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Pancreatic ductal adenocarcinoma

Charline Ogier, Pierre-Emmanuel Colombo, Corinne Bousquet, Lucile Canterel-Thouennon, Pierre Sicard, Véronique Garambois, Gaëlle Thomas, Nadège Gaborit, Marta Jarlier, Nelly Pirot, Martine Pugnière, Nadia Vie, Céline Gongora, Pierre Martineau, Bruno Robert, André Pèlegrin, Thierry Chardès, Christel Larbouret
Neuregulin 1 (NRG1), a ligand for HER3 and HER4 receptors, is secreted by both pancreatic tumor cells (PC) and cancer-associated fibroblasts (CAFs), the latter representing the most abundant compound of pancreatic stroma. This desmoplastic stroma contributes to Pancreatic Ductal Adenocarcinoma (PDAC) aggressiveness and therapeutic failure by promoting tumor progression, invasion and resistance to chemotherapies. In the present work, we aimed at disrupting the complex crosstalk between PC and CAF in order to prevent tumor cell proliferation...
June 20, 2018: Cancer Letters
Bo Ram Kim, Jung Hoon Kim, Su Joa Ahn, Ijin Joo, Seo-Youn Choi, Sang Joon Park, Joon Koo Han
OBJECTIVES: To assess utility of CT findings and texture analysis for predicting the resectability and prognosis in patients after neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Among 308 patients, 45 with PDAC underwent neoadjuvant therapy (concurrent-chemoradiation-therapy, CCRT, n = 27 and chemotherapy, ChoT, n = 18) before surgery were included. All underwent baseline and preoperative CT. Two reviewers assessed CT findings and resectability...
June 21, 2018: European Radiology
Xudong Huang, Jian Zheng, Jun Li, Xu Che, Wenle Tan, Wen Tan, Mingming Shao, Xinxin Cheng, Zhongli Du, Yanjie Zhao, Chengfeng Wang, Chen Wu, Dongxin Lin
Genetic variation (rs372883C/T) in the 3'-untranslated region of BTB and CNC homology 1 ( BACH1 ) has been associated with pancreatic ductal adenocarcinoma (PDAC) risk in our previous genome-wide association study; however, the action roles of this genetic variation in PDAC remains unknown. Methods: BACH1 expression was measured by quantitative real-time PCR, Western blot and immunohistochemistry. The effects of BACH1 on cell proliferation and sensitivity to gemcitabine were examined by alteration of BACH1 expression in PDAC cells...
2018: Theranostics
Bing Liu, Max Heckler, Ulrike Heger, Susanne Roth, Ulla Klaiber, Markus W Büchler, Oliver Strobel, Christoph W Michalski, Thilo Hackert
BACKGROUND: The number of lymph nodes to be resected in surgery for non-pancreatic periampullary cancer remains unclear. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to gather information from a large retrospective cohort. To define a novel, reasonable cut-off associated with survival, we stratified patients into subgroups depending on the number of resected lymph nodes. RESULTS: 1481 nodal-negative patients resected for periampullary cancer (excluding pancreatic ductal adenocarcinoma) were included...
June 19, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Julian Burks, Sandeep Nadella, Abdullah Mahmud, Charoen Mankongpaisarnrung, Juan Wang, Jong-In Hahm, Robin D Tucker, Narayan Shivapurkar, Stephan T Stern, Jill P Smith
Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) remains the most aggressive malignancy with the lowest 5-year survival rate of all cancers in part owing to the lack of tumor-specific therapy and the rapid metastatic nature of this cancer. The gastrointestinal peptide gastrin is a trophic peptide that stimulates growth of PDAC in an autocrine fashion by interaction with the cholecystokinin receptor that is overexpressed in this malignancy. Methods: We developed a therapeutic novel polyplex nanoparticle (NP) that selectively targets the cholecystokinin receptor on PDAC...
