Faculty Profiles - ZAMAMI Yoshito

Papers - ZAMAMI Yoshito

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副作用対策は今後も進歩するのか?マンネリ化させない研究のデザイン力医療ビッグデータ解析と基礎研究を融合した研究手法による抗がん剤誘発副作用に対する予防法の探索

合田光寛, 神田将哉, 吉岡俊彦, 新村貴博, 櫻田巧, 小川敦, 岡田直人, 相澤風花, 八木健太, 濱野裕章, 石澤有紀, 座間味義人, 石澤啓介

日本臨床腫瘍薬学会雑誌 25 241 - 241 2022.5

合田光寛, 神田将哉, 吉岡俊彦, 新村貴博, 櫻田巧, 小川敦, 岡田直人, 相澤風花, 八木健太, 濱野裕章, 石澤有紀, 座間味義人, 石澤啓介

日本臨床腫瘍薬学会雑誌 25 241 - 241 2022.5

フェンタニルクエン酸塩経皮吸収型製剤0.5mgの使用実態と安全性の評価

鍛治園誠, 佐藤晶子, 高下典子, 太田佳男, 片山英樹, 座間味義人

日本臨床腫瘍薬学会雑誌 25 186 - 186 2022.5

Discovery of preventive drugs for cisplatin-induced acute kidney injury using big data analysis. International journal

Masaya Kanda, Mitsuhiro Goda, Akiko Maegawa, Toshihiko Yoshioka, Ami Yoshida, Koji Miyata, Fuka Aizawa, Takahiro Niimura, Hirofumi Hamano, Naoto Okada, Takumi Sakurada, Masayuki Chuma, Kenta Yagi, Yuki Izawa-Ishizawa, Hiroaki Yanagawa, Yoshito Zamami, Keisuke Ishizawa

Clinical and translational science 15 ( 7 ) 1664 - 1675 2022.4

Language：English Publishing type：Research paper (scientific journal)

Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.

DOI： 10.1111/cts.13282

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A web-based survey of educational opportunities of medical professionals based on changes in conference design during the COVID-19 pandemic. International journal

Kenta Yagi, Yasutaka Sato, Satoshi Sakaguchi, Mitsuhiro Goda, Hirofumi Hamano, Fuka Aizawa, Mayuko Shimizu, Arisa Inoue-Hamano, Toshihide Nishimori, Masato Tagi, Marina Kanno, Rie Matsuoka-Ando, Toshihiko Yoshioka, Yoshiko Matstubara, Yuki Izawa-Ishizawa, Rieko Shimizu, Akinori Maruo, Yurika Kuniki, Yoshika Sakamoto, Sayuri Itobayashi, Yoshito Zamami, Hiroaki Yanagawa, Keisuke Ishizawa

Education and information technologies 27 ( 7 ) 1 - 16 2022.4

Language：English Publishing type：Research paper (scientific journal)

Owing to the coronavirus disease 2019 (COVID-19) pandemic, understanding how to hold future online academic conferences effectively is imperative. We assessed the impact of COVID-19 on academic conferences, including facilities and settings for attendance, participation status, cost burden, and preferences for future styles of holding conferences, through a web-based questionnaire survey of 2,739 Japanese medical professionals, from December 2020 to February 2021. Of the participants, 28% preferred web conferences, 60% preferred a mix of web and on-site conferences, and 12% preferred on-site conferences. Additionally, 27% of the presenters stopped presenting new findings at web conferences. The proportion of participants who audio-recorded or filmed the sessions, despite prohibition, was six times higher at web than face-to-face conferences. Since the COVID-19 outbreak, the percentage of participants attending general presentations decreased from 91 to 51%. While web conferencing offers advantages, these are offset by a decrease in presentations pertaining to novel findings and data. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-022-11032-5.

