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Proton pump inhibitors and cancer

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https://www.readbyqxmd.com/read/28429247/a-review-of-the-novel-application-and-potential-adverse-effects-of-proton-pump-inhibitors
#1
REVIEW
Li-Yuan Yu, Lu-Ning Sun, Xue-Hui Zhang, Yue-Qi Li, Lei Yu, Zi-Qing-Yun Yuan, Ling Meng, Hong-Wen Zhang, Yong-Qing Wang
Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H(+)/K(+)-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on...
April 20, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28424965/assessment-of-drug-drug-interaction-potential-between-ceritinib-and-proton-pump-inhibitors-in-healthy-subjects-and-in-patients-with-alk-positive-non-small-cell-lung-cancer
#2
Yvonne Y Lau, Wen Gu, Tiffany Lin, Kalyanee Viraswami-Appanna, Can Cai, Jeffrey W Scott, Michael Shi
PURPOSE: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. METHODS: A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28420003/retrospective-analysis-of-the-risk-factors-for-grade-iv-neutropenia-in-oesophageal-cancer-patients-treated-with-a-docetaxel-cisplatin-and-5-fluorouracil-regimen
#3
Masahito Naito, Tomoya Yamamoto, Chikao Shimamoto, Yoshihiro Miwa
BACKGROUND: Previous Japanese trials of the docetaxel, cisplatin, and 5-fluorouracil regimen for oesophageal cancer have demonstrated that a large proportion of patients also develop grade IV neutropenia. Our aim was to examine the risk factors for neutropenia in patients treated with this regimen. METHODS: We retrospectively analysed the risk factors for developing grade IV neutropenia in 66 patients with oesophageal cancer using a multivariate analysis. RESULTS: After administering the docetaxel, cisplatin, and 5-fluorouracil regimen, 49 patients (74...
April 19, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28388576/proton-pump-inhibitor-ilaprazole-suppresses-cancer-growth-by-targeting-t-cell-originated-protein-kinase
#4
Mengzhu Zheng, Shanshan Luan, Suyu Gao, Li Cheng, Bin Hao, Jiacheng Li, Yao Chen, Xuemei Hou, Lixia Chen, Hua Li
T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28378028/up-regulation-of-autophagy-is-a-mechanism-of-resistance-to-chemotherapy-and-can-be-inhibited-by-pantoprazole-to-increase-drug-sensitivity
#5
Qian Tan, A M Joshua, M Wang, R G Bristow, B G Wouters, C J Allen, Ian F Tannock
BACKGROUND: Autophagy is a survival mechanism that allows recycling of cellular breakdown products, particularly in stressed cells. Here we evaluate the hypotheses that up-regulation of autophagy is a common mechanism of resistance to chemotherapy, and that drug resistance can be reversed by inhibiting autophagy with a proton pump inhibitor. METHODS: We exposed human PC3, LNCaP and MCF7 cells to seven clinically-used chemotherapy drugs ± pantoprazole, examined the up-regulation of autophagy and the effect on cellular proliferation by Western Blots, MTS assay and colony-forming assay...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28377310/risk-factors-for-extended-spectrum-beta-lactamase-producing-escherichia-coli-urinary-tract-infection-in-the-community-in-denmark-a-case-control-study
#6
Mette Søgaard, Uffe Heide-Jørgensen, Jan P Vandenbroucke, Henrik C Schønheyder, Christina Mje Vandenbroucke-Grauls
OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, as risk factors for ESBL E.coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with previous studies. METHODS: Population-based case-control study including 339 cases with community-onset ESBL E...