2018: Cellular and Molecular Gastroenterology and Hepatology
Jun Chen, Hao Zhang, Jiansheng Luo, Xiaokang Wu, Xueming Li, Xinyi Zhao, Dongkai Zhou, Shian Yu
Pancreatic ductal adenocarcinoma (PDA) is a worldwide health problem. Early diagnosis and assessment may enhance the quality of life and survival of patients. The present study investigated the potential correlations between the gene and protein expression of laminin-332 (LM-332 or laminin-5) and clinicopathological factors as well as evaluating its influence on the survival of patients with PDA. The expression of LM-332 subunit mRNAs in pancreatic carcinoma specimens from 37 patients was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis...
July 2018: Oncology Letters
Manjusha Thakar, Yue Hu, Michael Morreale, Lane Lerner, Wan Ying Lin, Rupashree Sen, Yi Cai, Enusha Karunasena, Maya Thakar, Soren Saggi, Harold Keer, Nita Ahuja
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations...
2018: PloS One
Joseph J Otto, Crystal L Daniels, Lindsay N Schambeau, Brittany N Williams, Jana M Rocker, Lewis K Pannell
A promising approach capitalizing on the specific and highly sensitive characteristics of the body's own immune system is demonstrated in the context of revealing pancreatic ductal adenocarcinoma cancer (PDAC). IgA from a local biofluid called gastrointestinal lavage fluid (GLF) is used to investigate glycan reactivity to show the potential of this approach. IgA antibody responses, just as with IgG, result in amplification of a small signal which aids in detecting changes from a healthy state. IgA from GLF was screened against glycan arrays containing 609 glycan structures to investigate differential binding patterns associated with the disease...
June 2018: Glycoconjugate Journal
Laura V Danai, Ana Babic, Michael H Rosenthal, Emily A Dennstedt, Alexander Muir, Evan C Lien, Jared R Mayers, Karen Tai, Allison N Lau, Paul Jones-Sali, Carla M Prado, Gloria M Petersen, Naoki Takahashi, Motokazu Sugimoto, Jen Jen Yeh, Nicole Lopez, Nabeel Bardeesy, Carlos Fernandez-Del Castillo, Andrew S Liss, Albert C Koong, Justin Bui, Chen Yuan, Marisa W Welch, Lauren K Brais, Matthew H Kulke, Courtney Dennis, Clary B Clish, Brian M Wolpin, Matthew G Vander Heiden
Malignancy is accompanied by changes in the metabolism of both cells and the organism1,2 . Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer3,4 . Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic5,6 . Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer...
June 20, 2018: Nature
Petra Radulović, Božo Krušlin
Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin...
June 20, 2018: Bosnian Journal of Basic Medical Sciences
Yingcheng Wu, Jinhuan Wei, Yue Ming, Zhanghao Chen, Jinzhong Yu, Renfang Mao, Hao Chen, Guoxiong Zhou, Yihui Fan
The low survival of patients with pancreatic ductal adenocarcinoma (PDAC) makes the treatment of this disease one of the most challenging task in modern medicine. Here, by mining a large-scale cancer genome atlas data set of pancreatic cancer tissues, we identified 21 long noncoding RNAs (lncRNAs) that significantly associated with overall survival in patients with PDAC (P < .01). Further analysis revealed that 8 lncRNAs turned out to be independently correlated with patients' overall survival, and the risk score could be calculated based on their expression...
June 20, 2018: Journal of Cellular Biochemistry
Sapna Syngal, C Sloane Furniss
No abstract text is available yet for this article.
June 19, 2018: JAMA: the Journal of the American Medical Association
Feng Shao, Mei Huang, Futao Meng, Qiang Huang
Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR) cell lines and compared the circular RNAs (circRNAs) profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Differentially expressed circRNAs were demonstrated using scatter plot and cluster heatmap analysis...
