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Proton pump inhibition

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https://www.readbyqxmd.com/read/28938598/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#1
Xiaoyu Wang, Chun Liu, Jiaqi Wang, Yue Fan, Zhenghua Wang, Yuanyuan Wang
Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937021/optimized-high-dose-amoxicillin-proton-pump-inhibitor-dual-therapies-fail-to-achieve-high-cure-rates-in-china
#2
Jia-Li Hu, Jun Yang, Yin-Bin Zhou, Ping Li, Ran Han, Dian-Chun Fang
Background\Aim: Quadruple daily administration of proton-pump inhibitor (PPI) therapy achieves potent acid inhibition, and combined with amoxicillin, with its pharmacodynamic and pharmacokinetic characteristics, may be efficient for Helicobacter pylori eradication. We compared the efficacy of two optimized high-dose dual therapies with a bismuth-containing quadruple regimen for treating H. pylori infection. Rabeprazole dosages for H. pylori eradication were also evaluated. PATIENTS AND METHODS: Treatment-naive and H...
September 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28926955/identification-of-novel-bisbenzimidazole-derivatives-as-anticancer-vacuolar-h%C3%A2-%C2%BA-atpase-inhibitors
#3
Renukadevi Patil, Arpita Kulshrestha, Anjali Tikoo, Sara Fleetwood, Gajendra Katara, Bala Kolli, William Seibel, Alice Gilman-Sachs, Shivaputra A Patil, Kenneth D Beaman
The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (V) as an initial hit from a similarity search using four known V-ATPase inhibitors (I-IV)...
September 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28911053/co-ordination-of-ndh-and-cup-proteins-in-co2-uptake-in-cyanobacterium-synechocystis-sp-pcc-6803
#4
Xunling Han, Nan Sun, Min Xu, Hualing Mi
High and low affinity CO2-uptake systems containing CupA (NDH-1MS) and CupB (NDH-1MS'), respectively, have been identified in Synechocystis sp. PCC 6803, but it is yet unknown how the complexes function in CO2 uptake. In this work, we found that deletion of cupB significantly lowered the growth of cells, and deletion of both cupA and cupB seriously suppressed the growth below pH 7.0 even under 3% CO2. The rate of photosynthetic oxygen evolution was decreased slightly by deletion of cupA but significantly by deletion of cupB and more severely by deletion of both cupA and cupB, especially in response to changed pH conditions under 3% CO2...
June 1, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28902909/the-cytoprotective-protein-clusterin-is-overexpressed-in-hypergastrinemic-rodent-models-of-oxyntic-preneoplasia-and-promotes-gastric-cancer-cell-survival
#5
Pål Vange, Torunn Bruland, Berit Doseth, Reidar Fossmark, Mirta M L Sousa, Vidar Beisvag, Øystein Sørdal, Gunnar Qvigstad, Helge L Waldum, Arne K Sandvik, Ingunn Bakke
The cytoprotective protein clusterin is often dysregulated during tumorigenesis, and in the stomach, upregulation of clusterin marks emergence of the oxyntic atrophy (loss of acid-producing parietal cells)-associated spasmolytic polypeptide-expressing metaplasia (SPEM). The hormone gastrin is important for normal function and maturation of the gastric oxyntic mucosa and hypergastrinemia might be involved in gastric carcinogenesis. Gastrin induces expression of clusterin in adenocarcinoma cells. In the present study, we examined the expression patterns and gastrin-mediated regulation of clusterin in gastric tissue from: humans; rats treated with proton pump (H+/K+-ATPase) inhibitors and/or a gastrin receptor (CCK2R) antagonist; H+/K+-ATPase β-subunit knockout (H/K-β KO) mice; and Mongolian gerbils infected with Helicobacter pylori and given a CCK2R antagonist...
2017: PloS One
https://www.readbyqxmd.com/read/28894571/vonoprazan-10-mg-daily-is-effective-for-the-treatment-of-patients-with-proton-pump-inhibitor-resistant-gastroesophageal-reflux-disease
#6
Satoshi Shinozaki, Hiroyuki Osawa, Yoshikazu Hayashi, Hirotsugu Sakamoto, Yasutoshi Kobayashi, Alan Kawarai Lefor, Hironori Yamamoto
Gastroesophageal reflux disease (GERD) is commonly treated by primary care physicians. Although proton pump inhibitors (PPI) have been the mainstay of GERD treatment for two decades, in some patients GERD is refractory to standard dose PPI for more than eight weeks and is referred to as PPI-resistant GERD. Vonoprazan, a novel competitive acid blocker, became available in Japan for the treatment of patients with GERD, and has greater acid inhibition than existing PPIs. The aim of the present study was to determine the effect of vonoprazan 10 mg daily on PPI-resistant GERD...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28880991/a-comparison-of-alkaline-water-and-mediterranean-diet-vs-proton-pump-inhibition-for-treatment-of-laryngopharyngeal-reflux
#7
Craig H Zalvan, Shirley Hu, Barbara Greenberg, Jan Geliebter
Importance: Laryngopharyngeal reflux (LPR) is a common disorder with protean manifestations in the head and neck. In this retrospective study, we report the efficacy of a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions compared with that of the traditional treatment approach of proton pump inhibition (PPI) and standard reflux precautions. Objective: To determine whether treatment with a diet-based approach with standard reflux precautions alone can improve symptoms of LPR compared with treatment with PPI and standard reflux precautions...