April 1, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28371597/role-of-proton-pumps-in-tumorigenesis
#7
REVIEW
V A Kobliakov
One of the differences between normal and cancer cells is lower pH of the extracellular space in tumors. Low pH in the extracellular space activates proteases and stimulates tumor invasion and metastasis. Tumor cells display higher level of the HIF1α transcription factor that promotes cell switch from mitochondrial respiration to glycolysis. The terminal product of glycolysis is lactate. Lactate formation from pyruvate is catalyzed by the specific HIF1α-dependent isoform of lactate dehydrogenase A. Because lactate accumulation is deleterious for the cell, it is actively exported by monocarboxylate transporters...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28364288/co-administration-of-proton-pump-inhibitors-ameliorates-nephrotoxicity-in-patients-receiving-chemotherapy-with-cisplatin-and-fluorouracil-a-retrospective-cohort-study
#8
Kenji Ikemura, Kosuke Oshima, Tomoyuki Enokiya, Akiharu Okamoto, Hiroyasu Oda, Toshiro Mizuno, Hajime Ishinaga, Yuichi Muraki, Takuya Iwamoto, Kazuhiko Takeuchi, Naoyuki Katayama, Masahiro Okuda
PURPOSE: The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity. METHODS: We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer...
March 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28350791/acid-suppressing-therapies-and-subsite-specific-risk-of-stomach-cancer
#9
E Christina M Wennerström, Jacob Simonsen, M Constanza Camargo, Charles S Rabkin
BACKGROUND: Associations of stomach cancer risk with histamine type-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) are controversial. We hypothesised that proximal extension of Helicobacter pylori infection from acid suppression would disproportionately increase cancers at proximal subsites. METHODS: A total of 1 563 860 individuals in the Danish Prescription Drug Registry first prescribed acid-suppressive drugs 1995-2011 were matched to unexposed population-based controls...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28323552/helicobacter-pylori-eradication-in-the-swedish-population
#10
Eva Doorakkers, Jesper Lagergren, Vijaya Krishna Gajulapuri, Steven Callens, Lars Engstrand, Nele Brusselaers
OBJECTIVES: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade. MATERIALS AND METHODS: This population-based study used data from the Swedish Prescribed Drug Register...
June 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28273868/pharmacological-potential-and-synthetic-approaches-of-imidazo-4-5-b-pyridine-and-imidazo-4-5-c-pyridine-derivatives
#11
REVIEW
Malwina Krause, Henryk Foks, Katarzyna Gobis
The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABAA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc...
March 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28259289/proton-pump-inhibitors-in-cancer-patients-how-useful-they-are-a-review-of-the-most-common-indications-for-their-use
#12
REVIEW
Gianmauro Numico, Vittorio Fusco, Pierfrancesco Franco, Fausto Roila
Proton-Pump Inhibitors (PPIs) are commonly prescribed in the general population and in cancer patients. A supposed role in the prevention of gastric mucosal damage apparently justify their use in patients undergoing cytotoxic chemotherapy, steroids and radiotherapy on the gastro-duodenal region. They are frequently given also to patients admitted to Intensive Care Units, for the prevention of stress-related gastric ulcers. The evidence about these use of gastroprotection is reviewed. In the majority of the cases the prescription of PPIs is not justified...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28254863/bone-pain-induced-by-multiple-myeloma-is-reduced-by-targeting-v-atpase-and-asic3
#13
Masahiro Hiasa, Tatsuo Okui, Yohance M Allette, Matthew S Ripsch, Ge-Hong Sun-Wada, Hiroki Wakabayashi, G David Roodman, Fletcher A White, Toshiyuki Yoneda
Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP(+)) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28206729/gut-microbiota-and-gastric-disease
#14
Dolores Sgambato, Agnese Miranda, Lorenzo Romano, Marco Romano
The gut microbiota may be considered a crucial "organ" of human body because of its role in the maintenance of the balance between health as well as disease. It is mainly located in the small bowel and colon, while, the stomach was long thought to be sterile in particular for its high acid production. In particular, stomach was considered "an hostile place" for bacterial growth until the identification of Helicobacter pylori (HP). Now, the stomach and its microbiota can be considered as two different "organs" that share the same place and they have an impact on each other...