DOI： 10.1007/s10639-022-11032-5

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Drug interaction (53. Interaction of traditional Japanese herbal medicines in chemotherapy)

Naohiro Iwata, Satoru Esumi, Yoshito Zamami

Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 134 ( 1 ) 43 - 47 2022.4

Identification of prophylactic drugs for oxaliplatin-induced peripheral neuropathy using big data. International journal

Yoshito Zamami, Takahiro Niimura, Takehiro Kawashiri, Mitsuhiro Goda, Yutaro Naito, Keijo Fukushima, Soichiro Ushio, Fuka Aizawa, Hirofumi Hamano, Naoto Okada, Kenta Yagi, Koji Miyata, Kenshi Takechi, Masayuki Chuma, Toshihiro Koyama, Daisuke Kobayashi, Takao Shimazoe, Hiromichi Fujino, Yuki Izawa-Ishizawa, Keisuke Ishizawa

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 148 112744 - 112744 2022.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Drug repositioning is a cost-effective method to identify novel disease indications for approved drugs; it requires a shorter developmental period than conventional drug discovery methods. We aimed to identify prophylactic drugs for oxaliplatin-induced peripheral neuropathy by drug repositioning using data from large-scale medical information and life science information databases. METHODS: Herein, we analyzed the reported data between 2007 and 2017 retrieved from the FDA's database of spontaneous adverse event reports (FAERS) and the LINCS database provided by the National Institute of Health. The efficacy of the drug candidates for oxaliplatin-induced peripheral neuropathy obtained from the database analysis was examined using a rat model of peripheral neuropathy. Additionally, we compared the incidence of peripheral neuropathy in patients who received oxaliplatin at the Tokushima University Hospital, Japan. The effects of statins on the animal model were examined in six-week-old male Sprague-Dawley rats and seven or eight-week-old male BALB/C mice. Retrospective medical chart review included clinical data from Tokushima University Hospital from April 2009 to March 2018. RESULTS: Simvastatin, indicated for dyslipidemia, significantly reduced the severity of peripheral neuropathy and oxaliplatin-induced hyperalgesia. In the nerve tissue of model rats, the mRNA expression of Gstm1 increased with statin administration. A retrospective medical chart review using clinical data revealed that the incidence of peripheral neuropathy decreased with statin use. CONCLUSION AND RELEVANCE: Thus, drug repositioning using data from large-scale basic and clinical databases enables the discovery of new indications for approved drugs with a high probability of success.

DOI： 10.1016/j.biopha.2022.112744

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Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study. International journal

Takumi Sakurada, Hiroshi Nokihara, Tadashi Koga, Yoshito Zamami, Mitsuhiro Goda, Kenta Yagi, Hirofumi Hamano, Fuka Aizawa, Hirokazu Ogino, Seidai Sato, Yasushi Kirino, Hisatsugu Goto, Yasuhiko Nishioka, Keisuke Ishizawa

The oncologist 27 ( 7 ) e554-e560 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Rash eruptions are a common side-effect of pemetrexed, for which the administration of 8 mg/day of dexamethasone for 3 days from the day preceding pemetrexed administration is recommended. This study aimed to prospectively assess the effectiveness of prophylactic administration of low-dose dexamethasone for pemetrexed-induced rashes. METHODS: This single-arm, phase II study recruited patients with non-squamous non-small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions. RESULTS: Twenty-five patients were enrolled between September 2017 and May 2019. The incidence of rash after 3 weeks was 16.7%. Rashes erupted mainly on the upper half of the body, such as the chest and neck, and were of grades 1 and 2 in 2 patients each. No rashes of grade 3 or higher were observed, and there were no adverse events associated with additional corticosteroids. CONCLUSION: Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666).

