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Pancreatic enzyme inhibitor

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https://www.readbyqxmd.com/read/29626120/a-new-method-for-tumor-imaging-by-targeting-cancer-associated-fibroblasts
#1
Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand, Uwe Haberkorn
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts (CAFs), which are present in more than 90% of epithelial carcinomas including pancreatic, colon and breast cancer. CAFs feature a high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but associated with a poor prognosis in cancer patients...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#2
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29606349/angiogenin-ribonuclease-5-is-an-egfr-ligand-and-a-serum-biomarker-for-erlotinib-sensitivity-in-pancreatic-cancer
#3
Ying-Nai Wang, Heng-Huan Lee, Chao-Kai Chou, Wen-Hao Yang, Yongkun Wei, Chun-Te Chen, Jun Yao, Jennifer L Hsu, Cihui Zhu, Haoqiang Ying, Yuanqing Ye, Wei-Jan Wang, Seung-Oe Lim, Weiya Xia, How-Wen Ko, Xiuping Liu, Chang-Gong Liu, Xifeng Wu, Huamin Wang, Donghui Li, Laura R Prakash, Matthew H Katz, Yaan Kang, Michael Kim, Jason B Fleming, David Fogelman, Milind Javle, Anirban Maitra, Mien-Chie Hung
Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin [ANG]) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment...
March 29, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29594979/anti-inflammatory-and-antioxidant-effects-of-captopril-compared-to-methylprednisolone-in-l-arginine-induced-acute-pancreatitis
#4
Nahla E El-Ashmawy, Naglaa F Khedr, Hoda A El-Bahrawy, Omnia B Hamada
BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease mediated by damage in acinar cells and pancreatic inflammation with infiltration of leukocytes. The pancreatic renin-angiotensin system may play an important role in the pathogenesis of AP. AIM: The present study aimed to investigate the possible protective role of captopril (CAP), an angiotensin-converting enzyme inhibitor, in attenuating L-arginine-induced AP rat model and to elucidate the underlying molecular mechanisms...
March 29, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29582334/acquired-hemophilia-a-associated-with-autoimmune-pancreatitis-with-serum-igg4-elevation
#5
Taisuke Narazaki, Shojiro Haji, Yasuhiro Nakashima, Yasuhiro Tsukamoto, Mariko Tsuda, Akiko Takamatsu, Hirofumi Ohno, Takamitsu Matsushima, Tomoko Matsumoto, Keiji Nogami, Midori Shima, Motoaki Shiratsuchi, Yoshihiro Ogawa
A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in 2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She suddenly presented with subcutaneous bleeding in 2015. Her activated partial thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was 290 BU/mL...
March 26, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29575187/culex-pipiens-sperm-motility-is-initiated-by-a-trypsin-like-protease-from-male-accessory-glands
#6
Kimberly Stephens, Richard A Cardullo, Catherine D Thaler
In most animals, sperm are stored in a quiescent state in the male reproductive tract and only initiate motility when released into either the female reproductive tract, or, in the case of broadcast spawners, the external environment. Male accessory gland secretions transferred into the female reproductive tract may provide factors that modulate sperm viability and storage, or aid in sperm competition, as well as activate sperm motility. In several insects, serine proteases have been implicated in activating sperm motility...
March 24, 2018: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29574296/novel-prodrug-prx-p4-003-selectively-activated-by-gut-enzymes-may-reduce-the-risk-of-iatrogenic-addiction-and-abuse
#7
Sandeep T Patil, Ron H Bihovsky, Steven A Smith, William Z Potter, Valentino J Stella
OBJECTIVES: Prescription stimulants are vulnerable to oral and parenteral abuse. Intravenous forms of abuse may be most detrimental due to an enhanced risk of dependence, overdose, and infectious diseases. Our objective was to discover an orally active prodrug of a stimulant that would not be easily converted to its parent when injected, thus hindering intravenous abuse. METHODS: Following an initial analysis of stimulant structures, the fencamfamine isomer [(-)-FCF; (N-ethyl-3-phenylbicyclo[2...
