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Pancreatic acinar cells

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https://www.readbyqxmd.com/read/28103943/a-primary-pure-pancreatic-type-acinar-cell-carcinoma-of-the-stomach-a-case-report
#1
Kyoung Min Kim, Chan Young Kim, Seung-Mo Hong, Kyu Yun Jang
BACKGROUND: Acinar cell carcinoma represents only 1-2% of exocrine pancreatic neoplasms. On exceptionally rare occasions, primary acinar cell carcinoma can occur in ectopic locations. Herein, we report a case of pure pancreatic-type acinar cell carcinoma arising in the stomach. CASE PRESENTATION: A 54-year-old male presented with a gastric submucosal mass detected by endoscopic examination. Laparoscopic wedge resection was performed. Macroscopically, the 2.7 cm yellowish mass was located in the submucosa of the stomach...
January 19, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28099259/smad2-3-linker-phosphorylation-is-a-possible-marker-of-pancreatic-stem-progenitor-cells-in-the-regenerative-phase-of-acute-pancreatitis
#2
Masayuki Sakao, Yutaku Sakaguchi, Ryo Suzuki, Yu Takahashi, Masanobu Kishimoto, Toshiro Fukui, Kazushige Uchida, Akiyoshi Nishio, Koichi Matsuzaki, Kazuichi Okazaki
OBJECTIVES: The aims of this study are to characterize cell proliferation and differentiation during regeneration after pancreatitis and pancreatic buds during development to evaluate the role of Smad2/3, phosphorylated at the specific linker threonine residues (pSmad2/3L-Thr) in positive cells. METHODS: Male C57BL/6 mice received hourly intraperitoneal injections of cerulein and were analyzed after induced pancreatitis. Pancreatitis-affected tissue sections and pancreatic buds were immunostained for pSmad2/3L-Thr, with other markers thought to be stem/progenitor markers of the pancreas...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-egf-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#3
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a 3-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#4
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28090570/targeted-inhibition-of-pancreatic-acinar-cell-calcineurin-is-a-novel-strategy-to-prevent-post-ercp-pancreatitis
#5
Abrahim I Orabi, Li Wen, Tanveer A Javed, Tianming Le, Ping Guo, Subramaniam Sanker, David Ricks, Kristy Boggs, John F Eisses, Carlos Castro, Xiangwei Xiao, Krishna Prasadan, Farzad Esni, George K Gittes, Sohail Z Husain
BACKGROUND AND AIMS: There is a pressing need to develop effective preventative therapies for post-ERCP pancreatitis (PEP). We demonstrated that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. METHODS: We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel AAV-Ela-iCre into the pancreatic duct of a calcineurin floxed line...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#6
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
December 27, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#7
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28087712/pdx1-dynamically-regulates-pancreatic-ductal-adenocarcinoma-initiation-and-maintenance
#8
Nilotpal Roy, Kenneth K Takeuchi, Jeanine M Ruggeri, Peter Bailey, David Chang, Joey Li, Laura Leonhardt, Sapna Puri, Megan T Hoffman, Shan Gao, Christopher J Halbrook, Yan Song, Mats Ljungman, Shivani Malik, Christopher V E Wright, David W Dawson, Andrew V Biankin, Matthias Hebrok, Howard C Crawford
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28057438/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#9
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28042334/visualization-quantification-and-characterization-of-caerulein-induced-acute-pancreatitis-in-rats-by-3-0t-clinical-mri-biochemistry-and-histomorphology
#10
Ting Yin, Ronald Peeters, Yewei Liu, Yuanbo Feng, Xinyuan Zhang, Yansheng Jiang, Jie Yu, Steven Dymarkowski, Uwe Himmelreich, Raymond Oyen, Yicheng Ni
Purpose: To investigate whether Caerulein-induced acute pancreatitis (AP) in rats could be noninvasively studied by clinical magnetic resonance imaging (MRI) techniques and validated by enzymatic biochemistry and histomorphology. Materials and Methods: The study was approved by the institutional animal ethical committee. The AP was induced in 26 rats by intraperitoneal injections of Caerulein, as compared to 6 normal rats. T2-weighted 3D MRI, T2 relaxation measurement and contrast enhanced T1-weighted MRI were performed at 3 Tesla...
