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Pancreatic enzyme inhibitor

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https://www.readbyqxmd.com/read/28414320/inhibition-of-dna2-nuclease-as-a-therapeutic-strategy-targeting-replication-stress-in-cancer-cells
#1
S Kumar, X Peng, J Daley, L Yang, J Shen, N Nguyen, G Bae, H Niu, Y Peng, H-J Hsieh, L Wang, C Rao, C C Stephan, P Sung, G Ira, G Peng
Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity...
April 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28396512/pro-inflammatory-cytokine-driven-pi3k-akt-sp1-signaling-and-h2s-production-facilitates-the-pathogenesis-of-severe-acute-pancreatitis
#2
Ying Liu, Ribin Liao, Zhanrong Qiang, Cheng Zhang
Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulfide (H2S) that impairs the gastrointestinal (GI) system. However, the exact mechanism of H2S in the regulation of SAP is yet to be elucidated. In this paper, we use a rat model of SAP to evaluate the role of H2S on intestinal motility by counting the number of bowel movements and investigating the effect of H2S on inflammation...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28376184/a-plasma-biomarker-panel-to-identify-surgically-resectable-early-stage-pancreatic-cancer
#3
Seetharaman Balasenthil, Ying Huang, Suyu Liu, Tracey Marsh, Jinyun Chen, Sanford A Stass, Debra KuKuruga, Randall Brand, Nanyue Chen, Marsha L Frazier, J Jack Lee, Sudhir Srivastava, Subrata Sen, Ann McNeill Killary
Background: Blood-based biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Current biomarkers lack high sensitivity and specificity for population screening. The gold-standard biomarker, CA 19-9, also fails to demonstrate the predictive value necessary for early detection. Methods: To validate a functional genomics-based plasma migration signature biomarker panel, plasma tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FN III-C), and CA 19-9 levels were measured by enzyme-linked immunosorbent assays in three early-stage PDAC plasma cohorts, including two independent blinded validation cohorts containing a total of 43 stage I, 163 stage II, 86 chronic pancreatitis, 31 acute biliary obstruction, and 108 controls...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28335094/growth-and-physiological-responses-of-broiler-chickens-to-diets-containing-raw-full-fat-soybean-meal-and-supplemented-with-a-high-impact-microbial-protease
#4
Mammo Mengesha Erdaw, Shubiao Wu, Paul A Iji, Rider A Perez-Maldonado
Objective: This study was to evaluate the change and function of the pancreas, and small intestine in relation to growth performance of broilers on diets supplemented with raw soybean meal (RSBM) and protease. Samples of test ingredients and diets, after mixing and prior to being used were also assessed on contents of anti-nutritional factors. Methods: A 3 x 3 factorial study was used, with three levels of RSBM (commercial SBM was replaced by RSBM at 0, 10 or 20%) and protease (0...
March 21, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28334992/utility-of-chromogranin-b-compared-with-chromogranin-a-as-a-biomarker-in-japanese-patients-with-pancreatic-neuroendocrine-tumors
#5
Masami Miki, Tetsuhide Ito, Masayuki Hijioka, Lingaku Lee, Kohei Yasunaga, Keijiro Ueda, Takashi Fujiyama, Yuichi Tachibana, Ken Kawabe, Robert T Jensen, Yoshihiro Ogawa
Objective: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. Methods: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features...
March 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28323997/degradation-paradigm-of-the-gut-hormone-pancreatic-polypeptide-by-hepatic-and-renal-peptidases
#6
Joyceline Cuenco, James Minnion, Tricia Tan, Rebecca Scott, Natacha Germain, Yiin Ling, Rong Chen, Mohammad Ghatei, Stephen Bloom
Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial rise in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an antiobesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is degraded may aid design of long-acting PP analogues.We aimed to investigate the role of peptidases in PP degradation with a view to determining whether inhibition of these enzymes enhanced PP plasma levels and bioactivity in vivo...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#7
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28271914/monte-carlo-method-based-qsar-modelling-of-natural-lipase-inhibitors-using-hybrid-optimal-descriptors
#8
A Kumar, S Chauhan
Obesity is one of the most provoking health burdens in the developed countries. One of the strategies to prevent obesity is the inhibition of pancreatic lipase enzyme. The aim of this study was to build QSAR models for natural lipase inhibitors by using the Monte Carlo method. The molecular structures were represented by the simplified molecular input line entry system (SMILES) notation and molecular graphs. Three sets - training, calibration and test set of three splits - were examined and validated. Statistical quality of all the described models was very good...
March 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28270103/angiotensin-ii-receptor-blockers-and-risk-of-acute-pancreatitis-a-population-based-case-control-study-in-sweden
#9
Tomas S Bexelius, Rickard Ljung, Fredrik Mattsson, Yunxia Lu, Mats Lindblad
BACKGROUND: Acute pancreatitis is a potentially lethal disease, with a rising incidence in the Western world. Yet, no pharmacological prevention or specific treatment for acute pancreatitis exists. Also, the connection with severity of acute pancreatitis is unknown. Experimental and epidemiological research suggests a protective effect of angiotensin II receptor blockers. METHODS: During 2006 to 2008, we performed a nationwide case-control study on Swedish residents aged 40-84 years...
