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Pancreatic enzyme inhibitor

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https://www.readbyqxmd.com/read/27904116/symptomatic-acute-pancreatitis-induced-by-nilotinib-a-report-of-two-cases
#1
Toshiki Yamada, Yasuhito Nannya, Masahito Shimizu, Mitsuru Seishima, Hisashi Tsurumi
Nilotinib is a selective tyrosine kinase inhibitor for the treatment of Philadelphia chromosome-positive leukemias. An elevation of the pancreatic enzyme level is one of the major adverse events associated with nilotinib, but whether or not nilotinib induces symptomatic pancreatitis remains to be elucidated. The cases of two chronic myeloid leukemia patients treated with nilotinib who developed symptomatic acute pancreatitis on the third and fifth day of nilotinib administration are herein presented. Since both patients had no other etiologies for pancreatitis, nilotinib was considered to be the causal agent...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27846200/the-use-of-drugs-acting-on-the-renin-angiotensin-system-and-the-incidence-of-pancreatic-cancer
#2
Victoria Mandilaras, Nathaniel Bouganim, Hui Yin, Jamil Asselah, Laurent Azoulay
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Thus, the objective of this study was to determine whether the use of ACEIs and/or ARBs is associated with a decreased risk of pancreatic cancer. METHODS: We conducted a population-based cohort study, using a nested case-control analysis within the UK Clinical Practice Research Datalink population...
November 15, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27836541/substituted-e-2-2-benzylidenehydrazinyl-4-methylthiazole-5-carboxylates-as-dual-inhibitors-of-15-lipoxygenase-carbonic-anhydrase-ii-synthesis-biological-evaluation-and-docking-studies
#3
Aamer Saeed, Shafi Ullah Khan, Parvez Ali Mahesar, Pervaiz Ali Channar, Ghulam Shabir, Jamshed Iqbal
15-Lipoxygenase (15-LOX) plays a major role in many inflammatory lung diseases including chronic obstructive pulmonary disease (COPD), asthma and chronic bronchitis. Over-expression of 15-LOX is related with some specific carcinomas including pancreatic, gastric and brain tumor. Similarly among different isozymes of carbonic anhydrase (CA), CA II is expressed in pancreatic, gastric carcinomas as well as in brain tumors. Therefore, novel potent inhibitors of both 15-LOX and CA II are required to explore the role of these enzymes further and to enable the drug discovery efforts...
November 8, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27825371/effective-and-safe-proton-pump-inhibitor-therapy-in-acid-related-diseases-a-position-paper-addressing-benefits-and-potential-harms-of-acid-suppression
#4
EDITORIAL
Carmelo Scarpignato, Luigi Gatta, Angelo Zullo, Corrado Blandizzi
BACKGROUND: The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions...
November 9, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27793122/acute-pancreatitis-associated-with-everolimus-after-kidney-transplantation-a-case-report
#5
Francesco Fontana, Gianni Cappelli
BACKGROUND: Acute pancreatitis (AP) following KT is a rare and often fatal complication of the early post-transplant period. Common causative factors for AP are rare after KT; anti-rejection drugs as CyA, prednisone and MMF have been implicated, although evidence is not strong and we found no reports on possible causative role for mTOR inhibitors. CASE PRESENTATION: A 55-year-old Caucasian man with end-stage renal disease due to idiopathic membrano-prolipherative glomerulonephritis underwent single kidney transplantation (KT) from cadaveric donor...
October 28, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27779720/pace4-regulates-apoptosis-in-human-pancreatic-cancer-panc%C3%A2-1-cells-via-the-mitochondrial-signaling-pathway
#6
Xiao-Feng Tian, Guo-Min Huang, Hong-Liang Zang, Hong Cao
Previous studies have demonstrated the overexpression of paired basic amino acid cleaving enzyme 4 (PACE4) mRNA in prostate cancer tissues. This overexpression is correlated with higher circulating protein levels in certain patients, however, the role of PACE4 in apoptosis and the potential molecular mechanisms of pancreatic cancer remain to be elucidated. The aim of the present study was to investigate the effect and potential molecular mechanisms of PACE4 on apoptosis in the Panc‑1 pancreatic cancer cell line...
