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Proton pump inhibitors and cancer

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https://www.readbyqxmd.com/read/28926955/identification-of-novel-bisbenzimidazole-derivatives-as-anticancer-vacuolar-h%C3%A2-%C2%BA-atpase-inhibitors
#1
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/28922414/a-nonrandomized-trial-of-vitamin-d-supplementation-for-barrett-s-esophagus
#2
Linda C Cummings, Prashanthi N Thota, Joseph E Willis, Yanwen Chen, Gregory S Cooper, Nancy Furey, Beth Bednarchik, Bronia M Alashkar, John Dumot, Ashley L Faulx, Stephen P Fink, Adam M Kresak, Basel Abusneineh, Jill Barnholtz-Sloan, Patrick Leahy, Martina L Veigl, Amitabh Chak, Sanford D Markowitz
BACKGROUND: Vitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett's esophagus (BE). We hypothesized that vitamin D supplementation may have beneficial effects on gene expression including 15-PGDH in BE. METHODS: BE subjects with low grade or no dysplasia received vitamin D3 (cholecalciferol) 50,000 international units weekly plus a proton pump inhibitor for 12 weeks...
2017: PloS One
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
#3
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/28881340/additional-benefits-of-routine-drugs-on-gastrointestinal-cancer-statins-metformin-and-proton-pump-inhibitors
#4
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
BACKGROUND: Commonly used medications including statins, metformin, and proton pump inhibitors (PPIs) effectively reduce the risk of esophageal, gastric, and colorectal cancer (CRC). SUMMARY: A number of observational studies and meta-analyses have shown that long-term statin use significantly reduces the incidence of gastrointestinal (GI) cancer. Moreover, statin use after GI cancer diagnosis has been significantly associated with better prognosis in large-scale cohort studies...
September 8, 2017: Digestive Diseases
https://www.readbyqxmd.com/read/28866702/a-fatal-gastric-perforation-secondary-to-ulcerated-metastasis-in-undiagnosed-breast-cancer-pathological-aspects-and-review-of-literature
#5
R Barranco, G F Orcioni, F Ventura
The authors describe a fatal case of gastric perforation secondary to an ulcerated metastasis in a woman with undiagnosed breast cancer. The 48-year-old woman, with no significant medical history, presented with weight loss, persistent dyspepsia and pain in the epigastric and mesogastric region. She was treated by her primary care physician with proton-pump inhibitors and antispasmodics. The following day she was found dead at her home. External examination showed a tumefaction in the lateral region of her left breast, near the axilla...
August 2017: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28861639/repositioning-of-proton-pump-inhibitors-in-cancer-therapy
#6
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/28844821/low-dose-rate-prostate-brachytherapy-4-8%C3%A2-week-postimplant-prostate-specific-antigen-a-novel-predictor-of-biochemical-failure-free-survival
#7
Cameron M Callaghan, Lin Wang, Abhishek Alluri, Andrew Lauve, Cynthia Boyer, William Russell
PURPOSE: The purpose of this study was to determine the relationship between patient, disease, and treatment variables and biochemical failure-free survival (bFFS) following low-dose-rate prostate brachytherapy (LDR-BT). METHODS AND MATERIALS: Data from 624 consecutive patients who received LDR-BT for localized prostate cancer between 2002 and 2012 at a single institution were collected for various patient, disease, and treatment characteristics including a 4-8 week postimplant PSA (4-8wkPSA)...
August 24, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28828196/use-of-proton-pump-inhibitors-in-general-practice
#8
Cesare Tosetti, Ilaria Nanni
AIM: To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency. METHODS: Thirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis...
