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https://www.readbyqxmd.com/read/27902695/text-mining-genotype-phenotype-relationships-from-biomedical-literature-for-database-curation-and-precision-medicine
#1
Ayush Singhal, Michael Simmons, Zhiyong Lu
The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27888869/latest-advances-in-chronic-pancreatitis
#2
J Enrique Domínguez-Muñoz
This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the definition of the disease, the etiological diagnosis of idiopathic disease, the correlation between fibrosis degree and pancreatic secretion in the early stages of chronic pancreatitis, the treatment of the disease and of pain, the clinical relevance of pancreatic exocrine insufficiency, and the diagnosis of autoimmune pancreatitis. A new mechanistic definition of chronic pancreatitis has been proposed...
September 2016: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/27855278/cadherin-11-is-a-cell-surface-marker-up-regulated-in-activated-pancreatic-stellate-cells-and-is-involved-in-pancreatic-cancer-cell-migration
#3
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael Weisman, Erika Noss, Michael Brenner, Brent Larson, Maha Guindi, Qiang Wang, Stephen J Pandol
Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined...
November 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27821712/btk-small-molecule-inhibitors-induce-a-distinct-pancreatic-toxicity-in-rats
#4
Rebecca I Erickson, Leah K Schutt, Jacqueline Tarrant, Michelle McDowell, Lichuan Liu, Adam R Johnson, Sock-Cheng Lewin-Koh, Maj Hedehus, Jed Ross, Richard A D Carano, Karin Staflin, Fiona Zhong, James Crawford, Shelly Zhong, Karin Reif, Arna Katewa, Harvey Wong, Wendy Young, Donna Dambach, Dinah Misner
Bruton's tyrosine kinase (BTK) is a member of the Tec family of cytoplasmic tyrosine kinases involved in B-cell and myeloid cell signaling. Small molecule inhibitors of BTK are being investigated for treatment of several hematological cancers and autoimmune diseases. GDC-0853 is a selective and reversible oral small molecule BTK inhibitor in development for the treatment of rheumatoid arthritis and systemic lupus erythematosus. In Sprague-Dawley (SD) rats, administration of GDC-0853 and other structurally diverse BTK inhibitors for 7 days or longer caused pancreatic lesions consisting of multifocal islet-centered hemorrhage, inflammation, fibrosis, and pigment-laden macrophages with adjacent lobular exocrine acinar cell atrophy, degeneration, and inflammation...
November 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27800195/an-unusual-case-of-gastrointestinal-bleeding-from-isolated-gallbladder-varices-in-a-patient-with-pancreatic-cancer-complicated-by-portal-biliopathy
#5
Mahir Gachabayov, Kubach Kubachev, Elbrus Abdullaev, Nonna Zarkua, Abakar Abdullaev, Artur Fokin
Portal biliopathy is the complex of abnormalities of extrahepatic and intrahepatic bile ducts, cystic duct, and gallbladder, arising as a result of extrahepatic portal vein obstruction and noncirrhotic portal fibrosis, which can be caused by coagulopathies, tumors, inflammation, postoperative complications, dehydration, and neonatal umbilical vein catheterization. We report a case of a 55-year-old male patient with the history of pancreatic cancer and cholecystoenteric anastomosis presenting with gastrointestinal bleeding from gallbladder varices via the anastomosis...
2016: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/27798096/chronic-pancreatitis-and-lipomatosis-are-associated-with-defective-function-of-ciliary-genes-in-pancreatic-ductal-cells
#6
Cécile Augereau, Louis Collet, Pierfrancesco Vargiu, Carmen Guerra, Sagrario Ortega, Frédéric P Lemaigre, Patrick Jacquemin
Genetic diseases associated with defects in primary cilia are classified as ciliopathies. Pancreatic lesions and ductal cysts are found in patients with ciliopathic polycystic kidney diseases suggesting a close connection between pancreatic defects and primary cilia. Here we investigate the role of two genes whose deletion is known to cause primary cilium defects, namely Hnf6 and Lkb1, in pancreatic ductal homeostasis. We find that mice with postnatal duct-specific deletion of Hnf6 or Lkb1 show duct dilations...