October 25, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27778022/upregulation-of-cystathionine-%C3%AE-synthetase-in-the-arcuate-nucleus-produces-pain-hypersensitivity-via-pkc-upregulation-and-glun2b-phosphorylation-in-rats-with-chronic-pancreatitis
#7
Hang Zheng, Hong-Yan Zhu, Xiao-Yu Zhang, Meng Wang, Ying Xiao, Guang-Yin Xu, Xing-Hong Jiang
Hydrogen sulfide (H2S) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of H2S and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27750213/acetyl-coa-carboxylase-inhibitors-attenuate-wnt-and-hedgehog-signaling-and-suppress-pancreatic-tumor-growth
#8
Elissaveta Petrova, Arne Scholz, Juliane Paul, Andrea Sturz, Katja Haike, Franziska Siegel, Dominik Mumberg, Ningshu Liu
Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in de novo fatty acid synthesis, and its ACC1 isoform is overexpressed in pancreatic and various other cancers. The activity of many oncogenic signaling molecules, including WNT and Hedgehog (HH), is post-translationally modified by lipidation. Here, we report that inhibition of ACC by a small molecule inhibitor, BAY ACC002, blocked WNT3A lipidation, secretion, and signaling. In pancreatic cancer cells, where WNT and HH are key oncogenic drivers, ACC inhibition simultaneously suppressed WNT and HH signaling, and led to anti-proliferative effects...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27745548/enzyme-driven-chemo-and-radiation-therapy-with-12-pyrimidine-nucleoside-analogs-not-yet-in-the-clinic
#9
Sheldon Greer, Tieran Han, Cristina Dieguez, Nicola McLean, Rafael Saer, Isildinha Reis, Joe Levi, Victor E Marquez
Enzymatic activity from tumor and adjacent normal tissue of 200 patients involving deoxycytidine kinase (dCK), uridine/cytidine kinase (U/CK), cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD) was quantified. . Patients with brain (17), colon (24), and breast (30) tumors, 53, 67, and 73%, respectively, had an elevated T/N value (Specific Activity of tumor/ Specific Activity of normal tissue) involving dCK and dCMPD suggesting chemo therapy with 5-fluorodeoxycytidine (5-FdC) alone or in combination with thymidine plus deoxytetrahydrouridine, or with the radiosensitizer, 5-chlorodeoxycytidine (5-CldC) plus tetrahydrouridine (H4U)...
October 13, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27739027/an-indispensable-role-of-cpt-1a-to-survive-cancer-cells-during-energy-stress-through-rewiring-cancer-metabolism
#10
Jingtao Luo, Yun Hong, Xiaoan Tao, Xi Wei, Lun Zhang, Qiang Li
Unlike normal cells, cancer cells are recently identified to rely on aerobic glycolysis for energy production called the Warburg effect. Several attempts are being made to target this metabolic reprogramming pathway in treating cancers; however, the successful rate is very limited. In this study, we investigated the functional roles of fatty acid oxidation key enzyme carnitine palmitoyl transferase 1a (CPT-1a), during the metabolic programming of pancreatic ductal adenocarcinoma (PDAC) cells induced by glucose deprivation...
October 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27708394/fragment-based-de-novo-design-of-a-cystathionine-%C3%AE-lyase-selective-inhibitor-blocking-hydrogen-sulfide-production
#11
Angela Corvino, Beatrice Severino, Ferdinando Fiorino, Francesco Frecentese, Elisa Magli, Elisa Perissutti, Vincenzo Santagada, Mariarosaria Bucci, Giuseppe Cirino, Geoff Kelly, Luigi Servillo, Grzegorz Popowicz, Annalisa Pastore, Giuseppe Caliendo
Hydrogen sulfide is an essential catabolite that intervenes in the pathophysiology of several diseases from hypertension to stroke, diabetes and pancreatitis. It is endogenously synthesized mainly by two pyridoxal-5'-phosphate-dependent enzymes involved in L-cysteine metabolism: cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). Research in this field is currently impaired by the lack of pharmacological tools such as selective enzymatic inhibitors that could target specifically only one of these pathways...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27663206/antiobesity-and-antihyperglycaemic-effects-of-adiantum-capillus-veneris-extracts-in-vitro-and-in-vivo-evaluations
#12
Violet Kasabri, Entisar K Al-Hallaq, Yasser K Bustanji, Khalid K Abdul-Razzak, Ismail F Abaza, Fatma U Afifi
CONTEXT: Adiantum capillus-veneris L. (Adiantaceae) hypocholesterolemic activity is therapeutically praised. OBJECTIVES: Pharmacological modulation of pancreatic triacylglycerol lipase (PL) and α-amylase/α-glucosidase by A. capillus-veneris are evaluated. MATERIALS AND METHODS: Using positive controls (acarbose, orlistat, guar gum, atorvastatin, glipizide and metformin) as appropriate, crude aqueous extracts (AEs) of A. capillus-veneris aerial parts were tested via a combination of in vitro enzymatic (0...
