Depletion of CD4+ T-helper cells reduces pancreatic damage in two models of acute pancreatitis.
Objectives Acute pancreatitis is characterized as self-digestion of the pancreas by its own proteases. This process is accompanied by a local and systemic immune response. While cells of the innate immune system migrate into the pancreas, cells of the adaptive immune system like T-cells do not infiltrate the organ, but still undergo activation in the spleen and the surrounding lymph-nodes. The aim of this study was to investigate the role of T-cells during acute pancreatitis. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Juliane Glaubitz, Anika Wilden, Cindy van den Brandt, Frank Ulrich Weiss, Julia Mayerle, Markus M. Lerch, Matthias Sendler Tags: 3. Experimental Pancreatitis I Source Type: research
LMP7 immunoproteasome knockout mice show delayed inflammatory response during acute pancreatitis: protective or harmful effect?
Objectives Acute pancreatitis is a primarily sterile disease characterized by a severe systemic inflammatory response associated with extensive necrosis and a mortality rate of up to 24%. Since some studies have linked the proteasome with immune response activation, mainly through LMP7 immunoproteasome subunit inhibition, our aim in this work was to investigate its role in pancreatitis. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Laura Let ícia de Freitas Chama, Frank Ulrich Weiß, Elke Krüger, Markus M. Lerch, Matthias Sendler Tags: 3. Experimental Pancreatitis I Source Type: research
Biliary micro-crystals cause NLRP3-mediated inflammasome activation
Objectives Presence of biliary micro-crystals in biliary sludge is strongly associated with idiopathic pancreatitis. Patients with biliary micro-crystals may be at higher risk for developing pancreatitis due to crystal-induced damage. We hypothesize that biliary micro-crystals could induce inflammasome activation and subsequent local inflammation. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Philipp Vetter, Ujjwal Mukund Mahajan, Ivonne Regel, Matthias Sendler, Georg Beyer, Julia Mayerle Tags: 3. Experimental Pancreatitis I Source Type: research
Expression of the obestatin/G-protein coupled receptor 39 (GPR39) system in healthy and diseased human pancreas
Objectives Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines. Our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. Although this system has been described in the rat endocrine pancreas, its exact expression and function in human pancreas has not been assessed yet. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Lara Est évez-Perez, Saul Leal-lopez, Agustin Sanchez-Temprano, Begoña Otero-Alen, Carlos Seoane-Mosteiro, Rosalia Gallego- Gomez, Ihab Abdulkader-Nallib, Tomas Garcia-Caballero, J Enrique Dominguez-Muñoz, Jesus Perez-Camiña, Yolanda Pazos-Randulfe Tags: 4. Genetics in pancreatic diseases Source Type: research
Subsequent malignant neoplasms among pancreatic cancer long-term survivors; new potential hereditary genetic alterations
Objectives Subsequent secondary malignant neoplasm (SMN) develop only a few pancreatic ductal adenocarcinoma (PDAC) survivors. Major aim of this study was to describe development of secondary malignancies among long-term PDAC survivors and to analyze their germline genetic background. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Martin Lovecek, Marketa Janatova, Pavel Skalicky, Tomas Zemanek, Ondrej Strouhal, Petra Zemankova, Klara Lhotova, Marianna Borecka, Jana Soukupova, Hana Svebisova, Pavel Soucek, Viktor Hlavac, Zdenek Kleibl, Beatrice Mohelnikova-Duchonova Tags: 4. Genetics in pancreatic diseases Source Type: research
CFTR mutations relevance on pancreatitis outcome: genotype-phenotype correlation and impact of associated factors
The objectives were: to describe the natural history of CFTR-associated pancreatitis; to assess a genotype-phenotype correlation; to specify the role of environmental risk factors; and to assess the risk of pancreatic cancer. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Sol ène Dermine, Emmanuelle Girodon-Boulandet, Paul Calame, Marie Pierre Vullierme, Thierry Bienvenu, Philippe Ruszniewski, Philippe Levy, Vinciane Rebours Tags: 4. Genetics in pancreatic diseases Source Type: research
Association between CEL-HYB1 allele and idiopathic/familial chronic pancreatitis in Polish pediatric patients
Objectives Introduction: Recombination between the carboxyl ester lipase gene (CEL) and its pseudogene (CELP) can create the CEL-HYB1 allele, which encodes a fusion protein consisting of the proximal part of CEL and the distal part of CELP. CEL-HYB1 has recently been shown to elevate susceptibility to chronic pancreatitis (CP) in European patients. In Asian populations, a similar allele (designated CEL-HYB2) is present, however, is not associated with CP risk. These observations suggest that CEL-HYB1 is CP risk factor primarily in European populations, but replication studies are lacking. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Aleksandra Anna Kujko, Grzegorz Oracz, Karianne Fjeld, Karolina Wejnarska, Katarzyna Wertheim-Tysarowska, Elwira Ko łodziejczyk, Jerzy Bal, Wioletta Adamus-Białek, Dorota Kozieł, Artur Kowalik, Stanisław Głuszek, Anders Molven, Agnieszka Magdalena Ry Tags: 4. Genetics in pancreatic diseases Source Type: research
Differences in CTRB1 and CTRB2 promotor activities imply new pathomechanism of associated pancreatitis risk
This study investigates the promotor activity of CTRB1 and CTRB2 to further elucidating the mechanism. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Sebastian Beer, Alexandra Demcs ák, Katharina Seltsam, Joachim Mössner, Jonas Rosendahl Tags: 4. Genetics in pancreatic diseases Source Type: research
