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https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#1
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#2
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#3
Krishan Kumar, Brian T DeCant, Paul J Grippo, Rosa F Hwang, David J Bentrem, Kazumi Ebine, Hidayatullah G Munshi
The fibrotic reaction, which can account for over 70%-80% of the tumor mass, is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of collagen I production and fibrosis in vivo. In this report, we show that members of the bromodomain and extraterminal (BET) family of proteins are expressed in primary PSCs isolated from human PDAC tumors, with BRD4 positively regulating, and BRD2 and BRD3 negatively regulating, collagen I expression in primary cancer-associated PSCs...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28133225/-a-case-of-curative-resection-for-advanced-pancreatic-acinar-cell-carcinoma-with-liver-metastasis-and-involvement-of-the-superior-mesenteric-artery-after-chemoradiotherapy-following-systemic-chemotherapy
#4
Hiroko Toda, Hiroshi Kurahara, Kosei Maemura, Yuko Mataki, Yota Kawasaki, Masahiko Sakoda, Satoshi Iino, Shinichi Ueno, Hiroyuki Shinchi, Kanro Makisumi, Shoji Natsugoe
A 52-year-old man was initially diagnosed with an unresectable acinar cell carcinoma of the pancreas with liver metastasis and involvement of the superior mesenteric artery. After 5 courses of systemic chemotherapy(gemcitabine and S-1), the size of the pancreatic tumor had decreased from 31mm to 19mm and the liver metastasis had disappeared. We initiated chemoradiotherapy( CRT: S-1+56 Gy)for further local treatment. After CRT the size of the pancreatic tumor decreased to 13mm and his serum CA 19-9 level decreased from 677...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28126348/autophagy-is-required-for-activation-of-pancreatic-stellate-cells-associated-with-pancreatic-cancer-progression-and-promotes-growth-of-pancreatic-tumors-in-mice
#5
Sho Endo, Kohei Nakata, Kenoki Ohuchida, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Kazuhiro Koikawa, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Yusuke Mizuuchi, Chika Iwamoto, Masaharu Murata, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphological and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28109008/inhibition-of-group-1-p21-activated-kinases-suppresses-pancreatic-stellate-cell-activation-and-increases-survival-of-mice-with-pancreatic-cancer
#6
Dannel Yeo, Phoebe Phillips, Graham S Baldwin, Hong He, Mehrdad Nikfarjam
Pancreatic cancer remains one of the most lethal of all solid tumours. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21-activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using a modified outgrowth method. The effect of inhibiting PAK1 with a group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively...
January 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28105582/-control-of-opisthorchis-viverrini-infection-for-cholangiocarcinoma-prevention
#7
Y Buisson
The International Agency for Research on Cancer (IARC) has classified two liver flukes as carcinogenic to humans (Group 1): Opisthorchis viverrini in 1994 and Clonorchis sinensis in 2009. This review is focused on O. viverrini, the most studied of these two trematodes, which infects nearly 10 million people in Southeast Asia. The life cycle involves two intermediate hosts living in fresh water: a snail of the genus Bithynia and a ciprinid fish. The definitive hosts (human, cat, dog) become infected by ingesting raw fish containing metacercariae, the infective stage of the parasite...
January 19, 2017: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#8
Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28091744/prediction-of-pancreatic-fistula-after-distal-pancreatectomy-based-on-cross-sectional-images
#9
Ye Rim Chang, Jae Seung Kang, Jin-Young Jang, Woo Hyun Jung, Mee Joo Kang, Kyung Bun Lee, Sun-Whe Kim
BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common and clinically relevant complications after distal pancreatectomy (DP), occurring in 5-40% of patients. Determining risk factors for this complication may aid in its prevention. This study sought to predict the development of POPF after DP preoperatively and objectively based on radiologic findings. METHODS: This study included 60 patients who underwent DP using a stapler for pancreatic division between June 2011 and January 2013...
January 13, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#10
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28058076/non-alcoholic-fatty-pancreatic-disease-a-review-of-literature
#11
REVIEW
Hassan Tariq, Suresh Nayudu, Sai Akella, Mariela Glandt, Sridhar Chilimuri
There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome...
December 2016: Gastroenterology Research
https://www.readbyqxmd.com/read/28049396/oxidative-stress-and-antioxidant-potential-of-one-hundred-medicinal-plants
#12
Waseem Hassan, Hamsa Noreen, Shakila Rehman, Shehnaz Gul, Mohammad Amjad Kamal, Jean Paul Kamdem, Bakht Zaman, Joao B T da Rocha
Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc...
January 2, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27999205/muty-homolog-myh-inhibition-reduces-pancreatic-cancer-cell-growth-and-increases-chemosensitivity
#13
George Sharbeen, Janet Youkhana, Amanda Mawson, Joshua McCarroll, Andrea Nunez, Andrew Biankin, Amber Johns, David Goldstein, Phoebe Phillips
Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27902695/text-mining-genotype-phenotype-relationships-from-biomedical-literature-for-database-curation-and-precision-medicine
#14
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
#15
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
#16
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael H Weisman, Erika Noss, Michael B 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...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27821712/bruton-s-tyrosine-kinase-small-molecule-inhibitors-induce-a-distinct-pancreatic-toxicity-in-rats
#17
Rebecca I Erickson, Leah K Schutt, Jacqueline M 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 J Crawford, Shelly Zhong, Karin Reif, Arna Katewa, Harvey Wong, Wendy B Young, Donna M Dambach, Dinah L 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 hematologic cancers and autoimmune diseases. GDC-0853 ((S)-2-(3'-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4'-bipyridin]-2'-yl)-7,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one) is a selective and reversible oral small-molecule BTK inhibitor in development for the treatment of rheumatoid arthritis and systemic lupus erythematosus...
January 2017: 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
#18
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
#19
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
#20
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.]
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