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https://www.readbyqxmd.com/read/28726808/prevalence-of-germ-line-mutations-in-cancer-genes-among-pancreatic-cancer-patients-with-a-positive-family-history
#1
Kari G Chaffee, Ann L Oberg, Robert R McWilliams, Neil Majithia, Brian A Allen, John Kidd, Nanda Singh, Anne-Renee Hartman, Richard J Wenstrup, Gloria M Petersen
PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history.MethodsWe sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for familial pancreatic cancer (FPC), while the remaining were familial, but not FPC...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28723668/a-rare-case-of-esophageal-metastasis-from-pancreatic-ductal-adenocarcinoma-a-case-report-and-literature-review
#2
Lauren M Rosati, Megan N Kummerlowe, Justin Poling, Amy Hacker-Prietz, Amol K Narang, Eun J Shin, Dung T Le, Elliot K Fishman, Ralph H Hruban, Stephen C Yang, Matthew J Weiss, Joseph M Herman
PURPOSE: We report a very unique case of an esophageal metastasis from a pancreatic ductal adenocarcinoma (PDAC) primary. METHODS: After obtaining consent from the patient, all relevant records of the case were obtained and retrospectively reviewed. RESULTS: At presentation, the patient was diagnosed with synchronous pancreatic and esophageal cancer. He received six months of neoadjuvant therapy including FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and stereotactic body radiation therapy (SBRT) to the pancreatic tumor followed by a combined pancreaticoduodenectomy and Ivor Lewis esophagectomy...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723647/set-contributes-to-the-epithelial-mesenchymal-transition-of-pancreatic-cancer
#3
Hardik R Mody, Sau Wai Hung, Kineta Naidu, Haesung Lee, Caitlin A Gilbert, Toan Thanh Hoang, Rakesh K Pathak, Radhika Manoharan, Shanmugam Muruganandan, Rajgopal Govindarajan
Pancreatic cancer has a devastating prognosis due to 80-90% of diagnostic cases occurring when metastasis has already presented. Activation of the epithelial-mesenchymal transition (EMT) is a prerequisite for metastasis because it allows for the dissemination of tumor cells to blood stream and secondary organs. Here, we sought to determine the role of SET oncoprotein, an endogenous inhibitor of PP2A, in EMT and pancreatic tumor progression. Among the two major isoforms of SET (isoform 1 and isoform 2), higher protein levels of SET isoform 2 were identified in aggressive pancreatic cancer cell lines...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723631/cbl-b-predicts-postoperative-survival-in-patients-with-resectable-pancreatic-ductal-adenocarcinoma
#4
Qian Dong, Yuteng Ma, Yao Zhang, Xiujuan Qu, Zhi Li, Yafei Qi, Yunpeng Liu, Ce Li, Kai Li, Xianghong Yang, Xiaofang Che
Casitas B-lineage lymphoma b (Cbl-b) is a ubiquitin-protein ligase and a signal transducing adaptor protein involved in immune regulation, and it may be involved in the development and progression of cancer. We investigated the association between Cbl-b expression and prognosis in patients with resectable pancreatic ductal adenocarcinoma (PDAC). The clinicopathological characteristics and survival data of 134 patients with surgery for PDAC between January 2009 and February 2012 were retrospectively evaluated, and Cbl-b expression was assayed by immunohistochemical staining...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722124/pancreatic-undifferentiated-carcinoma-with-osteoclast-like-giant-cells-is-genetically-similar-to-but-clinically-distinct-from-conventional-ductal-adenocarcinoma
#5
Claudio Luchini, Antonio Pea, Gemma Lionheart, Andrea Mafficini, Alessia Nottegar, Nicola Veronese, Peter Chianchiano, Lodewijk A A Brosens, Michaël Noë, G Johan A Offerhaus, Raluca Yonescu, Yi Ning, Giuseppe Malleo, Giulio Riva, Paola Piccoli, Ivana Cataldo, Paola Capelli, Giuseppe Zamboni, Aldo Scarpa, Laura D Wood
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGC, including the whole exome sequencing of 8 UCOGC. We observed that 60% of the UCOGC contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722109/genomic-signatures-of-adenosquamous-carcinoma-of-the-pancreas-pasc
#6
Yuan Fang, Zhe Su, Jing Xie, Ruidong Xue, Qi Ma, Yanmeng Li, Yifan Zhao, Zeshi Song, Xiongxiong Lu, Hongwei Li, Chenghong Peng, Bai Fan, Baiyong Shen