Follow-up as analysis tool of the potential long-term effects of SPINK, CTRC mutations in Acute Pancreatitis Patients
Objectives In recent years genetic mutations are perceived as one of the risk factor in acute pancreatitis (AC) as well as pancreatic cancer (PC). It seems that known genetic mutations SPINK, CTRC are also crucial for the risk of recurrences of AC. The aim of this study was to evaluate the frequency of the recurrences in group with and without selected mutations. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Dorota Kozie ł, Jaroslaw Matykiewicz, Monika Wawszczak, Michał Majchrzak, Wioletta Adamus-Bialek, Stanislaw Gluszek Tags: 4. Genetics in pancreatic diseases Source Type: research
Impact of known SPINK1 missense variants on pre-mRNA splicing and/or mRNA stability in a full-length gene assay
Objectives Any variants occurring within coding sequences of genes may affect pre-mRNA splicing and/or mRNA stability; and up to 10% of known disease-associated missense variants were reported to alter pre-mRNA splicing. SPINK1 is one of the most studied chronic pancreatitis-predisposing genes, and a large number of variants including missense ones have been reported. Here we describe the effects of all previously reported SPINK1 missense variants (n=24) on pre-mRNA splicing and/or mRNA stability that were evaluated in a full-length gene assay. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Arnaud Boulling, Hao Wu, Wen-Bin Zou, Emmanuelle Masson, Claude F érec, Jian-Min Chen Tags: 4. Genetics in pancreatic diseases Source Type: research
NGS sequencing as an efficient instrument of molecular genetic diagnostics in patients with chronic pancreatitis
In this study, the contribution of genetic factors to the development of chronic pancreatitis has been analyzed. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Kamil F. Khafizov, Mariya M. Litvinova, Andrei A. Ayginin, Alina D. Matsvay, Ekaterina V. Pimkina, Anna S. Speranskaya, German A. Shipulin, Ludmila V. Vinokurova, Karine A. Nikolskaya, Elena A. Dubtsova, Dmitry S. Bordin Tags: 4. Genetics in pancreatic diseases Source Type: research
The polymorphic carboxyl-ester lipase (CEL) gene: novel copy number variants (CNVs) identified by both classical and high-throughput genetic analysis
Objectives We have previously identified CNVs of CEL: one duplication allele (CEL-DUP1) and a recombined deletion allele (CEL-HYB), the latter being a risk factor for chronic pancreatitis. We found no association between these CEL alleles and pancreatic cancer (Dalva et al., Pancreatology 2017). However, we identified subjects with CEL sequence gain, who tested negative for CEL-DUP1. Here we aimed to characterize these new CEL variants and to investigate their association with pancreatic disease. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Karianne Fjeld, Emmanuelle Masson Masson, Patrick Michl, Tomasz Stokowy, He Lin, Solrun J. Steine, Bente B. Johansson, Monica Dalva, Khadija El Jellas, Claudia Ruffert, Wen-Bin Zou, Zhao-Shen Li, P ål R Njølstad, Jian-Min Chen, Zhuan Liao, Stefan Johans Tags: 4. Genetics in pancreatic diseases Source Type: research
Different effects of frameshift mutations occurring in the repeat region of the pancreatic enzyme carboxyl ester lipase (CEL)
Objectives We have previously identified disease-associated mutations in the last exon of the CEL gene, localized in a variable number of tandem repeats (VNTR) region. Two single-base deletions (DEL1, DEL4) lead to frameshifts that predict a new, long C-terminus of the CEL protein, and deletion carriers suffer from exocrine pancreatic dysfunction and diabetes. Moreover, single-base insertions (denoted INS) are common in the CEL VNTR and result in frameshifts that truncate the protein after only five new amino acids. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Anny Gravdal, Ranveig Seim Brekke, Khadija El Jellas, Xunjun Xiao, Mark E. Lowe, Dominique Lombardo, Eric Mas, Bente Berg Johansson, Karianne Fjeld, Anders Molven Tags: 4. Genetics in pancreatic diseases Source Type: research
The PANcreatic DISEASE ReseArch (PANDoRA) consortium: an update
Objectives In recent years progress has been made to elucidate the genetic component of pancreatic cancer risk, but much remains to be done. Multicentric studies have been of the uttermost importance to identify genetic factors involved in neoplastic diseases. We have established the PANcreatic Disease ReseArch (PANDoRA) consortium to strengthen efforts of different research groups and have created a large bio- and databank aimed at uncovering new genetic factors for pancreatic cancer risk and survival. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Federico Canzian, Ofure Obazee, Thilo Hackert, John P. Neoptolemos, Oliver Strobel, Yogesh K. Vashist, Jakob R. Izbicki, Rudolf Kaaks, Hermann Brenner, Peter Hegyi, Ugo Boggi, Luca Morelli, Franco Bambi, Gabriele Capurso, Raffaele Pezzilli, Andrea Mambrin Tags: 4. Genetics in pancreatic diseases Source Type: research
The mutations of carboxypeptidase 1 predisposes to distinguishing patients with acute pancreatitis and pancreatic cancer
Objectives Environmental factors in connection with genetic factors play an important role in the development of pancreatitis and pancreatic cancer. The aim of the study was the DNA sequences analysis of CPA1 gene to identification of specific sites correlating with pancreatic cancer (PC) and acute pancreatitis (AP). (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Stanislaw Gluszek, Monika Wawszczak, Micha ł Majchrzak, Wioletta Adamus-Bialek, Justyna Klusek, Lukasz Nawacki, Dorota Kozieł Tags: 4. Genetics in pancreatic diseases Source Type: research