February 15, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28155020/risks-factors-and-outcomes-of-clostridium-difficile-infection-in-patients-with-cancer-a-matched-case-control-study
#15
Andrew I T Hebbard, Monica A Slavin, Caroline Reed, Jason A Trubiano, Benjamin W Teh, Gabrielle M Haeusler, Karin A Thursky, Leon J Worth
PURPOSE: Clostridium difficile infection (CDI) is the leading cause of diarrhoea in hospitalised patients. Cancer populations are at high-risk for infection, but comprehensive evaluation in the current era of cancer care has not been performed. The objective of this study was to describe characteristics, risk factors, and outcomes of CDI in cancer patients. METHODS: Fifty consecutive patients with CDI at a large Australian cancer centre (2013-2015) were identified from the hospital pathology database...
February 2, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28118373/the-role-of-adjuvant-acid-suppression-on-the-outcomes-of-bleeding-esophageal-varices-after-endoscopic-variceal-ligation
#16
Cheng-Kun Wu, Chih-Ming Liang, Chien-Ning Hsu, Tsung-Hsing Hung, Lan-Ting Yuan, Seng-Howe Nguang, Jiunn-Wei Wang, Kuo-Lun Tseng, Ming-Kun Ku, Shih-Cheng Yang, Wei-Chen Tai, Chih-Wei Shih, Pin-I Hsu, Deng-Chyang Wu, Seng-Kee Chuah
The impact of adjuvant acid suppression via proton pump inhibitors or histamine-2 receptor antagonists after endoscopic variceal ligation remains uncertain. We therefore aimed to evaluate the effect of adjuvant acid suppression on the rebleeding and mortality rates in patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices. Data from 1997 to 2011 were extracted from the National Health Insurance Research Database in Taiwan. A total of 1576 cirrhotic patients aged > 18 years with a primary diagnosis of acute esophageal variceal bleeding who received endoscopic variceal ligation therapy were screened...
2017: PloS One
https://www.readbyqxmd.com/read/28089100/community-onset-clostridium-difficile-infection-at-a-tertiary-medical-center-in-southern-taiwan-2007-2015
#17
Chin-Shiang Tsai, Yuan-Pin Hung, Jen-Chieh Lee, Nan-Yao Lee, Po-Lin Chen, Ling-Shan Syue, Ming-Chi Li, Chia-Wen Li, Wen-Chien Ko
BACKGROUND: Clostridium difficile infection (CDI) is well-known as the major cause of infectious diarrhea in hospitalized patients. Community-onset CDI (CO-CDI) is an emerging threat. However, clinical information of CO-CDI in Taiwan remains scarce. METHODS: A retrospective study was conducted at a medical center in southern Taiwan. Symptomatic patients between 2007 and 2015 with C. difficile toxin or tcdB detected in stool were identified as CDI, and were classified as CO-CDI [including community-associated CDI (CA-CDI) and community-onset health care facility-associated CDI (CO-HCFA-CDI)] and health care facility-onset CDI (HCFO-CDI)...
December 18, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28088584/proton-pump-inhibition-and-cancer-therapeutics-a-specific-tumor-targeting-or-it-is-a-phenomenon-secondary-to-a-systemic-buffering
#18
REVIEW
Enrico Spugnini, Stefano Fais
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28077309/physical-and-biological-characteristics-of-multi-drug-resistance-mdr-an-integral-approach-considering-ph-and-drug-resistance-in-cancer
#19
REVIEW
Ziad Omran, Paula Scaife, Simon Stewart, Cyril Rauch
The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance...
January 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28072858/proton-pump-inhibitors-do-not-reduce-the-risk-of-esophageal-adenocarcinoma-in-patients-with-barrett-s-esophagus-a-systematic-review-and-meta-analysis
#20
Qiang Hu, Tian-Tian Sun, Jie Hong, Jing-Yuan Fang, Hua Xiong, Stephen J Meltzer
OBJECTIVES: Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE. METHODS: A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library...
2017: PloS One
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