In pancreatic cancer (PC), adenosquamous carcinoma of the pancreas (PASC) containing both ductal adenocarcinoma and squamous carcinoma in the same tumor represents ~ 4% of the total incidence. To date, the genomic features of this mixed tumor are still unknown. We analyzed genomes of 17 PASCs and 34 ductal adenocarcinomas (PDACs), showing that PASC carried highly enriched TP53 mutations and 3p loss compared to PDAC. Furthermore, we uncovered that adenomatous and squamous components of PASC harbored comparable genomic alterations, suggesting that two cellular components are developed from the same progenitor cancer cells...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28720574/fructose-1-6-bisphosphatase-inhibits-erk-activation-and-bypasses-gemcitabine-resistance-in-pancreatic-cancer-by-blocking-iqgap1-mapk-interaction
#7
Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang
Dysregulation of the mitogen-activated protein kinase (MAPK) pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and extracellular signaling-regulated kinases (ERK). Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28718411/molecular-events-in-the-natural-history-of-pancreatic-cancer
#8
REVIEW
Leslie E Oldfield, Ashton A Connor, Steven Gallinger
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest epithelial malignancies. Improvements in our understanding of PDAC carcinogenesis will hopefully improve its detection, management, and outcomes, as has been achieved with other malignancies. Here we review the literature on the natural history of PDAC, including its cell of origin, the initiating somatic mutational events, pathways deranged in the mature tumor, its biological heterogeneity, and the relationship of the primary tumor with metastases...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718038/reappraisal-of-staging-laparoscopy-for-patients-with-pancreatic-adenocarcinoma-a-contemporary-analysis-of-1001-patients
#9
Zhi Ven Fong, Donna Marie L Alvino, Carlos Fernández-Del Castillo, Winta T Mehtsun, Ilaria Pergolini, Andrew L Warshaw, David C Chang, Keith D Lillemoe, Cristina R Ferrone
BACKGROUND: Recent advances in imaging and the increasing use of neoadjuvant therapy puts the contemporary utility of staging laparoscopy for patients with pancreatic adenocarcinoma (PDAC) into question. This study aimed to develop a prognostic score to optimize prevention of an unnecessary laparotomy and minimize the rate for unnecessary laparoscopy. METHODS: Clinicopathologic data were evaluated for all patients undergoing surgical intervention for PDAC between 2001 and 2015, who were stratified into group 1 (2001-2008) and group 2 (2009-2014)...
July 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28715356/a-mouse-model-for-pain-and-neuroplastic-changes-associated-with-pancreatic-ductal-adenocarcinoma
#10
Deepitha Selvaraj, Michael Hirth, Jagadeesh Gandla, Rohini Kuner
Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest human malignancies and is associated with excruciating pain, which is a serious complication and severely impacts the quality of life in patients. In human patients, poor survival prognosis is linked to remarkable remodeling of intrapancreatic nerves, which, in turn, is correlated to increased pain intensity. Understanding mechanisms underlying pain associated with PDAC has been hampered by the lack of animal models which replicate all germane aspects of the disease and importantly, enable analyses of pain associated with PDAC...
August 2017: Pain
https://www.readbyqxmd.com/read/28714519/circulating-regulatory-t-cell-subsets-predict-overall-survival-of-patients-with-unresectable-pancreatic-cancer
#11
Chen Liu, He Cheng, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Quanxing Ni, Xianjun Yu
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28710540/home-based-exercise-during-preoperative-therapy-for-pancreatic-cancer
#12
An Ngo-Huang, Nathan H Parker, Xuemei Wang, Maria Q B Petzel, David Fogelman, Keri L Schadler, Eduardo Bruera, Jason B Fleming, Jeffrey E Lee, Matthew H G Katz
PURPOSE: Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy. METHODS: Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled...
July 15, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28709465/subclinical-focal-cholangitis-mimicking-liver-metastasis-in-asymptomatic-patients-with-history-of-pancreatic-ductal-adenocarcinoma-and-biliary-tree-intervention
#13
Natally Horvat, Edmund M Godfrey, Timothy J Sadler, Jaclyn F Hechtman, Laura H Tang, Carlie S Sigel, Serena Monti, Lorenzo Mannelli
BACKGROUND: Cholangitis is an inflammatory process of the biliary tract with a wide range of clinical manifestations and it is not always considered in the differential diagnosis in asymptomatic patients. To the best of our knowledge there is no previous report in the English literature of focal cholangitis manifesting exclusively as liver parenchymal changes mimicking liver metastasis in asymptomatic patients with pancreatic ductal adenocarcinoma (PDAC) and history of manipulation of the biliary tree...