September 7, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28866861/effects-of-the-proton-pump-inhibitors-omeprazole-and-pantoprazole-on-the-cytochrome-p450-mediated-metabolism-of-venlafaxine
#8
Maxim Kuzin, Georgios Schoretsanitis, Ekkehard Haen, Benedikt Stegmann, Christoph Hiemke, Gerhard Gründer, Michael Paulzen
BACKGROUND AND OBJECTIVE: An increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine. METHODS: A therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40)...
September 2, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28861639/repositioning-of-proton-pump-inhibitors-in-cancer-therapy
#9
REVIEW
Zhen-Ning Lu, Bing Tian, Xiu-Li Guo
Drug repositioning, as a smart way to exploit new molecular targets of a known drug, has been gaining increasing attention in the discovery of anti-cancer drugs. Proton pump inhibitors (PPIs) as benzimidazole derivatives, which are essentially H(+)-K(+)-ATPases inhibitors, are commonly used in the treatment of acid-related diseases such as gastric ulcer. In recent years, exploring the new application of PPIs in anti-cancer field has become a hot research topic. Interestingly, cancer cells display an alkaline intracellular pH and an acidic extracellular pH...
August 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28860418/pantoprazole-a-proton-pump-inhibitor-does-not-prevent-botulinum-toxin-induced-disuse-osteopenia-in-mice
#10
J B Vegger, A Brüel, J S Thomsen
OBJECTIVES: Pantoprazole is a proton pump inhibitor that has been shown to inhibit bone resorption. The aim of the study was to investigate whether pantoprazole can prevent development of botulinum toxin (BTX)-induced disuse osteopenia in mice. METHODS: Forty-eight 16-week-old female C57BL/6J mice were randomized into 4 groups (n=12): Base, Ctrl, BTX, and BTX+Pan. The Base group was euthanized at study start. The BTX and BTX+Pan groups were immobilized by injections with BTX in one hind limb...
September 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28835017/cariporide-enhances-the-dna-damage-and-apoptosis-in-acid-tolerable-malignant-mesothelioma-h-2452-cells
#11
Yoon-Jin Lee, Jin-Ho Bae, Soo-A Kim, Sung-Ho Kim, Kee-Min Woo, Hae-Seon Nam, Moon-Kyun Cho, Sang-Han Lee
The Na(+)/H(+) exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular Na(+) and the extrusion of intracellular H(+). The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent Na(+)/H(+)-exchange inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells...
August 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28815028/the-majority-of-hepatitis-c-patients-treated-with-direct-acting-antivirals-are-at-risk-for-relevant-drug-drug-interactions
#12
Elise J Smolders, Floor Ac Berden, Clara Tmm de Kanter, Wietske Kievit, Joost Ph Drenth, David M Burger
BACKGROUND: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions. OBJECTIVE: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients. METHODS: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28808054/mst4-phosphorylates-acap4-to-orchestrate-apical-membrane-remodeling-during-gastric-acid-secretion
#13
Xiao Yuan, Phil Y Yao, Jiying Jiang, Yin Zhang, Zeqi Su, Wendy Yao, Xueying Wang, Ping Gui, McKay Mullen, Calmour Henry, Tarsha Ward, Wenwen Wang, Larry Brako, Ruijun Tian, Xuannv Zhao, Fengsong Wang, Xinwang Cao, Dongmei Wang, Xing Liu, Xia Ding, Xuebiao Yao
The digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion (Jiang et al., 2015. J. Biol. Chem. 290, 28272-28285). However, it remains uncharacterized how PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28801980/effects-of-proton-pump-inhibitors-and-famotidine-on-elimination-of-plasma-methotrexate-evaluation-of-drug-drug-interactions-mediated-by-organic-anion-transporter-3
#14
Katsuya Narumi, Yu Sato, Masaki Kobayashi, Ayako Furugen, Kumiko Kasashi, Takehiro Yamada, Takanori Teshima, Ken Iseki
Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyze the potential drug-drug interactions between MTX and gastric antisecretory drugs in high-dose MTX (HD-MTX) therapy. We retrospectively analyzed the impact of PPIs on the plasma MTX concentration on 73 cycles of HD-MTX therapy performed in 43 patients...
