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Pancreatic ductal adenocarcinoma

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https://www.readbyqxmd.com/read/28817822/predictors-of-postoperative-non-chylous-massive-discharge-after-pancreaticoduodenectomy-for-pancreatic-ductal-adenocarcinoma
#1
Kyoji Ito, Yoshikuni Kawaguchi, Yoshihiro Sakamoto, Junichi Arita, Kiyoshi Hasegawa, Norihiro Kokudo
BACKGROUND: Pancreaticoduodenectomy (PD) is performed for pancreatic ductal adenocarcinoma (PDA) located at the pancreas head/body. Non-chylous massive discharge after PD is frequently encountered and can cause a vicious cycle of complications associated with severe dehydration and protein loss. METHODS: From August 2008 to June 2015, 102 patients who underwent PD for PDA were retrospectively reviewed. High non-chylous discharge was defined as postoperative daily serous discharge exceeding 10 mL/kg...
August 18, 2017: Digestive Surgery
https://www.readbyqxmd.com/read/28817370/conko-005-adjuvant-chemotherapy-with-gemcitabine-plus-erlotinib-versus-gemcitabine-alone-in-patients-after-r0-resection-of-pancreatic-cancer-a-multicenter-randomized-phase-iii-trial
#2
Marianne Sinn, Marcus Bahra, Torsten Liersch, Klaus Gellert, Helmut Messmann, Wolf Bechstein, Dirk Waldschmidt, Lutz Jacobasch, Martin Wilhelm, Bettina M Rau, Robert Grützmann, Arndt Weinmann, Georg Maschmeyer, Uwe Pelzer, Jens M Stieler, Jana K Striefler, Michael Ghadimi, Sven Bischoff, Bernd Dörken, Helmut Oettle, Hanno Riess
Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817187/second-line-treatment-in-patients-with-pancreatic-ductal-adenocarcinoma-a-meta-analysis
#3
Mohamad Bassam Sonbol, Belal Firwana, Zhen Wang, Diana Almader-Douglas, Mitesh J Borad, Issam Makhoul, Ramesh K Ramanathan, Daniel H Ahn, Tanios Bekaii-Saab
BACKGROUND: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC. METHODS: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28816351/recent-advances-in-genomic-profiling-of-adenosquamous-carcinoma-of-the-pancreas
#4
Rebecca Marcus, Anirban Maitra, Jason Roszik
Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole genome and exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP...
August 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28816013/new-neurotensin-analogue-radiolabeled-by-99m-technetium-as-a-potential-agent-for-tumor-identification
#5
Iman Emrarian, Nourollah Sadeghzadeh, Seyed Mohammad Abedi, Saeid Abediankenari
INTRODUCTION: It has been shown that more than 75% of ductal pancreatic adenocarcinomas are overexpress neurotensin (NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non-invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor-positive tumors such as pancreatic carcinoma. METHODS: Radiolabeling was performed at 95°C for 10 min using(99m) Tc in the presence of tricine/EDDA exchange labeling...
August 16, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28815403/overexpression-of-topoisomerase-2-alpha-confers-a-poor-prognosis-in-pancreatic-adenocarcinoma-identified-by-co-expression-analysis
#6
Zhou Zhou, Shi Liu, Meng Zhang, Rui Zhou, Jing Liu, Ying Chang, Qiu Zhao
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of human cancer-related death in the developed countries. Its progression and prognosis are influenced by a complex network of gene interactions. AIMS: The purpose of this study is to explore key genes associated with pancreatic ductal adenocarcinoma and to predict the possible mechanisms. METHODS: A weighted gene co-expression network was constructed to identify gene modules associated with the progression of PDAC...
August 16, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28813661/tissue-resident-macrophages-in-pancreatic-ductal-adenocarcinoma-originate-from-embryonic-hematopoiesis-and-promote-tumor-progression
#7
Yu Zhu, John M Herndon, Dorothy K Sojka, Ki-Wook Kim, Brett L Knolhoff, Chong Zuo, Darren R Cullinan, Jingqin Luo, Audrey R Bearden, Kory J Lavine, Wayne M Yokoyama, William G Hawkins, Ryan C Fields, Gwendalyn J Randolph, David G DeNardo
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813653/the-yolk-sac-feeds-pancreatic-tumors
#8
Jeffrey W Pollard
In this issue of Immunity, Zhu et al. (2017) report that tumor-associated macrophages in a mouse model of pancreatic ductal adenocarcinoma (PDAC) originate from both the yolk sac (YS) and bone marrow. Differential ablation of these populations indicates that only the YS-derived macrophages promote PDAC progression and growth.
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#9
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/28811674/regenerative-medicine-and-cell-based-approaches-to-restore-pancreatic-function
#10
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/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#11
(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
#12
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
#13
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
#14
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
#15
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
#16
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/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#17
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)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803603/prognostic-impact-of-cell-division-cycle-associated-2-expression-on-pancreatic-ductal-adenocarcinoma
#18
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/28802189/pt-but-not-pn-stage-of-the-8th-tnm-classification-significantly-improves-prognostication-in-pancreatic-ductal-adenocarcinoma
#19
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
#20
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
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