Browsing by Subject "Proton pump inhibitor"

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    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing
    (Wiley, 2021) Lima, John J.; Thomas, Cameron D.; Barbarino, Julia; Desta, Zeruesenay; Van Driest, Sara L.; El Rouby, Nihal; Johnson, Julie A.; Cavallari, Larisa H.; Shakhnovich, Valentina; Thacker, David L.; Scott, Stuart A.; Schwab, Matthias; Uppugunduri, Chakradhara Rao S.; Formea, Christine M.; Franciosi, James P.; Sangkuhl, Katrin; Gaedigk, Andrea; Klein, Teri E.; Gammal, Roseann S.; Furuta, Takahisa; Medicine, School of Medicine
    Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
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    Long-term follow-up results of endoscopic treatment of gastroesophageal reflux disease with the MUSE™ endoscopic stapling device
    (Springer, 2016-08) Kim, Hong Joo; Kwon, Chang-Il; Kessler, William R.; Selzer, Don J.; McNulty, Gail; Bapaye, Amol; Bonavina, Luigi; Lehman, Glen A.; Department of Medicine, IU School of Medicine
    BACKGROUND: The initial 6-month data for MUSE™ (Medigus, Omer, Israel) endoscopic stapling device were reported (Zacherl et al. in Surg Endosc 29:220-229, 2015). The current study aims to evaluate the long-term clinical outcome of 37 patients who received endoscopic gastroesophageal reflux disease (GERD) treatment with the MUSE™ device. METHODS: Efficacy and safety data for 37 patients were analyzed at baseline, 6 months, and 4 years post-procedure. In one center (IU), efficacy and safety data were evaluated at baseline, 6 months post-procedure, and then annually up to 4 years. RESULTS: No new complications have been reported in our long-term analysis. The proportions of patients who remained off daily PPI were 83.8 % (31/37) at 6 months and 69.4 % (25/36) at 4 years post-procedure. GERD-Health Related Quality of Life (HRQL) scores (off PPI) were significantly decreased from baseline to 6 months and 4 years post-procedure. The daily dosage of GERD medications, measured as omeprazole equivalents (mean ± SD, mg), decreased from 66.1 ± 33.2 at baseline to 10.8 ± 15.9 at 6 months and 12.8 ± 19.4 at 4 years post-procedure (P < 0.01). CONCLUSIONS: In our multi-center prospective study, the MUSE™ stapling device appears to be safe and effective in improving symptom scores as well as reducing PPI use in patients with GERD. These results appeared to be equal to or better than those of the other devices for endoluminal GERD therapy. Future studies with larger patient series, sham control group, and greater number of staples are awaited.
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    Proton pump inhibitors suppress DNA damage repair and sensitize treatment resistance in breast cancer by targeting fatty acid synthase
    (Elsevier, 2021) Wang, Chao J.; Li, Deren; Danielson, Jacob A.; Zhang, Evan H.; Dong, Zizheng; Miller, Kathy D.; Li, Lang; Zhang, Jian-Ting; Liu, Jing-Yuan; Pharmacology and Toxicology, School of Medicine
    Human fatty acid synthase (FASN) is the sole cytosolic enzyme responsible for de novo lipid synthesis. FASN is essential for cancer cell survival and contributes to drug and radiation resistance by up-regulating DNA damage repair but not required for most non-lipogenic tissues. Thus, FASN is an attractive target for drug discovery. However, despite decades of effort in targeting FASN, no FASN inhibitors have been approved due to poor pharmacokinetics or toxicities. Here, we show that the FDA-approved proton pump inhibitors (PPIs) effectively inhibit FASN and suppress breast cancer cell survival. PPI inhibition of FASN leads to suppression of non-homologous end joining repair of DNA damages by reducing FASN-mediated PARP1 expression, resulting in apoptosis from oxidative DNA damages and sensitization of cellular resistance to doxorubicin and ionizing radiation. Mining electronic medical records of 6754 breast cancer patients showed that PPI usage significantly increased overall survival and reduced disease recurrence of these patients. Hence, PPIs may be repurposed as anticancer drugs for breast cancer treatments by targeting FASN to overcome drug and radiation resistance.