March 7, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28260082/cancer-associated-fibroblasts-enhance-pancreatic-cancer-cell-invasion-by-remodeling-the-metabolic-conversion-mechanism
#10
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Xijuan Cui, Hong Ji, Yiming Li, Ya'an Kang
We investigated the mechanism of cancer-associated fibroblasts (CAFs) in promoting the invasion and metastasis of pancreatic cancer cells in a non-vascular manner. We verified the original generation of isolated cultured CAFs and normal fibroblasts (NFs) based on the expression of α-SMA and vimentin, and we examined the cell glycolysis level through glucose consumption and lactate production experiments. The mRNA and protein expression of CAF glycolytic enzymes, lactate dehydrogenase and pyruvate kinase m2, were examined by RT-PCR and western blotting, respectively...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28247528/ace-inhibitors-and-the-risk-of-acute-pancreatitis-a-population-based-case-control-study
#11
Jaana Kuoppala, Hannes Enlund, Jukka Pulkkinen, Helena Kastarinen, Johanna Jyrkkä, Pertti Happonen, Hannu Paajanen
PURPOSE: The aim of this study was to examine the association between angiotensin converting enzyme (ACE) inhibitor use and the risk of acute pancreatitis. METHODS: Information on all 4966 cases hospitalized in 2008-2010 for acute pancreatitis was retrieved from the Finnish national registers on hospital discharges and prescriptions. A total of 24 788 age and sex-matched population-based controls were randomly selected using density sampling. ACE inhibitor use between 1 January 2003 and the index date were determined by the date of hospitalization for acute pancreatitis among the cases...
March 1, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28244615/geniposide-protects-pancreatic-%C3%AE-cells-from-high-glucose-mediated-injury-by-activation-of-amp-activated-protein-kinase
#12
Chunyan Liu, Yanan Hao, Fei Yin, Yonglan Zhang, Jianhui Liu
Our previous works indicated that geniposide could regulate glucose-stimulated insulin secretion (GSIS), and improved chronic high glucose-induced dysfunctions in pancreatic β cells, but the molecular mechanisms remain largely unknown. In the present study, we investigated the role of 5'-AMP-activated protein kinase (AMPK) in high glucose induced cell injury and explored the associated molecular mechanisms in rat INS-1 pancreatic β cells. Data suggested that geniposide obviously prevented the cell damage induced by high (25 mM) glucose in INS-1 cells, which increased the protein levels of cell apoptosis-associated enzymes, including heme oxygenase-1 (HO-1), and Bcl-2, but apparently attenuated the protein level of Bax, an apoptotic protein...
May 2017: Cell Biology International
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#13
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28186401/chemoproteomic-screening-of-covalent-ligands-reveals-uba5-as-a-novel-pancreatic-cancer-target
#14
Allison M Roberts, David K Miyamoto, Tucker R Huffman, Leslie A Bateman, Ashley N Ives, David Akopian, Martin J Heslin, Carlo M Contreras, Michael Rape, Christine F Skibola, Daniel K Nomura
Chemical genetic screening of small-molecule libraries has been a promising strategy for discovering unique and novel therapeutic compounds. However, identifying the targets of lead molecules that arise from these screens has remained a major bottleneck in understanding the mechanism of action of these compounds. Here, we have coupled the screening of a cysteine-reactive fragment-based covalent ligand library with an isotopic tandem orthogonal proteolysis-enabled activity-based protein profiling (isoTOP-ABPP) chemoproteomic platform to rapidly couple the discovery of lead small molecules that impair pancreatic cancer pathogenicity with the identification of druggable hotspots for potential cancer therapy...
February 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28170007/lactucaxanthin-a-potential-anti-diabetic-carotenoid-from-lettuce-lactuca-sativa-inhibits-%C3%AE-amylase-and-%C3%AE-glucosidase-activity-in-vitro-and-in-diabetic-rats
#15
Sowmya Shree Gopal, Magisetty Jhansi Lakshmi, Gurunathan Sharavana, Gunaseelan Sathaiah, Yadahally N Sreerama, Vallikannan Baskaran
Intestinal and pancreatic α-amylase and α-glucosidase inhibitors offer an approach to lower the levels of post-prandial hyperglycemia through the control of dietary starch breakdown in digestion. This study hypothesized that lactucaxanthin (Lxn) in lettuce (Lactuca sativa) inhibits the activity of α-amylase and α-glucosidase. In this study, the interaction of Lxn with α-amylase and α-glucosidase in silico and its inhibitory effect on these enzymes were studied using in vitro and STZ-induced diabetic rat models...
