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https://www.readbyqxmd.com/read/28819564/a-review-of-the-impact-of-obesity-on-common-gastrointestinal-malignancies
#1
Somashekar G Krishna, Hisham Hussan, Zobeida Cruz-Monserrate, Lanla F Conteh, Khalid Mumtaz, Darwin L Conwell
Obesity is a global pandemic and is a well-recognized risk factor for various gastrointestinal diseases. The prevalence of obesity is increasing across all age groups. There is an emergent need for focused guidelines aimed at reducing the incidence, prevalence, and associated risks of obesity. The impact of obesity on gastrointestinal cancers being multifactorial adversely influences the associated risk, disease course, prognosis, and overall survival. We have summarized the current literature highlighting the association between obesity and common gastrointestinal cancers, with specific focus on esophageal adenocarcinoma, colon cancer, hepatocellular cancer, cholangiocarcinoma, and pancreatic malignancies...
2017: Integrative Cancer Science and Therapeutics
https://www.readbyqxmd.com/read/28817822/predictors-of-postoperative-non-chylous-massive-discharge-after-pancreaticoduodenectomy-for-pancreatic-ductal-adenocarcinoma
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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/28813624/tp53-mutational-status-and-ros-effect-the-expression-of-the-survivin-associated-radio-adaptive-response
#10
Jeffrey S Murley, Richard C Miller, Ralph R Weichselbaum, David J Grdina
A survivin-associated radio-adaptive response, characterized by increased radiation resistance or sensitization, was induced by exposure to 5 mGy of ionizing radiation and was correlated to the TP53 mutational status of exposed cells. Ten human cancer lines were investigated: colorectal carcinomas HCT116 and RKO [TP53 wild-type (WT)] and their respective TP53 null isogenic lines; breast adenocarcinomas MCF7 (TP53 WT) and MDA-MB-231 (TP53 Mut); lung carcinomas A549 (TP53 WT) and NCI-H1975 (TP53 Mut); and pancreatic carcinomas Hs766T (TP53 WT) and Panc-1 (TP53 Mut)...
August 16, 2017: Radiation Research
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#11
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
#12
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
#13
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
#14
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
#15
(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
#16
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
#17
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
#18
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
#19
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
#20
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
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