surgery after delivery or were followed with continued surveillance. All operated patients had a World Health Organization grade I or II meningioma or schwannoma. There were no maternal complications. Based on our experience with this cohort, we have created a management algorithm.
CONCLUSIONS: Management of a symptomatic tumor during pregnancy requires balancing the potential for curing the mother and the risk of harming the fetus. Trimester of pregnancy is the most critical factor in evaluating the need for urgent management. The second trimester is the optimal time for surgery, associated with the lowest risk for spontaneous abortion or preterm birth. The first and third trimesters are associated with increased risk of miscarriage and preterm labor, respectively. Induction of labor for preterm delivery, followed by surgery, may be appropriate in the early third trimester. Regardless of the perceived risk, however, all pregnant women with an emergent presentation should be offered surgery, regardless of trimester.

PMID: 29454125 [PubMed - indexed for MEDLINE]

Alterations of Notch pathway in patients with adenoid cystic carcinoma of the trachea and its impact on survival.

Fetched: June 5th, 2018, 5:00am GMT

Alterations of Notch pathway in patients with adenoid cystic carcinoma of the trachea and its impact on survival.

Lung Cancer. 2018 Jul;121:41-47

Authors: Xie M, Wei S, Wu X, Li X, You Y, He C

Abstract
INTRODUCTION: Adenoid cystic carcinoma (ACC) of the trachea lacks of well-characterized molecular markers. There is currently no specific treatment for metastatic ACC of the trachea. This study aimed to identify genomic mutations of Notch pathway and investigate the efficacy of NOTCH inhibitor in ACC of the trachea.
METHODS: 73 Patients with ACC of the trachea at four institutions from 2008 to 2016 were identified. Analysis of hotspot mutations in cancer-related genes of Notch pathway was performed using next generation sequencing. Gene-expression and functional analyses were performed to study the mechanism of activation through mutation. Univariable and multivariable Cox regression models were used to predict overall survival (OS). Patient-derived xenograft (PDX) models were established and treated with NOTCH inhibitor Brontictuzumab.
RESULTS: Gain-of-function mutations of the NOTCH1 gene occurred in 12 (16.4%) tumors, leading to stabilization of the intracellular cleaved form of NOTCH1 (ICN1). NOTCH1 mutation was associated with increased NOTCH1 activation and its target gene HES1. Mutations in NOTCH2 (3/73), NOTCH4 (2/73), JAG1 (1/73) and FBXW7 (2/73) were also identified in 8 (11.0%) patients. A strong inverse correlation of expression was observed between FBXW7 and HES1. NOTCH1 mutation was associated with solid subtype (P = 0.02), younger age at diagnosis (P = 0.041) and shorter overall survival (OS) (P = 0.017). NOTCH1 mutation was not an independent prognostic factor in the presence of histologic subtype and resection margin. Brontictuzumab significantly reduced tumor growth in NOTCH1-mutated PDX.
CONCLUSION: NOTCH1 mutation is associated with activation of Notch pathway in ACC of the trachea. NOTCH1 is a potential target for therapeutic intervention in patients with ACC of the trachea.

PMID: 29858025 [PubMed - in process]

Accessory lacrimal gland tumours of the eye region.

Fetched: June 3rd, 2018, 5:00am GMT

Accessory lacrimal gland tumours of the eye region.

Acta Ophthalmol. 2018 May 31;:

Authors: Mulay K, Rasmussen PK, Aggarwal E, Honavar SG, Heegaard S

Abstract
PURPOSE: Tumours of the accessory lacrimal glands (ALGs) are rare and need to be differentiated from other tumours involving the eyelids and caruncle. We report on a consecutive series of patients with ALG tumours and describe the clinical characteristics.
METHODS: A retrospective case series including all patients who were operated for ALG tumours at two different centres.
RESULTS: The study included 27 patients diagnosed with ALG tumours. Mean age at presentation was 55.9 years (range, 24-81 years; median, 56 years). Overall, a slight male preponderance was observed (M:F = 1.4:1). Histologically, pleomorphic adenoma was the commonest diagnosis (24 of 27; 88.9%), followed by adenoid cystic carcinoma (2 of 27; 7.4%) and oncocytoma (one of 27; 3.7%). A complete surgical excision was curative in all patients.
CONCLUSION: Accessory lacrimal gland (ALG) tumours are rare and may therefore pose diagnostic difficulties for clinicians. Histopathological examination of these tumours is the cornerstone of the diagnostic evaluation. Complete surgical excision is the treatment of choice in these tumours.

PMID: 29855174 [PubMed - as supplied by publisher]

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