March 2, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29573125/risk-of-dipeptidyl-peptidase-4-dpp-4-inhibitors-on-site-specific-cancer-a-systematic-review-and-meta-analysis
#8
REVIEW
Jetty A Overbeek, Marina Bakker, Amber A W A van der Heijden, Myrthe P P van Herk-Sukel, Ron M C Herings, Giel Nijpels
BACKGROUND: The long-term impact of DPP-4 inhibition is unknown and there are concerns about the influence of DPP-4 inhibition on carcinogenesis of the pancreas and thyroid. As DPP-4 is a rather unselective enzyme present in many tissues, we focused on all specific cancer types. METHODS: PubMed and EMBASE were searched between Jan 2005 and Apr 2017 to identify studies comparing DPP-4 inhibitors with either placebo or active drugs on cancer risk. Studies were included if they reported on at least one specific cancer outcome and had a follow-up of at least one year after start of drug use...
March 23, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29520731/individualization-of-irinotecan-treatment-a-review-of-pharmacokinetics-pharmacodynamics-and-pharmacogenetics
#9
REVIEW
Femke M de Man, Andrew K L Goey, Ron H N van Schaik, Ron H J Mathijssen, Sander Bins
Since its clinical introduction in 1998, the topoisomerase I inhibitor irinotecan has been widely used in the treatment of solid tumors, including colorectal, pancreatic, and lung cancer. Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability. Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself. Several phase I and II enzymes, including cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A, are involved in the formation of inactive metabolites, making its metabolism prone to environmental and genetic influences...
March 8, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29506517/rhaponticum-acaule-l-dc-essential-oil-chemical-composition-in-vitro-antioxidant-and-enzyme-inhibition-properties
#10
Habib Mosbah, Hassiba Chahdoura, Jannet Kammoun, Malek Besbes Hlila, Hanen Louati, Saoussen Hammami, Guido Flamini, Lotfi Achour, Boulbaba Selmi
BACKGROUND: α-glucosidase is a therapeutic target for diabetes mellitus (DM) and α-glucosidase inhibitors play a vital role in the treatments for the disease. Furthermore, xanthine oxidase (XO) is a key enzyme that catalyzes hypoxanthine and xanthine to uric acid which at high levels can lead to hyperuricemia which is an important cause of gout. Pancreatic lipase (PL) secreted into the duodenum plays a key role in the digestion and absorption of fats. For its importance in lipid digestion, PL represents an attractive target for obesity prevention...
March 5, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29502987/the-prevalence-of-small-intestinal-bacterial-overgrowth-in-non-surgical-patients-with-chronic-pancreatitis-and-pancreatic-exocrine-insufficiency-pei
#11
Hazel M Ní Chonchubhair, Yasir Bashir, Mark Dobson, Barbara M Ryan, Sinead N Duggan, Kevin C Conlon
BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates...
February 24, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29486665/mirtazapine-induced-pancreatitis-a-case-report
#12
Riley D Bowers, Sara M Valanejad, Ashley A Holombo
Acute pancreatitis has numerous etiologies, with the most common including gallstones, alcohol abuse, and medications such as angiotensin-converting enzyme (ACE) inhibitors, statins, and diuretics. Mirtazapine has been associated with increased serum cholesterol and serum triglyceride levels. However, few studies have reported dangerously elevated triglyceride levels resulting in acute pancreatitis. This report discusses a case of mirtazapine-induced pancreatitis in a 46-year-old African American female. The patient presented to the emergency department with pancreatitis, presumably alcohol-induced as with a prior admission, but she denied any recent alcohol use...
January 1, 2018: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29463644/the-inositol-requiring-enzyme-1-ire1%C3%AE-rnase-inhibitor-4%C3%A2%C2%B58c-is-also-a-potent-cellular-antioxidant
#13
Stanley M H Chan, Mark P Lowe, Ashton Bernard, Alyson A Miller, Terence P Herbert
Inositol Requiring Enzyme 1 alpha (IRE1α) is an ER-transmembrane endonuclease that is activated in response to ER stress as part of the unfolded protein response (UPR). Chronic activation of the UPR has been implicated in the pathogenesis of many common disease including diabetes, cancer and neurological pathologies such as Huntington's and Alzheimer's disease. 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde (4µ8C) is widely used as a specific inhibitor of IRE1α ribonuclease activity in mechanistic studies (IC50 of 6...