DOI： 10.1093/oncolo/oyab077

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Association between statin use and daptomycin-related musculoskeletal adverse events: A mixed approach combining a meta-analysis and a disproportionality analysis. International journal

Masayuki Chuma, Aki Nakamoto, Takashi Bando, Takahiro Niimura, Yutaka Kondo, Hirofumi Hamano, Naoto Okada, Mizuho Asada, Yoshito Zamami, Kenshi Takechi, Mitsuhiro Goda, Koji Miyata, Kenta Yagi, Toshihiko Yoshioka, Yuki Izawa-Ishizawa, Hiroaki Yanagawa, Yoshikazu Tasaki, Keisuke Ishizawa

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 75 ( 8 ) 1416 - 1422 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. METHODS: We used a mixed approach that combines two methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the FDA Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. RESULTS: In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.43-10.26) but not DAP-related myopathy (OR: 1.72, 95% CI: 0.95-3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69, 95% CI: 4.31-7.51) and rhabdomyolysis (ROR: 5.77, 95% CI: 4.33-7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. CONCLUSION: The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety.

DOI： 10.1093/cid/ciac128

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各種プロトンポンプ阻害剤のがん細胞におけるVEGF発現に与える影響

安藤里英, 八木健太, 岡本尚大, 高岡麻佑, 相澤風花, 濱野裕章, 石澤有紀, 合田光寛, 座間味義人, 石澤啓介

日本薬学会年会要旨集 142年会 28H - pm04S 2022.3

自発的副作用報告データベースを用いた、抗線維化薬と間質性肺疾患との関連性についての検討

大西明日香, 名和秀起, 濱野裕章, 新村貴博, 宮田晃志, 八木健太, 合田光寛, 座間味義人, 石澤啓介

日本薬学会年会要旨集 142年会 28PO1 - 46 2022.3

有害事象自発報告データベースに基づく光学異性体が薬剤間相互作用に与える影響についての検討

根石茉実, 濱野裕章, 新村貴博, 宮田晃志, 八木健太, 合田光寛, 座間味義人, 石澤啓介, 名和秀起

日本薬学会年会要旨集 142年会 28PO1 - 45S 2022.3

医療ビックデータを活用した免疫チェックポイント阻害剤関連肺炎のリスク因子に関する検討

朝田瑞穂, 見神尊修, 新村貴博, 座間味義人, 中馬真幸, 合田光寛, 石澤啓介, 植沢芳広

日本薬学会年会要旨集 142年会 26PO1 - 14 2022.3

医療ビックデータを活用した免疫チェックポイント阻害剤関連肺炎のリスク因子に関する検討

朝田瑞穂, 見神尊修, 新村貴博, 座間味義人, 中馬真幸, 合田光寛, 石澤啓介, 植沢芳広

日本薬学会年会要旨集 142年会 26PO1 - 14 2022.3

Atenolol and mortality events in patients with chronic kidney disease: Analysis of data from the Japanese Adverse Drug Event Report database. International journal

Satoru Mitsuboshi, Takahiro Niimura, Fuka Aizawa, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa

Basic & clinical pharmacology & toxicology 130 ( 4 ) 553 - 556 2022.2

The effect of Eucommia ulmoides leaf extract on aortic dissection onset in mice

Miyata Koji, Izawa-Ishizawa Yuki, Kondo Masateru, Tsujinaka Kaito, Omine Kohei, Nishi Honoka, Aizawa Fuka, Hamano Hirofumi, Yagi Kenta, Zamami Yoshito, Goda Mitsuhiro, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 1-SS-37 2022

Language：Japanese Publisher：Japanese Pharmacological Society

Aortic dissection is a severe aortic disease, in which the aortic wall is separated into two layers at the medial level, resulting in two lumens being created, a true and a false lumen. Most cases have a sudden onset resulting in death. Therefore, it is required to establish a preventive strategy. Eucommia ulmoides leaf (EUL) extract contains various flavonoids such as quercetin, chlorogenic acid, geniposidic acid, and so on, and it is suggested to have a protective effect against cardiovascular diseases. In this study, we investigated the preventive effect of EUL on the onset of aortic dissection.

We generated pharmacologically-induced aortic dissection model mice (LAB model). In C57Bl / 6J mice, three agents are administered; (1) nitric oxide synthase inhibitor (L-NAME) that causes vascular endothelial damage, (2) angiotensin II (Ang II) that causes hypertention, and (3) lysyl oxidase inhibitor (BAPN) that causes medial fragility. EUL extract was orally administered daily throughout the experiment.