September 23, 2016: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27637085/dual-oxidase2-and-pancreatic-adenocarcinoma-ifn-%C3%AE-mediated-dual-oxidase2-overexpression-results-in-h2o2-induced-erkassociated-up-regulation-of-hif-1%C3%AE-and-vegf-a
#13
Yongzhong Wu, Jennifer L Meitzler, Smitha Antony, Agnes Juhasz, Jiamo Lu, Guojian Jiang, Han Liu, Melinda Hollingshead, Diana C Haines, Donna Butcher, Michaela S Panter, Krishnendu Roy, James H Doroshow
Several NADPH oxidase family members, including dual oxidase 2 [DUOX2], are expressed in human tumors, particularly gastrointestinal cancers associated with long-standing chronic inflammation. We found previously that exposure of pancreatic ductal adenocarcinoma cells to the pro-inflammatory cytokine IFN-γ increased DUOX2 expression (but not other NADPH oxidases) leading to long-lived H2O2 production. To elucidate the pathophysiology of DUOX2-mediated H2O2 formation in the pancreas further, we demonstrate here that IFN-γ-treated BxPC-3 and CFPAC-1 pancreatic cancer cells (known to increase DUOX2 expression) produce significant levels of intracellular oxidants and extracellular H2O2 which correlate with concomitant up-regulation of VEGF-A and HIF-1α transcription...
September 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27617390/an-in-vivo-multiplexed-small-molecule-screening-platform
#14
Barbara M Grüner, Christopher J Schulze, Dian Yang, Daisuke Ogasawara, Melissa M Dix, Zoë N Rogers, Chen-Hua Chuang, Christopher D McFarland, Shin-Heng Chiou, J Mark Brown, Benjamin F Cravatt, Matthew Bogyo, Monte M Winslow
Phenotype-based small-molecule screening is a powerful method to identify molecules that regulate cellular functions. However, such screens are generally performed in vitro under conditions that do not necessarily model complex physiological conditions or disease states. Here, we use molecular cell barcoding to enable direct in vivo phenotypic screening of small-molecule libraries. The multiplexed nature of this approach allows rapid in vivo analysis of hundreds to thousands of compounds. Using this platform, we screened >700 covalent inhibitors directed toward hydrolases for their effect on pancreatic cancer metastatic seeding...
October 2016: Nature Methods
https://www.readbyqxmd.com/read/27614430/bis-acetylacetonato-oxidovanadium-iv-and-sodium-metavanadate-inhibit-cell-proliferation-via-ros-induced-sustained-mapk-erk-activation-but-with-elevated-akt-activity-in-human-pancreatic-cancer-aspc-1-cells
#15
Jing-Xuan Wu, Yi-Hua Hong, Xiao-Gai Yang
In this study, the antiproliferative effect of bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate and the underlying mechanisms were investigated in human pancreatic cancer cell line AsPC-1. The results showed that both exhibited an antiproliferative effect through inducing G2/M cell cycle arrest and can also cause elevation of reactive oxygen species (ROS) levels in cells. Moreover, the two vanadium compounds induced the activation of both PI3K/AKT and MAPK/ERK signaling pathways dose- and time-dependently, which could be counteracted with the antioxidant N-acetylcysteine...