February 20, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29462900/next-generation-immunotherapy-for-pancreatic-cancer-dna-vaccination-is-seeking-new-combo-partners
#14
REVIEW
Paola Cappello, Claudia Curcio, Giorgia Mandili, Cecilia Roux, Sara Bulfamante, Francesco Novelli
Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor...
February 16, 2018: Cancers
https://www.readbyqxmd.com/read/29451201/tackling-dipeptidyl-peptidase-iv-in-neurological-disorders
#15
REVIEW
Ghaith Al-Badri, Gian Marco Leggio, Giuseppe Musumeci, Rubina Marzagalli, Filippo Drago, Alessandro Castorina
Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide (GIP), three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449808/suppressive-effects-of-clerodendrum-volubile-p-beauv-labiatae-methanolic-extract-and-its-fractions-on-type-2-diabetes-and-its-complications
#16
Ochuko L Erukainure, Rahman M Hafizur, Nurul Kabir, M Iqbal Choudhary, Olubunmi Atolani, Priyanka Banerjee, Robert Preissner, Chika I Chukwuma, Aliyu Muhammad, Eric O Amonsou, Md Shahidul Islam
Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions of Clerodendrum volubile leaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca 2+ levels, and β-cell distribution and function...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29423062/drug-induced-ciliogenesis-in-pancreatic-cancer-cells-is-facilitated-by-the-secreted-atp-purinergic-receptor-signaling-pathway
#17
Niamat Ali Khan, Abhishek D Garg, Patrizia Agostinis, Johannes V Swinnen
Malignant transformation of cells is often accompanied by the loss of the primary cilium, a protruding microtubule-based sensory organelle, suggesting that it plays an "onco-suppressive" role. Therefore, restoration of the primary cilium is being explored as a new therapeutic approach to attenuate tumor growth. Recently, several commonly used chemotherapeutic drugs have been identified to induce the primary cilium in pancreatic cancer cells. The mechanisms by which these drugs re-express the cilium remain, however, enigmatic...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412816/tissue-expression-of-dpp-iv-in-obesity-diabetes-and-modulatory-effects-on-peptide-regulation-of-insulin-secretion
#18
Aine M McKillop, Claire L Stevenson, Brian M Moran, Yasser H A Abdel-Wahab, Peter R Flatt
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < ...
February 2018: Peptides
https://www.readbyqxmd.com/read/29402301/sialylation-of-egfr-by-the-st6gal-i-sialyltransferase-promotes-egfr-activation-and-resistance-to-gefitinib-mediated-cell-death
#19
Colleen M Britain, Andrew T Holdbrooks, Joshua C Anderson, Christopher D Willey, Susan L Bellis
BACKGROUND: The ST6Gal-I sialyltransferase is upregulated in numerous cancers, and high expression of this enzyme correlates with poor patient prognosis in various malignancies, including ovarian cancer. Through its sialylation of a select cohort of cell surface receptors, ST6Gal-I modulates cell signaling to promote tumor cell survival. The goal of the present study was to investigate the influence of ST6Gal-I on another important receptor that controls cancer cell behavior, EGFR. Additionally, the effect of ST6Gal-I on cancer cells treated with the common EGFR inhibitor, gefitinib, was evaluated...
February 5, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29383542/ulinastatin-protects-against-cvb3-induced-acute-viral-myocarditis-through-nrf2-activation
#20
Fangqiang Song, Fanpo Kong, Hongqing Zhang, Yongqin Zhou, Ming Li
Inflammation and oxidative stress are implicated in the pathogenesis of acute viral myocarditis (AVM). Ulinastantin (UTI), an inhibitor of serine protease widely used in treatment of pancreatitis and various inflammatory disorders, displays cardioprotective properties in experimental animals. Although the specific mechanism through which UTI regulates cardiac function is not well explored, evidence suggests that UTI might activate nuclear factor E2-related factor 2 (Nrf2) signaling. In this study, we investigated the role of Nrf2 in mediating UTI's cardioprotection in a mouse model of AVM...
January 30, 2018: Inflammation
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