Hypertension, caused by Ang II+BAPN loading was significantly suppressed by EUL. In the LAB model, macrophage infiltration into the aortic wall was increased, but it was suppressed by EUL administration. As a result, EUL showed the preventive effects against the onset of aortic aneurysm, dissection, and death from rupture.

DOI： 10.1254/jpssuppl.95.0_1-ss-37

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The Effect of Combined Bcr-Abl Inhibitor and ALDH Inhibitor on Chronic Myelogenous Leukemia

Yurika Kuniki, Yagi Kenta, Yoshida Rina, Okamoto Naoki, Ando Rie, Yamakawa Yusuke, Hamano Hirofumi, Niimura Takahiro, Aizawa Fuka, Izawa-Ishizawa Yuki, Goda Mitsuhiro, Zamami Yoshito, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 1-SS-66 2022

Language：Japanese Publisher：Japanese Pharmacological Society

【Introduction】Chronic myelogenous leukemia (CML) has become a disease with five-year-survival rate of more than 90% according to appearance of Bcr-Abl inhibitor. Stopping treatment with Bcr-Abl inhibitors leads to relapse in many patients. This is due to the fact that Bcr-Abl inhibitors are not effective against cancer stem cells, and suggests that a different drug is necessary to eradicate cancer stem cells. ALDH is overexpressed in cancer stem cells and promotes their survival. We have shown in past studies that Bcr-Abl inhibitors do not inhibit ALDH expression. In this study, we examine the effect of ALDH inhibitors on CML.

【Methods】We examined the effects of an ALDH inhibitor using K562 cells, which are CML cell line. We verified the effect of an ALDH inhibitor against CML using a WST-8 assay. We then measured ALDH protein expression using flow cytometry.

【Results】ALDH inhibitors reduced cell survival in a concentration-dependent manner, and when combined with a Bcr-Abl inhibitor, cell viability was synergistically decreased. ALDH protein expression was decreased in cells treated with ALDH inhibitor alone or Bcr-Abl inhibitor alone according to flow cytometry. In cells treated with ALDH inhibitor and Bcr-Abl inhibitor, ALDH protein expression was more strongly repressed.

【Conclusion】The results of this study suggest that ALDH inhibitor use might be effective in CML treatment.

DOI： 10.1254/jpssuppl.95.0_1-ss-66

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Development of Supportive Care for Anticancer Drugs Based on Real World Data; Evaluation of the Therapeutic and Preventive Effects of Statins on Peripheral Neuropathy

Aizawa Fuka, Kajimoto Haruna, Moriyama Daishi, Okabayashi Ami, Goda Mitsuhiro, Hamano Hirofumi, Yagi Kenta, Izawa- Ishizawa Yuki, Zamami Yoshito, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 1-O-024 2022

Language：Japanese Publisher：Japanese Pharmacological Society

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the adverse events associated with the anticancer drugs, however, almost available analgesic drugs lack efficacy against CIPN. Previously our results using medical database, FAERS, suggested that HMG-CoA reductase inhibitors (statins) have the potential to ameliorate oxaliplatin-induced peripheral neuropathy (OIPN). In this study, we elucidated the effect and mechanism of statins to OIPN model mice and PC12 cell. Three statins (simvastatin, atorvastatin, and rosuvastatin) could not show the therapeutic and preventive effects against oxaliplatin-induced cold allodynia. On the other hand, repeated orally administration of each statins ameliorate development of oxaliplatin-induced mechanical allodynia and significantly suppressed already established allodynia induced by oxaliplatin. A gene-related database revealed that the expression of glutathione S-transferase (GST) family members is regulated by statins. Decreased survival rate of PC12 cells by treatment of oxaliplatin was canceled cotreatment of each statin for 24 hours. Furthermore, cell protective effect of statin was disappeared transfection of gstmu1 siRNA into PC12 cells. These our results suggest that statins might be one of the novel supportive care, which have neuroprotective effect to OIPN.