July 14, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28705806/roles-of-autophagy-and-metabolism-in-pancreatic-cancer-cell-adaptation-to-environmental-challenges
#14
Sandrina Maertin, Jason M Elperin, Ethan Lotshaw, Matthias Sendler, Steven D Speakman, Kazuki Takakura, Benjamin M Reicher, Olga A Mareninova, Paul J Grippo, Julia Mayerle, Markus M Lerch, Anna S Gukovskaya
Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mTOR...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705007/pancreas-adenocarcinoma-novel-therapeutics
#15
Benjamin A Krantz, Kenneth H Yu, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is the third highest cause of cancer-related deaths in the US, and is projected to be second only to non-small cell lung cancer (NSCLC) by the 2020s. Current therapies have a modest impact on survival and median overall survival (mOS) across all stages of disease remains under a year. Over the last decade, however, great strides have been made in the understanding of PDAC pathobiology including the role of the tumor microenvironment (TME), DNA damage repair and mechanism of immunosuppression...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28705002/preclinical-models-of-pancreatic-ductal-adenocarcinoma
#16
Benjamin D Krempley, Kenneth H Yu
Unlike many other cancers, pancreatic ductal adenocarcinoma (PDAC) has seen only incremental improvement in mortality despite significant advances in our understanding of the underlying biology. A primary obstacle to progress has been our inability to properly model PDAC in a preclinical setting. PDAC is difficult to study because of its genetic heterogeneity, intricate stromal microenvironment, and complex interplay with our immune system. Finding a model that properly accounts for all these criteria remains difficult...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28703890/targeted-therapies-in-pancreatic-cancer-promises-and-failures
#17
Matineh Barati Bagherabad, Fahimeh Afzaljavan, Soodabeh ShahidSales, Seyed Mahdi Hassanian, Amir Avan
Pancreatic ductal adenocarcinoma (PDAC) is an incidence rate nearly equal to its mortality rate. The poor prognosis of the disease can be explained by the absence of effective biomarkers for screening and early detection, together with the aggressive behavior and resistance to the currently available chemotherapy. The therapeutic failure can also be attributed to the inter-/intra- tumor genetic heterogeneity and the abundance of tumor stroma that occupies the majority of the tumor mass. Gemcitabine is used in the treatment of PDAC, however, the response rate is less than 12%...
July 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28702661/clinically-approved-pegylated-nanoparticles-are-covered-by-a-protein-corona-that-boosts-the-uptake-by-cancer-cells
#18
M Papi, D Caputo, V Palmieri, R Coppola, S Palchetti, F Bugli, C Martini, L Digiacomo, D Pozzi, G Caracciolo
Today, liposomes are an advanced technology of drug carriers with a dozen drugs in clinical practice and many more in clinical trials. A bottleneck associated with the clinical translation of liposomes has long been 'opsonization', i.e. the adsorption of plasma proteins at the liposome surface resulting in their rapid clearance from circulation. For decades, the most popular way to avoid opsonization has been grafting polyethylene glycol (PEG) onto the liposome surface. Recent studies have clarified that grafting PEG onto the liposome surface reduces, but does not completely prevent protein binding...
July 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28701723/the-lncrna-malat1-acts-as-a-competing-endogenous-rna-to-regulate-kras-expression-by-sponging-mir-217-in-pancreatic-ductal-adenocarcinoma
#19
Pingping Liu, Haiyan Yang, Jing Zhang, Xiaozhong Peng, Zhaohui Lu, Weimin Tong, Jie Chen
The long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) has been shown to play an important role in tumourigenesis. The aim of this study was to investigate the role of MALAT1 in pancreatic ductal adenocarcinoma. MALAT1 is expressed at higher levels in pancreatic ductal adenocarcinoma (PDAC) tissues than in nontumour tissues and in metastatic PDAC than in localized tumours. Patients with PDAC and high MALAT1 expression levels have shorter overall survival than patients with PDAC and low MALAT1 expression levels...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701476/detection-of-early-pancreatic-ductal-adenocarcinoma-with-thrombospondin-2-and-ca19-9-blood-markers
#20
Jungsun Kim, William R Bamlet, Ann L Oberg, Kari G Chaffee, Greg Donahue, Xing-Jun Cao, Suresh Chari, Benjamin A Garcia, Gloria M Petersen, Kenneth S Zaret
Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls...
July 12, 2017: Science Translational Medicine
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