2017: Theranostics
https://www.readbyqxmd.com/read/28009527/reg2-expression-is-required-for-pancreatic-islet-compensation-in-response-to-aging-and-high-fat-diet-induced-obesity
#11
Qing Li, Bing Li, Xiaoliang Miao, Christopher Ramgattie, Zu-Hua Gao, Jun-Li Liu
Maintaining pancreatic β-cell mass and function is essential for normal insulin production and glucose homeostasis. Regenerating islet-derived 2 (Reg2, Reg II, human orthologue Reg1B) gene is normally expressed in pancreatic acinar cells and significantly induced in responses to diabetes, pancreatitis, high-fat diet and during pancreatic regeneration. In order to evaluate the role of endogenous Reg2 production in normal β-cell function, we characterized Reg2 gene deficient mice normally and when subjected to several pathological challenges...
December 23, 2016: Endocrinology
https://www.readbyqxmd.com/read/27992669/midkine-is-overexpressed-in-acute-pancreatitis-and-promotes-the-pancreatic-recovery-in-l-arginine-induced-acute-pancreatitis-in-mice
#12
Li Cheng, Zhenguo Qiao, Chunfang Xu, Jiaqing Shen
BACKGROUND AND AIM: Midkine (MK) is involved in the pathogenesis of numerous malignancies, but the expression and effect of MK in acute pancreatitis (AP) have not been well studied and documented. METHODS: In this study, the expression of MK was assayed in mice with L-arginine-induced AP. A recombinant protein of MK (rhMK) was introduced in this study to test the effect of MK on the L-arginine-induced AP. Serum amylase and lipase were assayed. Pancreas tissue samples were also collected for the evaluation of histologic injury...
December 19, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27991926/chronic-inflammation-initiates-multiple-forms-of-k-ras-independent-mouse-pancreatic-cancer-in-the-absence-of-tp53
#13
A K Swidnicka-Siergiejko, S B Gomez-Chou, Z Cruz-Monserrate, D Deng, Y Liu, H Huang, B Ji, N Azizian, J Daniluk, W Lu, H Wang, A Maitra, C D Logsdon
Chronic inflammation (CI) is a risk factor for pancreatic cancer (PC) including the most common type, ductal adenocarcinoma (PDAC), but its role and the mechanisms involved are unclear. To investigate the role of CI in PC, we generated genetic mouse models with pancreatic specific CI in the presence or absence of TP53. Mice were engineered to express either cyclooxygenase-2 (COX-2) or IκB kinase-2 (IKK2), and TP53(+/+) or TP53(f/f) specifically in adult pancreatic acinar cells by using a full-length pancreatic elastase promoter-driven Cre...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27989643/serpini2-pancpin-is-an-inhibitory-serpin-targeting-pancreatic-elastase-and-chymotrypsin
#14
Wayne J Higgins, Gareth T Grehan, Kieran J Wynne, D Margaret Worrall
SerpinI2/Pancpin/MEPI is a 46kDa member of the serpin (serine protease inhibitor) superfamily. It is downregulated in pancreatic and breast cancer, and associated with acinar cell apoptosis and pancreatic insufficiency when absent in mice. However, the target protease and protein properties of serpinI2 are previously uncharacterised. We have expressed and purified recombinant serpin I2 in E. coli. The protein exhibited thermal instability typical of inhibitory serpins, which was lost following RCL cleavage...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27975299/nilotinib-a-tyrosine-kinase-inhibitor-exhibits-protection-against-acute-pancreatitis-induced-lung-and-liver-damage-in-rats
#15
Manar A Nader, Heba M Wagih
This investigation explored the nilotinib action in the management of acute pancreatitis (AP) and AP-induced lung and liver injury. AP was induced in Sprague Dawley (SD) rats with L-arginine. Treatment with nilotinib with or without L-arginine was applied for 7 days. Marked deterioration in serum amylase, lipase, aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), nitric oxide (NO), total protein content, and transforming growth factor beta1 (TGF-β1) along with pancreatic, hepatic, and pulmonary tissue lipid peroxidation (MDA) after induction of AP while significant reduction in tissues superoxide dismutase (SOD), glutathione (GSH) with marked edema, hemorrhage, and perivascular inflammation with acinar cell necrosis, along with elevated pancreatic percentage expression of TGF-β1 and nuclear factor kappa B (NF-κB), were observed in the AP group...
