Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

Yagi, Kenta; Mitstui, Marin; Zamami, Yoshito; Niimura, Takahiro; Izawa‐Ishizawa, Yuki; Goda, Mitsuhiro; Chuma, Masayuki; Fukunaga, Kimiko; Shibata, Takahiro; Ishida, Shunichi; Sakurada, Takumi; Okada, Naoto; Hamano, Hirofumi; Horinouchi, Yuya; Ikeda, Yasumasa; Yanagawa, Hiroaki; Ishizawa, Keisuke

doi:10.1002/cam4.3587

Cited by 14 publications

(14 citation statements)

References 33 publications

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“…This is because NSAID-induced gastric damage is known to include acid-dependent lesions, and because omeprazole inhibits gastric acid secretion through suppression of H+/K+ ATPase in the parietal cells [ 51 ]. Moreover, a previous study also showed an omeprazole-like proton pump inhibitor (PPI) [ 52 ] induced the VEGFA expression [ 53 ]. Similar findings regarding MDA, GSH, SOD, and CAT levels were also found in previous rat studies [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

Shaik

Eid

2022

Life

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One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFҡB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

Shaik

Eid

2022

Life

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“…The effect of vonoprazan on VEGF expression was evaluated using the same colorectal cancer cell line as in a previous study (Yagi et al, 2021). The results showed that vonoprazan does not upregulate VEGF expression at the gene and protein levels, whereas PPI does.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells

Ando-Matsuoka

Yagi

Takaoka

et al. 2022

Drug Development Research

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Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcriptionpolymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.

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“…The second approach was used for bevacizumab-induced hypertension ( Yagi et al, 2021 ). Hypertension is a frequent adverse event in bevacizumab-treated patients, and the development of hypertension has been suggested to be a biomarker of treatment response; FAERS found that hypertension was less frequently reported in bevacizumab-treated patients who were using omeprazole.…”

Section: Example Of Actual Research: Approach To Drug-induced Adverse Eventmentioning

confidence: 99%

Drug-Repositioning Approaches Based on Medical and Life Science Databases

et al. 2021

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Drug repositioning is a drug discovery strategy in which an existing drug is utilized as a therapeutic agent for a different disease. As information regarding the safety, pharmacokinetics, and formulation of existing drugs is already available, the cost and time required for drug development is reduced. Conventional drug repositioning has been dominated by a method involving the search for candidate drugs that act on the target molecules of an organism in a diseased state through basic research. However, recently, information hosted on medical information and life science databases have been used in translational research to bridge the gap between basic research in drug repositioning and clinical application. Here, we review an example of drug repositioning wherein candidate drugs were found and their mechanisms of action against a novel therapeutic target were identified via a basic research method that combines the findings retrieved from various medical and life science databases.

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Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

Cited by 14 publications

References 33 publications

Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells

Drug-Repositioning Approaches Based on Medical and Life Science Databases

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