October 7, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27780664/vascular-enhancement-pattern-of-mass-in-computed-tomography-may-predict-chemo-responsiveness-in-advanced-pancreatic-cancer
#7
Shin Il Kim, Jun Young Shin, Jin-Seok Park, Seok Jeong, Yong Sun Jeon, Moon Han Choi, Hyun Jong Choi, Jong Ho Moon, Jae Chul Hwang, Min Jae Yang, Byoung Moo Yoo, Jin Hong Kim, Hyun Woo Lee, Chang-Il Kwon, Don Haeng Lee
INTRODUCTION: Chemo-responsiveness in pancreatic cancer is known to be dependent on fibrosis and vascularity. The purpose of this study was to assess vascular enhancement in advanced pancreatic adenocarcinoma with or without liver metastasis in computed tomography (CT) and to analyze the correlation between enhancement patterns and chemo-responsiveness. METHODS: Patients were assigned to either a responder group (partial response or stable disease) or a non-responder group (progressive disease) according to chemo-responsiveness assessed by CT before and after gemcitabine-based chemotherapy...
October 19, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/27733144/successful-treatment-of-gemcitabine-induced-acute-interstitial-pneumonia-with-imatinib-mesylate-a-case-report
#8
Elisabetta Fenocchio, Ilaria Depetris, Delia Campanella, Lucia Garetto, Fabrizio Carnevale Schianca, Danilo Galizia, Giovanni Grignani, Massimo Aglietta, Francesco Leone
BACKGROUND: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM)...
October 12, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27681847/regression-grading-in-neoadjuvant-treated-pancreatic-cancer-an-interobserver-study
#9
Sangeetha N Kalimuthu, Stefano Serra, Neesha Dhani, Sara Hafezi-Bakhtiari, Eva Szentgyorgyi, Rajkumar Vajpeyi, Runjan Chetty
AIM: Several regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems. METHODS: Four gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7-20 slides from each case) of neoadjuvant chemoradiation-treated PDAC...
September 28, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27670661/role-of-trpc1-channels-in-pressure-mediated-activation-of-murine-pancreatic-stellate-cells
#10
Benedikt Fels, Nikolaj Nielsen, Albrecht Schwab
The tumor environment contributes importantly to tumor cell behavior and cancer progression. Aside from biochemical constituents, physical factors of the environment also influence the tumor. Growing evidence suggests that mechanics [e.g., tumor (stroma) elasticity, tissue pressure] are critical players of cancer progression. Underlying mechanobiological mechanisms involve among others the regulation of focal adhesion molecules, cytoskeletal modifications, and mechanosensitive (MS) ion channels of cancer- and tumor-associated cells...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27665173/clinical-significance-of-serum-wisteria-floribunda-agglutinin-positive-mac-2-binding-protein-in-pancreatic-ductal-adenocarcinoma
#11
Yuichi Waragai, Rei Suzuki, Tadayuki Takagi, Mitsuru Sugimoto, Hiroyuki Asama, Ko Watanabe, Hitomi Kikuchi, Takuto Hikichi, Atsushi Masamune, Ya'an Kang, Jason B Fleming, Hiromasa Ohira
BACKGROUND: Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA(+)-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA(+)-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. METHODS: In this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA(+)-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA(+)-M2BP, we investigated the presence of WFA(+)-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53)...
September 7, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/27641067/new-player-in-tumor-stromal-interaction-granulin-as-a-novel-therapeutic-target-for-pancreatic-ductal-adenocarcinoma-liver-metastasis
#12
Misako Sato-Matsubara, Norifumi Kawada
Nielsen SR, Quaranta V, Linford A, et al.(1) (Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol. 2016;18:549-60) recently described a new mechanism for the tumor-stromal interaction in the metastatic progression of pancreatic ductal adenocarcinoma (PDAC) in the liver via granulin that is secreted by metastasis-associated macrophages (MAMs).(1) MAM-derived granulin transactivates hepatic stellate cells (hStCs), which leads to the production of periostin and extracellular matrix (ECM) at the metastatic site...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27627810/generation-of-an-in%C3%A2-vitro-3d-pdac-stroma-rich-spheroid-model
#13
Matthew J Ware, Vazrik Keshishian, Justin J Law, Jason C Ho, Carlos A Favela, Paul Rees, Billie Smith, Sayeeduddin Mohammad, Rosa F Hwang, Kimal Rajapakshe, Cristian Coarfa, Shixia Huang, Dean P Edwards, Stuart J Corr, Biana Godin, Steven A Curley
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma...