December 14, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27974199/glucagon-like-peptide-1-receptor-signaling-in-acinar-cells-causes-growth-dependent-release-of-pancreatic-enzymes
#16
Nicolai J Wewer Albrechtsen, Reidar Albrechtsen, Lasse Bremholm, Berit Svendsen, Rune E Kuhre, Steen S Poulsen, Charlotte B Christiansen, Elisa P Jensen, Charlotte Janus, Linda Hilsted, Carolyn F Deacon, Bolette Hartmann, Jens J Holst
Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27973548/the-chromatin-modifier-msk1-2-suppresses-endocrine-cell-fates-during-mouse-pancreatic-development
#17
Neha Bhat, Jeehye Park, Huda Y Zoghbi, J Simon C Arthur, Kenneth S Zaret
Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12...
2016: PloS One
https://www.readbyqxmd.com/read/27959400/resistin-aggravates-the-expression-of-proinflammatory-cytokines-in-cerulein%C3%A2-stimulated-ar42j-pancreatic-acinar-cells
#18
Chong-Yi Jiang, Wei Wang
Resistin, an adipocytokine secreted by fat tissues, has been shown to be associated with increased local and systemic complications in acute pancreatitis (AP). However, the mechanism underlying the effect of resistin in the aggravation of AP remains to be elucidated. The aim of the present study was to investigate the functional consequences of exposing rat pancreatic acinar cells to resistin and to determine whether it amplifies proinflammatory signaling in an in vitro AP model. AR42J cells pretreated with recombinant resistin were activated by cerulein as an in vitro model of AP...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27935983/involvement-of-pancreatic-stellate-cells-in-regeneration-of-remnant-pancreas-after-partial-pancreatectomy
#19
Shigenori Ota, Miyuki Nishimura, Yuya Murakami, Naoko Kubo Birukawa, Akihiro Yoneda, Hiroki Nishita, Ryosuke Fujita, Yasushi Sato, Kenjiro Minomi, Keiko Kajiwara, Miyono Miyazaki, Maki Uchiumi, Shintaro Mikuni, Yasuaki Tamura, Toru Mizuguchi, Masafumi Imamura, Makoto Meguro, Yasutoshi Kimura, Koichi Hirata, Yoshiro Niitsu
BACKGROUND AND OBJECTIVES: Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. METHODS: Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation...
2016: PloS One
https://www.readbyqxmd.com/read/27926361/nonductal-pancreatic-cancers
#20
REVIEW
Sun-Young Jun, Seung-Mo Hong
Nonductal pancreatic neoplasms, including solid pseudopapillary neoplasms, acinar cell carcinomas, and pancreatoblastomas, are uncommon. These entities share overlapping gross, microscopic, and immunohistochemical features, such as well-demarcated solid neoplasms, monotonous cellular tumor cells with little intervening stroma, and abnormal beta-catenin expression. Each tumor also has unique clinicopathologic characteristics with diverse clinical behavior. To differentiate nonductal pancreatic neoplasms, identification of histologic findings, such as pseudopapillae, acinar cell features, and squamoid corpuscles, is important...
December 2016: Surgical Pathology Clinics
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