February 7, 2017: Food & Function
https://www.readbyqxmd.com/read/28167504/inhibition-of-isoprenylcysteine-carboxylmethyltransferase-induces-cell-cycle-arrest-and-apoptosis-through-p21-and-p21-regulated-bnip3-induction-in-pancreatic-cancer
#16
Kanjoormana Aryan Manu, Tin Fan Chai, Jing Tsong Teh, Wan Long Zhu, Patrick J Casey, Mei Wang
Pancreatic cancer remains one of the most difficult to treat human cancers despite recent advances in targeted therapy. Inhibition of Isoprenylcysteine carboxylmethyltransferase (ICMT), an enzyme that post-translationally modifies a group of proteins including several small GTPases, suppresses proliferation of some human cancer cells. However, the efficacy of ICMT inhibition on human pancreatic cancer has not been evaluated. In this study we have evaluated a panel of human pancreatic cancer cell lines and identified those that are sensitive to ICMT inhibition...
February 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28157665/inhibition-of-cancer-migration-and-invasion-by-knocking-down-delta-5-desaturase-in-cox-2-overexpressed-cancer-cells
#17
Xiaoyu Yang, Yi Xu, Tao Wang, Dan Shu, Peixuan Guo, Keith Miskimins, Steven Y Qian
We recently reported that knockdown of delta-5-desaturase (a key enzyme that converts dihomo-γ-linolenic acid, DGLA, to the downstream ω-6 arachidonic acid) promotes formation of an anti-cancer byproduct 8-hydroxyoctanoic acid from cyclooxygenase (COX)-catalyzed DGLA peroxidation. 8-hydroxyoctanoic acid can exert its growth inhibitory effect on cancer cells (e.g. colon and pancreatic cancer) by serving as a histone deacetylase inhibitor. Since histone deacetylase inhibitors have been well-known to suppress cancer cell migration and invasion, we thus tested whether knockdown of delta-5-desaturase and DGLA treatment could also be used to inhibit cancer migration and invasion of colon cancer and pancreatic cancer cells...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28124052/the-chemical-profiling-of-loquat-leaf-extract-by-hplc-dad-esi-ms-and-its-effects-on-hyperlipidemia-and-hyperglycemia-in-rats-induced-by-a-high-fat-and-fructose-diet
#18
Bo Chen, Piaopiao Long, Yue Sun, Qilu Meng, Xingxun Liu, Huanhuan Cui, Qingya Lv, Liang Zhang
In this study, the inhibitory effects of loquat leaf extract (LLE) on pancreatic α-amylase and α-glucosidase, and the preventative effects of LLE on hyperlipidemia and hyperglycemia in rats induced by a high fat and fructose diet have been evaluated. The LLE was chemically described using a high performance liquid chromatography-diode array detector coupled with a mass spectrometer (HPLC-DAD-MS/MS). 20 compounds including phenolic acids, flavonoids and triterpene acids were tentatively identified with authentic compounds or by referring to published articles and accessible databases (e...
January 26, 2017: Food & Function
https://www.readbyqxmd.com/read/28099250/interleukin-36%C3%AE-induces-inflammatory-mediators-from-human-pancreatic-myofibroblasts-via-a-myd88-dependent-pathway
#19
Atsushi Nishida, Osamu Inatomi, Takehide Fujimoto, Hirotsugu Imaeda, Masaji Tani, Akira Andoh
OBJECTIVES: Interleukin-36 (IL-36) is a recently described proinflammatory cytokine, characterized by the induction of inflammatory mediators. In the present study, we investigated the biological activity and the signal transduction of IL-36α in human pancreatic myofibroblasts. METHODS: The mRNA and protein expression of inflammatory mediators was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of IL-36α and its receptor in the pancreatic tissue was evaluated using immunohistochemical technique...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28062577/overlapping-specificity-of-duplicated-human-pancreatic-elastase-3-isoforms-and-archetypal-porcine-elastase-1-provides-clues-to-evolution-of-digestive-enzymes
#20
Eszter Boros, András Szabó, Katalin Zboray, Dávid Héja, Gábor Pál, Miklós Sahin-Tóth
Chymotrypsin-like elastases (CELAs) are pancreatic serine proteinases that digest dietary proteins. CELAs are typically expressed in multiple isoforms that can vary among different species. The human pancreas does not express CELA1 but secretes two CELA3 isoforms, CELA3A and CELA3B. The reasons for the CELA3 duplication and the substrate preferences of the duplicated isoforms are unclear. Here, we tested whether CELA3A and CELA3B evolved unique substrate specificities to compensate for the loss of CELA1. We constructed a phage library displaying variants of the substrate-like Schistocerca gregaria proteinase inhibitor 2 (SGPI-2) to select reversible high affinity inhibitors of human CELA3A, CELA3B, and porcine CELA1...
February 17, 2017: Journal of Biological Chemistry
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