November 2016: Biomaterials
https://www.readbyqxmd.com/read/27613407/a-potential-role-for-ccn2-ctgf-in-aggressive-colorectal-cancer
#14
Inge Ubink, Elisha R Verhaar, Onno Kranenburg, Roel Goldschmeding
CCN2, also known as connective tissue growth factor (CTGF) is a transcriptional target of TGF-β signaling. Unlike its original name ("CTGF") suggested, CCN2 is not an actual growth factor but a matricellular protein that plays an important role in fibrosis, inflammation and connective tissue remodeling in a variety of diseases, including cancer. In pancreatic ductal adenocarcinoma, CCN2 signaling induces stromal infiltration and facilitates a strong tumor-stromal interaction. In many types of cancer, CCN2 overexpression has been associated with poor outcome...
September 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27602112/localized-18-f-fluorodeoxyglucose-uptake-at-the-pancreatic-head-during-remission-phase-of-autoimmune-pancreatitis-a-case-report
#15
Yoshikuni Yonenaga, Fumiki Kushihata, Jota Watanabe, Taiji Tohyama, Hitoshi Inoue, Atsuro Sugita, Yasutsugu Takada
Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography...
September 2016: Oncology Letters
https://www.readbyqxmd.com/read/27542226/novel-regulatory-role-of-neuropilin-1-in-endothelial-to-mesenchymal-transition-and-fibrosis-in-pancreatic-ductal-adenocarcinoma
#16
Pratiek N Matkar, Krishna Kumar Singh, Dmitriy Rudenko, Yu Jin Kim, Michael A Kuliszewski, Gerald J Prud'homme, David W Hedley, Howard Leong-Poi
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an intense fibrotic reaction termed tumor desmoplasia, which is in part responsible for its aggressiveness. Endothelial cells have been shown to display cellular plasticity in the form of endothelial-to-mesenchymal transition (EndMT) that serves as an important source of fibroblasts in pathological disorders, including cancer. Angiogenic co-receptor, neuropilin-1 (NRP- 1) actively binds TGFβ1, the primary mediator of EndMT and is involved in oncogenic processes like epithelial-to-mesenchymal transition (EMT)...
August 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27496707/cancer-associated-fibroblasts-in-pancreatic-cancer-are-reprogrammed-by-tumor-induced-alterations-in-genomic-dna-methylation
#17
Qian Xiao, Donger Zhou, Agnieszka A Rucki, Jamila Williams, Jiaojiao Zhou, Guanglan Mo, Adrian Murphy, Kenji Fujiwara, Jennifer Kleponis, Bulent Salman, Christopher L Wolfgang, Robert A Anders, Shu Zheng, Elizabeth M Jaffee, Lei Zheng
Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer-associated fibroblasts (CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation at baseline. Silencing or decitabine treatment to block the DNA methylation enzyme DNMT1 inhibited methylation of SOCS1...
September 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27488376/nitric-oxide-signals-are-interlinked-with-calcium-signals-in-normal-pancreatic-stellate-cells-upon-oxidative-stress-and-inflammation
#18
Monika A Jakubowska, Pawel E Ferdek, Oleg V Gerasimenko, Julia V Gerasimenko, Ole H Petersen
The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs)...
August 2016: Open Biology
https://www.readbyqxmd.com/read/27487486/the-calpain-inhibitor-calpeptin-suppresses-pancreatic-cancer-by-disrupting-cancer-stromal-interactions-in-a-mouse-xenograft-model
#19
Masaki Yoshida, Yoshihiro Miyasaka, Kenoki Ohuchida, Takashi Okumura, Biao Zheng, Nobuhiro Torata, Hayato Fujita, Toshinaga Nabae, Tatsuya Manabe, Masaya Shimamoto, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura
Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several anti-fibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of desmoplasia-targeting anti-fibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model...
August 3, 2016: Cancer Science
https://www.readbyqxmd.com/read/27449741/comparison-of-picrosirius-red-staining-with-second-harmonic-generation-imaging-for-the-quantification-of-clinically-relevant-collagen-fiber-features-in-histopathology-samples
#20
Cole R Drifka, Agnes G Loeffler, Kara Mathewson, Guneet Mehta, Adib Keikhosravi, Yuming Liu, Stephanie Lemancik, William A Ricke, Sharon M Weber, W John Kao, Kevin W Eliceiri
Stromal collagen alignment has been shown to have clinical significance in a variety of cancers and in other diseases accompanied by fibrosis. While much of the biological and clinical importance of collagen changes has been demonstrated using second harmonic generation (SHG) imaging in experimental settings, implementation into routine clinical pathology practice is currently prohibitive. To translate the assessment of collagen organization into routine pathology workflow, a surrogate visualization method needs to be examined...
September 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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