2018: Frontiers in Pharmacology
Xinlu Liu, Yejing Weng, Peng Liu, Zhigang Sui, Lei Zhou, Yinpeng Huang, Lihua Zhang, Yukui Zhang, Xiaodong Tan
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal cancer characterized by an extremely low survival rate because of early metastasis. Identifying satisfactory therapeutic targets associated with metastasis is crucial to improve the treatment effect of PDAC. Materials and methods: In this research, we used stable isotope labeling by amino acids in cell culture, 1-dodecyl-3-methylimidazolium chloride-assisted sample preparation method preparing protein sample and nano-reversed-phase liquid chromatography-mass spectrometry/mass spectrometry analysis to perform the comparative proteomics of two homologous hamster pancreatic cancer cell lines that are different in metastatic ability: PC-1...
2018: OncoTargets and Therapy
Parash Parajuli, Santosh Kumar, Audrey Loumaye, Purba Singh, Sailaja Eragamreddy, Thien Ly Nguyen, Seval Ozkan, Mohammed S Razzaque, Céline Prunier, Jean-Paul Thissen, Azeddine Atfi
Cancer cachexia is characterized by extreme skeletal muscle loss that results in high morbidity and mortality. The incidence of cachexia varies among tumor types, being lowest in sarcomas, whereas 90% of pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss. How these tumors trigger muscle depletion is still unfolding. Serendipitously, we found that overexpression of Twist1 in mouse muscle progenitor cells, either constitutively during development or inducibly in adult animals, caused severe muscle atrophy with features reminiscent of cachexia...
June 18, 2018: Developmental Cell
Nicole M Aiello, Ravikanth Maddipati, Robert J Norgard, David Balli, Jinyang Li, Salina Yuan, Taiji Yamazoe, Taylor Black, Amine Sahmoud, Emma E Furth, Dafna Bar-Sagi, Ben Z Stanger
Epithelial-mesenchymal transition (EMT) is strongly implicated in tumor cell invasion and metastasis. EMT is thought to be regulated primarily at the transcriptional level through the repressive activity of EMT transcription factors. However, these classical mechanisms have been parsed out almost exclusively in vitro, leaving questions about the programs driving EMT in physiological contexts. Here, using a lineage-labeled mouse model of pancreatic ductal adenocarcinoma to study EMT in vivo, we found that most tumors lose their epithelial phenotype through an alternative program involving protein internalization rather than transcriptional repression, resulting in a "partial EMT" phenotype...
June 18, 2018: Developmental Cell
D Caputo, M Cartillone, C Cascone, D Pozzi, L Digiacomo, S Palchetti, G Caracciolo, R Coppola
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) early diagnosis is  crucial  and new, cheap and user-friendly techniques for biomarker identification  are  needed. "Protein corona" (PC) is emerging a new bio-interface potentially useful in tumor early diagnosis. In a previous investigation, we showed that relevant differences between the  protein patterns of  PCs formed on lipid NPs after exposure to PDAC and non-cancer plasma  samples exist. To extend that research, We performed this pilot study to investigate the effect of PDAC tumor size and distant metastases on PC composition...
June 12, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Shohei Kawashiro, Shigeru Yamada, Masahiko Okamoto, Tatsuya Ohno, Takashi Nakano, Makoto Shinoto, Yoshiyuki Shioyama, Kenji Nemoto, Yuka Isozaki, Hiroshi Tsuji, Tadashi Kamada
PURPOSE: The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Somala Mohammed, Jose E Mendez-Reyes, Amy McElhany, Daniel Gonzales-Luna, George Van Buren, Daniel S Bland, Nicole Villafane-Ferriol, Jeanne A Pierzynski, Charles A West, Eric J Silberfein, William E Fisher
BACKGROUND: Addition of en bloc segmental venous reconstruction (VR) to pancreaticoduodenectomy (PD) for venous involvement of pancreatic tumors increases the complexity of the operation and may increase complications. The long-term mesenteric venous patency rate and oncologic outcome has not been well defined. METHODS: Our prospective database was reviewed to assess 90-day postoperative outcomes for patients who underwent PD or PD + VR (September 2004-June 2016)...
August 2018: Journal of Surgical Research
Sodai Sakamoto, Yosuke Tsuruga, Yuki Fujii, Hiroki Shomura, Atsuo Hattori, Keizo Kazui
INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging. PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis...
June 4, 2018: International Journal of Surgery Case Reports
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