September 10, 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27567377/bovine-pancreatic-trypsin-inhibitor-immobilized-onto-sepharose-as-a-new-strategy-to-purify-a-thermostable-alkaline-peptidase-from-cobia-rachycentron-canadum-processing-waste
#16
Renata Cristina da Penha França, Caio Rodrigo Dias Assis, Juliana Ferreira Santos, Ricardo José Soares Torquato, Aparecida Sadae Tanaka, Izaura Yoshico Hirata, Diego Magno Assis, Maria Aparecida Juliano, Ronaldo Olivera Cavalli, Luiz Bezerra de Carvalho, Ranilson Souza Bezerra
A thermostable alkaline peptidase was purified from the processing waste of cobia (Rachycentron canadum) using bovine pancreatic trypsin inhibitor (BPTI) immobilized onto Sepharose. The purified enzyme had an apparent molecular mass of 24kDa by both sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. Its optimal temperature and pH were 50°C and 8.5, respectively. The enzyme was thermostable until 55°C and its activity was strongly inhibited by the classic trypsin inhibitors N-ρ-tosyl-l-lysine chloromethyl ketone (TLCK) and benzamidine...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27559084/combination-therapy-with-bptes-nanoparticles-and-metformin-targets-the-metabolic-heterogeneity-of-pancreatic-cancer
#17
Amira Elgogary, Qingguo Xu, Brad Poore, Jesse Alt, Sarah C Zimmermann, Liang Zhao, Jie Fu, Baiwei Chen, Shiyu Xia, Yanfei Liu, Marc Neisser, Christopher Nguyen, Ramon Lee, Joshua K Park, Juvenal Reyes, Thomas Hartung, Camilo Rojas, Rana Rais, Takashi Tsukamoto, Gregg L Semenza, Justin Hanes, Barbara S Slusher, Anne Le
Targeting glutamine metabolism via pharmacological inhibition of glutaminase has been translated into clinical trials as a novel cancer therapy, but available drugs lack optimal safety and efficacy. In this study, we used a proprietary emulsification process to encapsulate bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a selective but relatively insoluble glutaminase inhibitor, in nanoparticles. BPTES nanoparticles demonstrated improved pharmacokinetics and efficacy compared with unencapsulated BPTES...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27557659/pigment-epithelium-derived-factor-pedf-blocks-wnt3a-protein-induced-autophagy-in-pancreatic-intraepithelial-neoplasms
#18
Jingjing Gong, Glenn Belinsky, Usman Sagheer, Xuchen Zhang, Paul J Grippo, Chuhan Chung
An increase in autophagy characterizes pancreatic carcinogenesis, but the signals that regulate this process are incompletely understood. Because canonical Wnt/β-catenin signaling is necessary for the transition from early to advanced pancreatic intraepithelial neoplasia (PanIN) lesions, we assessed whether Wnt ligands and endogenous inhibitors of Wnt signaling modulate autophagy. In this study, canonical Wnt3a ligand induced autophagy markers and vacuoles in murine PanIN cells. Furthermore, pigment epithelium-derived factor (PEDF), a secreted glycoprotein known for its anti-tumor properties, blocked Wnt3a-directed induction of autophagy proteins...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27533760/gliptins-and-their-target-dipeptidyl-peptidase-4-implications-for-the-treatment-of-vascular-disease
#19
REVIEW
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/27531902/the-histone-methyltransferase-g9a-as-a-therapeutic-target-to-override-gemcitabine-resistance-in-pancreatic-cancer
#20
Mei-Ren Pan, Ming-Chuan Hsu, Chi-Wen Luo, Li-Tzong Chen, Yan-Shen Shan, Wen-Chun Hung
Gemcitabine (GEM) resistance is a critical issue for pancreatic cancer treatment. The involvement of epigenetic modification in GEM resistance is still unclear. We established a GEM-resistant subline PANC-1-R from the parental PANC-1 pancreatic cancer cells and found the elevation of various chromatin-modifying enzymes including G9a in GEM-resistant cells. Ectopic expression of G9a in PANC-1 cells increased GEM resistance while inactivation of G9a in PANC-1-R cells reduced it. Challenge of PANC-1 cells with GEM increased the expression of stemness markers including CD133, nestin and Lgr5 and promoted sphere forming activity suggesting chemotherapy enriched cancer cells with stem-like properties...
August 12, 2016: Oncotarget
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