August 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
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
#9
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/28752076/molecular-machineries-of-ph-dysregulation-in-tumor-microenvironment-potential-targets-for-cancer-therapy
#10
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/28750272/medication-use-and-kidney-cancer-risk-a%C3%A2-population-based-study
#11
Madhur Nayan, David N Juurlink, Peter C Austin, Erin M Macdonald, Antonio Finelli, Girish S Kulkarni, Robert J Hamilton
BACKGROUND: Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. METHODS: We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#12
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28705331/a-non-interventional-retrospective-cohort-study-of-the-interaction-between-methotrexate-and-proton-pump-inhibitors-or-aspirin
#13
E Boerrigter, M Crul
INTRODUCTION: Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent. No previous studies into the effect of low dose aspirin on the elimination of MTX in high-dose therapy have been performed...
July 10, 2017: Annales Pharmaceutiques Françaises
https://www.readbyqxmd.com/read/28704010/-smarter-medicine-in-ambulatory-care-beliefs-and-practices-of-family-doctors-and-training-of-future-clinicians
#14
Christine Cohidon, Kevin Selby, Jacques Cornuz, Jean-Michel Gaspoz, Nicolas Senn
Following an American and then international initiative, the Swiss Society of Internal Medicine launched the « Smarter Medicine » campaign in 2014 with five recommendations of activities to be avoided, focusing on low back pain, antibiotic prescriptions, pre-operative chest x-rays, prostate cancer screening and treatment with proton pump inhibitors. In 2016, 69 % of family physicians reported that they knew the recommendations and levels of agreement were very high. However, physicians reported differences between recommendations in how often they are followed in practice, and there remains room for improvement...
January 25, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28700346/restoring-microenvironmental-redox-and-ph-homeostasis-inhibits-neoplastic-cell-growth-and-migration-therapeutic-efficacy-of-esomeprazole-plus-sulfasalazine-on-3-mca-induced-sarcoma
#15
Enrica Balza, Patrizia Castellani, Paola Sanchez Moreno, Patrizia Piccioli, Iria Medraño-Fernandez, Claudia Semino, Anna Rubartelli
Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28682046/upper-gastrointestinal-conditions-nonmalignant-conditions-of-the-esophagus
#16
David S Estores, Ku-Lang Chang
Eosinophilic esophagitis (EE) is an allergic disorder of the esophagus. This diagnosis requires the presence of specific symptoms and a significantly elevated number of eosinophils in the esophageal lining as determined by endoscopic biopsies. Symptoms tend to be nonspecific among patients younger than 15 years. Among adults, dysphagia is the most common symptom. Comanagement with a gastroenterology subspecialist is essential, particularly for EE patients with a stricture. EE is commonly misdiagnosed as gastroesophageal reflux disease (GERD)...
July 2017: FP Essentials
https://www.readbyqxmd.com/read/28680717/effect-of-a-proton-pump-inhibitor-on-tumor-bleeding-prevention-in-unresectable-gastric-cancer-patients-a-double-blind-randomized-placebo-controlled-trial
#17
Young-Il Kim, Mi-Jung Kim, Sook Ryun Park, Hark Kyun Kim, Soo-Jeong Cho, Jong Yeul Lee, Chan Gyoo Kim, Gwang Ha Kim, Moo In Park, Byung-Ho Nam, Young Iee Park, Il Ju Choi
PURPOSE: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. MATERIALS AND METHODS: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS)...
June 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/28645482/proton-pump-inhibitors-and-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma
#18
Aly-Khan A Lalani, Rana R McKay, Xun Lin, Ronit Simantov, Marina D Kaymakcalan, Toni K Choueiri
INTRODUCTION: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and can affect the optimal absorption of concomitant oral medications, such as vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). The purpose of this study was to investigate the effect of PPI use on survival in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era. MATERIALS AND METHODS: We conducted a pooled analysis of mRCC patients treated in phase II and III clinical trials...
May 31, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28636554/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#19
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...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631728/acg-and-cag-clinical-guideline-management-of-dyspepsia
#20
REVIEW
Paul M Moayyedi, Brian E Lacy, Christopher N Andrews, Robert A Enns, Colin W Howden, Nimish Vakil
We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age...
July 2017: American Journal of Gastroenterology
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