August 12, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28775146/inhibition-of-the-v-atpase-by-archazolid-a-a-new-strategy-to-inhibit-emt
#15
Henriette Merk, Philipp Messer, Maximilian A Ardelt, Don C Lamb, Stefan Zahler, Rolf Müller, Angelika M Vollmar, Johanna Pachmayr
Epithelial-mesenchymal transition (EMT) induces tumor-initiating cells (TICs) which account for tumor recurrence, metastasis and therapeutic resistance. Strategies to interfere with EMT are rare but urgently needed to improve cancer therapy. By using the myxobacterial natural compound Archazolid A as a tool, we elucidate the V-ATPase, a multimeric proton pump that regulates lysosomal acidification, as a crucial player in EMT and identify the inhibition of V-ATPase by Archazolid A as promising strategy to block EMT...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28761572/a-case-of-severe-iron-deficiency-anemia-associated-with-long-term-proton-pump-inhibitor-use
#16
REVIEW
David N Dado, Erin B Loesch, Sudha P Jaganathan
The use of proton pump inhibitors (PPIs) in the treatment of gastrointestinal diseases has evolved over recent years. Initially intended for short-term use, PPIs are increasingly being used, often inappropriately, as long-term maintenance medications. The mechanism of action of PPIs is suppression of gastric basal and stimulated acid secretion by inhibiting the parietal cell H(+)/K(+) ATP pump with a resultant increase in gastric pH and hypo- or achlorhydria. Although short-term use is related to few adverse effects, long-term use is associated with numerous complications...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28752076/molecular-machineries-of-ph-dysregulation-in-tumor-microenvironment-potential-targets-for-cancer-therapy
#17
REVIEW
Mohammad Reza Asgharzadeh, Jaleh Barar, Mohammad M Pourseif, Morteza Eskandani, Mojtaba Jafari Niya, Mohammad Reza Mashayekhi, Yadollah Omidi
Introduction: Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. Methods: In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28749956/functional-characterization-of-sodium-pumping-rhodopsins-with-different-pumping-properties
#18
Satoshi P Tsunoda, Matthias Prigge, Rei Abe-Yoshizumi, Keiichi Inoue, Yuko Kozaki, Toru Ishizuka, Hiromu Yawo, Ofer Yizhar, Hideki Kandori
Sodium pumping rhodopsins (NaRs) are a unique member of the microbial-type I rhodopsin family which actively transport Na+ and H+ depending on ionic condition. In this study, we surveyed 12 different NaRs from various sources of eubacteria for their electrophysiological as well as spectroscopic properties. In mammalian cells several of these NaRs exhibited a Na+ based pump photocurrent and four interesting candidates were chosen for further characterization. Voltage dependent photocurrent amplitudes revealed a membrane potential-sensitive turnover rate, indicating the presence of an electrically-charged intermediate(s) in the photocycle reaction...
2017: PloS One
https://www.readbyqxmd.com/read/28748627/genetic-ablation-of-carbonic-anhydrase-ix-disrupts-gastric-barrier-function-via-claudin-18-downregulation-and-acid-backflux
#19
Taolang Li, Xuemei Liu, Brigitte Riederer, Katerina Nikolovska, Anurag Kumar Singh, Kari A Mäkelä, Anna Seidler, Yongjian Liu, Gerolf Gros, Helmut Bartels, Karl Heinz Herzig, Ursula Seidler
AIM: The study aims to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX knockout and WT gastric surface epithelial cells to withstand luminal acid load by measuring the pHi of exteriorized gastric mucosa in vivousing two photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analyzed by RT-PCR...
July 27, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28747707/the-cryo-em-structure-of-gastric-h-k-atpase-with-bound-byk99-a-high-affinity-member-of-k-competitive-imidazo-1-2-a-pyridine-inhibitors
#20
Kazuhiro Abe, Jun Shimokawa, Mao Naito, Keith Munson, Olga Vagin, George Sachs, Hiroshi Suzuki, Kazutoshi Tani, Yoshinori Fujiyoshi
The gastric proton pump H(+),K(+)-ATPase acidifies the gastric lumen, and thus its inhibitors, including the imidazo[1,2-a]pyridine class of K(+)-competitive acid blockers (P-CABs), have potential application as acid-suppressing drugs. We determined the electron crystallographic structure of H(+),K(+)-ATPase at 6.5 Å resolution in the E2P state with bound BYK99, a potent P-CAB with a restricted ring structure. The BYK99 bound structure has an almost identical profile to that of a previously determined structure with bound SCH28080, the original P-CAB prototype, but is significantly different from the previously reported P-CAB-free form, illustrating a common conformational change is required for P-CAB binding...
July 26, 2017: Scientific Reports
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