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Pancreatic adenocarcinoma

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https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#1
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811947/solitary-skull-metastasis-as-the-first-presentation-of-a-metachronous-primary-lung-cancer-in-a-survivor-from-pancreatic-cancer
#2
Ali Altalhy, Yazid Maghrabi, Zuhoor Almansouri, Saleh S Baeesa
Skull metastasis from lung cancer is relatively common, yet the first presentation for this malignant disease is a rare occurrence. We herein report a case of a 54-year-old female, who had a good outcome following Whipple procedure for periampullary adenocarcinoma five years before her current presentation. During a routine follow-up, she was found to have a slowly progressive painless right parietal swelling. The systemic screening workup revealed no abdominal disease, but a solitary pulmonary nodule was identified...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28811674/regenerative-medicine-and-cell-based-approaches-to-restore-pancreatic-function
#3
REVIEW
Cara Ellis, Adam Ramzy, Timothy J Kieffer
The pancreas is a complex organ with exocrine and endocrine components. Many pathologies impair exocrine function, including chronic pancreatitis, cystic fibrosis and pancreatic ductal adenocarcinoma. Conversely, when the endocrine pancreas fails to secrete sufficient insulin, patients develop diabetes mellitus. Pathology in either the endocrine or exocrine pancreas results in devastating economic and personal consequences. The current standard therapy for treating patients with type 1 diabetes mellitus is daily exogenous insulin injections, but cell sources of insulin provide superior glycaemic regulation and research is now focused on the goal of regenerating or replacing β cells...
August 16, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#4
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#5
(no author information available yet)
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28808501/evolving-treatment-landscape-for-early-and-advanced-pancreatic-cancer
#6
REVIEW
Sally C Lau, Winson Y Cheung
Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multi-agent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving...
July 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28808290/molecular-mr-imaging-of-fibrosis-in-a-mouse-model-of-pancreatic-cancer
#7
Miloslav Polasek, Yan Yang, Daniel T Schühle, Mohammad A Yaseen, Young R Kim, Yu Sub Sung, Alexander R Guimaraes, Peter Caravan
Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#8
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28807830/usp5-promotes-tumorigenesis-and-progression-of-pancreatic-cancer-by-stabilizing-foxm1-protein
#9
Xin-Yan Li, Hai-Yun Wu, Xiao-Fang Mao, Li-Xin Jiang, Yong-Xiang Wang
Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including glioblastoma, melanoma and hepatocellular carcinoma. However, the role of USP5 in tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) has not been studied yet. In this study, we demonstrated that USP5 was significantly upregulated in a panel of PDAC cell lines and correlated with FoxM1 protein expression. USP5 knockdown inhibited proliferation of PANC-1 and SW1990, two PDAC cell lines. In the mouse xenografted pancreatic tumor model, suppression of USP5 significantly decreased tumor growth, correlated with down regulation of FoxM1...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807337/evaluation-of-cd43-expression-in-non-hematopoietic-malignancies
#10
Bjorn H Batdorf, Steven H Kroft, Paul R Hosking, Alexandra M Harrington, Alexander C Mackinnon, Horatiu Olteanu
OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28803860/intestinal-permeability-changes-systemic-endotoxemia-inflammatory-serum-markers-and-sepsis-after-whipple-s-operation-for-carcinoma-of-the-pancreas-head
#11
Mario Schietroma, Beatrice Pessia, Francesco Carlei, Gianfranco Amicucci
POURPOSE: The aim was to evaluate the relationship between failure of gut barrier function, inflammatory markers and septic complications after pancreatoduodenectomy for pancreatic adenocarcinoma. METHODOLOGY: 44 patients were enrolled in this prospective observational clinical study and underwent curative open pancreatoduodenectomy for adenocarcinoma of the head of the pancreas. All patients underwent assessment of intestinal permeability using the lactulose/manitol excretions ratios (L/M ratio), endotoxemia, IL-1β, IL-6, CRP, and elastase levels before surgery and on postoperative days 1, 3 and 7...
July 29, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#12
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
July 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803603/prognostic-impact-of-cell-division-cycle-associated-2-expression-on-pancreatic-ductal-adenocarcinoma
#13
Meng-Yi Wang, Zhe-Yu Niu, Xiang-Gao Gao, Li Zhou, Quan Liao, Yu-Pei Zhao
Objective To examine the expression of cell division cycle associated 2 (CDCA 2) in pancreatic ductal adenocarcinoma (PDAC) and investigate its role in prognosis of PDAC patients. Methods This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up. Clinicopathologic data were collected through clinical database. Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues...