DOI： 10.1254/jpssuppl.95.0_1-o-024

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Effects of sodium valproate on cisplatin-induced acute kidney injury

Yoshioka Toshihiko, Goda Mitsuhiro, Kanda Masaya, Yoshida Ami, Itobayashi Sayuri, Sugimoto Yugo, Izawa-Ishizawa Yuki, Yagi Kenta, Aizawa Fuka, Hamano Hirofumi, Okada Naoto, Zamami Yoshito, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 1-SS-48 2022

Language：Japanese Publisher：Japanese Pharmacological Society

OBJECTIVE: Cisplatin-induced acute kidney injury (AKI) is well known, and the nephrotoxicity of cisplatin restricts its clinical application. Currently, there are no drugs are recommended for the prevention of cisplatin-induced AKI. Forced hydration and diuresis may partially prevent nephrotoxicity of cisplatin, but it is still difficult to entirely prevent kidney injury. Thus, establishment of a new preventive method against cisplatin-induced AKI is required. Therefore, in this study, the purpose of this study was to clarify the efficacy of sodium valproate in cisplatin-induced AKI.

METHODS: In order to establish cisplatin‐induced AKI animal model, C57BL/6 mice were administered with either cisplatin (15 mg/kg, i.p.) or saline (control). The degree of renal damage was assessed by various renal function parameters and pathological evaluation. The effect of sodium valproate on cisplatin-induced cytotoxicity was evaluated using HK2 cells, MKN-1 cells and LLC cells.

RESULTS: Cisplatin treatment worsened various renal function parameters and tubular damage scores, which were significantly improved by co-treatment with sodium valproate. The decrease in cell viability of HK2 cells by cisplatin was significantly improved by co-treatment with sodium valproate. On the other hand, sodium valproate had no adverse effect on the reduction of cell viability of various cancer cells by cisplatin.

CONCLUSIONS: The results of this study indicated that sodium valproate could act as a potential preventive drug for cisplatin-induced AKI.

DOI： 10.1254/jpssuppl.95.0_1-ss-48

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Exploration of preventive drugs for sunitinib-induced heart failure utilizing large-scale medical database

Yoshika Sakamoto, Tomochika Nanami, Hamano Hirofumi, Goda Mitsuhiro, Niimura Takahiro, Aizawa Fuka, Yagi Kenta, Nakamura Akihito, Nishiuchi Shiori, Izawa-Ishizawa Yuki, Zamami Yoshito, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 1-SS-35 2022

Language：Japanese Publisher：Japanese Pharmacological Society

BACKGROUND: Several studies have reported that patients treated with sunitinib, a tyrosine kinase inhibitor, have developed left ventricular dysfunction and heart failure, but there is currently no treatment for heart failure with sunitinib. The purpose of the present study is to identify candidate drugs for the treatment of sunitinib-induced heart failure using a large medical database. METHOD: We analyzed the FDA Adverse Event Reporting System (FAERS) and the WHO global adverse event reporting database (VigiBase) to find candidate drugs for prevention of sunitinib-induced heart failure. The effects of the candidate drugs on cell viability and cell morphology were evaluated using the WST-8 assay and immunostaining in H9c2 cells derived from rat cardiac rhabdomeres. RESULTS: FAERS and VigiBase searches revealed significantly higher reporting odds ratio (ROR) of heart failure in patients treated with sunitinib than in those not treated with sunitinib. The ROR was reduced by concomitant use of Vitamin D (FAERS: ROR 0.50, 95% CI 0.26-0.96; VigiBase: ROR 0.37, 95% CI 0.10-0.95). In vitro, Vitamin D significantly improved the viability and maintained the cell morphology in H9c2 cells exposed to sunitinib. CONCLUSION: The findings suggest the potential value of Vitamin D in preventing sunitinib-induced heart failure.

DOI： 10.1254/jpssuppl.95.0_1-ss-35

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