September 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28803454/serum-carbohydrate-antigen-19-9-in-pancreatic-adenocarcinoma-a-mini-review-for-surgeons
#14
REVIEW
Su Kah Goh, Grace Gold, Christopher Christophi, Vijayaragavan Muralidharan
The optimal management of oncological conditions is reflected by the careful interpretation of investigations for screening, diagnosis, staging, prognostication and surveillance. Serum tumour markers are examples of commonly requested tests in conjunction with other imaging and endoscopic tests that are used to help clinicians to stratify therapeutic decisions. Serum carbohydrate antigen 19-9 (CA19-9) is a key biomarker for pancreatic cancers. Although this biomarker is considered clinically useful and informative, clinicians are often challenged by the accurate interpretation of elevated serum CA19-9 levels...
August 13, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28802189/pt-but-not-pn-stage-of-the-8th-tnm-classification-significantly-improves-prognostication-in-pancreatic-ductal-adenocarcinoma
#15
Anna Melissa Schlitter, Moritz Jesinghaus, Carsten Jäger, Björn Konukiewitz, Alexander Muckenhuber, Ihsan Ekin Demir, Marcus Bahra, Carsten Denkert, Helmut Friess, Günter Kloeppel, Güralp O Ceyhan, Wilko Weichert
The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients...
August 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#16
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795470/dmkn-contributes-to-the-epithelial-mesenchymal-transition-through-increased-activation-of-stat3-in-pancreatic-cancer
#17
Chaohao Huang, Yukai Xiang, Shengchuan Chen, Huajun Yu, Zhengde Wen, Tingting Ye, Hongwei Sun, Hongru Kong, Dapei Li, Dinglai Yu, Bicheng Chen, Mengtao Zhou
DMKN was first identified in relation to skin lesion healing and skin carcinoma. Recently, its expression has been associated with pancreatic cancer tumorigenesis, although its involvement remains poorly understood. Herein, we show that DMKN loss of function in Patu-8988 and PANC-1 pancreatic cancer cell lines results in reduced phosphorylation of signal transducer and activator of transcription-3 (STAT3), and increased activation of extracellular signal-regulated kinase (ERK1/2) and AKT serine/threonine kinase...
August 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28794500/para-aortic-lymph-node-metastases-in-pancreatic-cancer-should-not-be-considered-a-watershed-for-curative-resection
#18
Sebastian Hempel, Verena Plodeck, Franz Mierke, Marius Distler, Daniela E Aust, Hans-Detlev Saeger, Jürgen Weitz, Thilo Welsch
No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005-2015. In 95 cases, the PALN were separately labelled and histopathologically analysed. Metastatic PALN (PALN+) were found in 14.7% (14/95). PALN+ stage was associated with increased regional lymph node metastasis...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793134/clinical-and-genetic-implications-of-dna-mismatch-repair-deficiency-in-patients-with-pancreatic-ductal-adenocarcinoma
#19
Jordan M Cloyd, Matthew H G Katz, Huamin Wang, Amanda Cuddy, Y Nancy You
No abstract text is available yet for this article.
August 9, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28790064/atm-deficiency-generating-genomic-instability-sensitizes-pancreatic-ductal-adenocarcinoma-cells-to-therapy-induced-dna-damage
#20
Lukas Perkhofer, Anna Schmitt, Maria Carolina Romero Carrasco, Michaela Ihle, Stephanie Hampp, Dietrich Alexander Ruess, Elisabeth Hessmann, Ronan Russell, André Lechel, Ninel Azoitei, Qiong Lin, Stefan Liebau, Meike Hohwieler, Hanibal Bohnenberger, Marina Lesina, Hana Algül, Laura Gieldon, Evelin Schröck, Jochen Gaedcke, Martin Wagner, Lisa Wiesmüller, Bence Sipos, Thomas Seufferlein, Hans Christian Reinhardt, Pierre-Olivier Frappart, Alexander Kleger
Pancreatic adenocarcinomas (PDAC) harbour recurrent functional mutations of the master DNA damage response kinase ATM which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements and deregulated DNA integrity checkpoints, reminiscent of human PDAC...
August 8, 2017: Cancer Research
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