Faculty Profiles - ZAMAMI Yoshito

Papers - ZAMAMI Yoshito

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Incidence of Myocarditis Caused by Drugs Used for Ulcerative Colitis as Examined Using VigiBase, a Spontaneous Adverse Drug Reaction Reporting Database

Yumi Kawai, Yasuko Kurata, Hirofumi Hamano, Takahiro Niimura, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa, Hideki Nawa

Biological and Pharmaceutical Bulletin 48 ( 4 ) 383 - 389 2025.4

Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy. International journal

Aya F Ozaki, Michael Sayer, Hirofumi Hamano, Misako Nagasaka, Benjamin J Lee, Jean Doh, Ali Naqvi, Nareh Nowrouzi, Yoshito Zamami, Pranav M Patel

Cardio-oncology (London, England) 11 ( 1 ) 26 - 26 2025.3

Language：English

INTRODUCTION: Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights. METHODS: We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them. RESULTS: In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04-1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02-1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39-1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79-2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37-1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases. DISCUSSION/CONCLUSION: Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival.

DOI： 10.1186/s40959-025-00300-1

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Evaluation of Interstitial Lung Disease Complications Caused by Biologic Agents Using a Spontaneous Adverse Drug Reaction Reporting Database International journal

Ayu Minagi, Hideki Nawa, Mitsuhiro Goda, Takahiro Niimura, Koji Miyata, Hirofumi Hamano, Yoshito Zamami, Keisuke Ishizawa

Pharmacology Research & Perspectives 13 ( 2 ) e70063 2025.2

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

ABSTRACT

Interstitial lung disease (ILD) is a clinically relevant adverse event associated with biologic agent use. However, the current incidence of ILD remains unclear as large‐scale risk assessments of biologic agents have not been conducted. The aim of this study was to clarify the association between biologic agent use and ILD development in clinical practice by detecting adverse event signals using a spontaneous adverse drug reaction database. The VigiBase database is used for spontaneous adverse event reporting. The analysis focused on nine biologics used to treat psoriasis, rheumatoid arthritis, and Crohn's disease. The safety of each biologic agent was evaluated using the information component signal detection method. There were 32,520,983 reports in VigiBase, of which 68,489 (0.21%) were for ILD. Signals were mainly detected for tumor necrosis factor‐α inhibitors when the information component for ILD caused by biologic agents was calculated. Comorbidity analysis in patients who developed ILD and analysis of the time from the start of treatment with each drug to ILD onset showed differences for each biologic agent. ILD is a serious adverse effect of biologic agents, and there are several cases in which a causal relationship with ILD development cannot be ruled out. The occurrence of interstitial ILD should be noted when using biologics, particularly TNF‐α inhibitors.

DOI： 10.1002/prp2.70063

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Photoinitiators Induce Histamine Production in Human Mast Cells.

Taro Miura, Yoichi Kawasaki, Hirofumi Hamano, Yoshito Zamami, Toshiaki Sendo

Acta medica Okayama 79 ( 1 ) 51 - 58 2025.2

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

Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro.

DOI： 10.18926/AMO/68362

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Authors' Reply to Noguchi et al. Comment on: "Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors Used in Patients with Diabetes and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database". International journal

Toshiaki Sakamoto, Hirotaka Miyamoto, Junya Hashizume, Hayato Akamatsu, Tomoaki Akagi, Yukinobu Kodama, Hirofumi Hamano, Yoshito Zamami, Kaname Ohyama

Clinical drug investigation 45 ( 1 ) 47 - 49 2024.12

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

BACKGROUND AND OBJECTIVES: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently become a standard treatment for heart failure and renal failure. The number of patients using these drugs is expected to increase further. However, no adverse drug event profiles have been published for the use of SGLT2i in patients without diabetes. To analyze and clarify the differences in adverse event profiles associated with the use of SGLT2i in patients with diabetes or heart failure using the Japanese Adverse Drug Event Report (JADER) database, a Japanese reporting system for adverse events. METHODS: The JADER database, containing reports submitted between April 2004 and January 2024, was used. Our study focused on patients with diabetes or heart failure, analyzing adverse events associated with empagliflozin and dapagliflozin. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated for signal detection. RESULTS: We identified risks of adverse drug events such as ketoacidosis, urinary tract infection, dehydration, and acidosis in both patient groups. However, the risks of cerebral infarction and ischemic heart disease were identified only in patients with diabetes, while risks of renal dysfunction, hypoglycemia, and sepsis were identified only in those with heart failure. CONCLUSION: Adverse events should be managed appropriately for patients using SGLT2i, as the adverse event profiles differ between those with diabetes and those with heart failure. Understanding these differences is crucial for improving patient safety and optimizing treatment outcomes.

DOI： 10.1007/s40261-024-01414-7

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International trends in biliary tract cancer-related mortality, 2000-2022: An observational study of the World Health Organization mortality database. International journal

Quynh Thi Vu, Yoshito Nishimura, Ko Harada, Hiroki Ito, Tsukasa Higashionna, Akinari Maruo, Keisaku Harada, Tatsuaki Takeda, Hirofumi Hamano, Yoshito Zamami, Hideharu Hagiya, Toshihiro Koyama

Hepatology (Baltimore, Md.) 2024.12

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

BACKGROUND AIMS: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. APPROACH RESULTS: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000-2022 based on available data from countries. Trends in age-standardised mortality rates (ASRs) during 2013-2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% confidence interval: 2.5-3.1) in 2000, and 2.7 (2.3-3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8-6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3-2.9) and 2.2 (1.8-2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to GBC decreased by 45.5%, and those due to eCCA remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013-2022, with iCCA-associated ASRs showing increasing trends in many countries. CONCLUSIONS: Although internationally estimated BTC-associated ASRs showed a stable trend over the last two decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.

DOI： 10.1097/HEP.0000000000001200

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ためになる薬の話薬物相互作用(がん悪液質治療薬の相互作用)

川上英治, 奥田浩人, 濱野裕章, 座間味義人

岡山医学会雑誌 136 ( 3 ) 135 - 138 2024.12

Evaluating the impact of loperamide on irinotecan-induced adverse events: a disproportionality analysis of data from the World Health Organization pharmacovigilance database (VigiBase) International journal

Tomoaki Akagi, Hirofumi Hamano, Hirotaka Miyamoto, Tatsuaki Takeda, Yoshito Zamami, Kaname Ohyama

European Journal of Clinical Pharmacology 81 ( 1 ) 129 - 137 2024.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

PURPOSE: SN-38, the active metabolite of irinotecan, may cause adverse events necessitating treatment discontinuation and management. Diarrhea, which is treated with loperamide, is one such event. However, loperamide may delay SN-38 elimination, causing more adverse events. Therefore, understanding the adverse events caused by symptomatic drugs is crucial for safe drug therapy. This study aimed to assess the association between loperamide and irinotecan-induced adverse events. METHODS: We analyzed data up to December 2022 from VigiBase, the World Health Organization's adverse event database. The study used reporting odds ratios (RORs) to evaluate the associations between concomitant medications and irinotecan-induced adverse events. Fisher's exact probability test was used to analyze the adverse events. Logistic regression analysis was performed to identify associated adverse event signals. RESULTS: Of the 32,520,983 cases analyzed, 57,454 involved the use of irinotecan. Among these, 1589 (2.8%) patients were co-treated with loperamide. Signals for neutropenia (ROR 1.37, 95% confidence interval (CI) 1.20-1.57, p < 0.001), anemia (ROR 1.81, 95% CI 1.43-2.30, p < 0.001), and alopecia (ROR 1.89, 95% CI 1.30-2.74, p < 0.01) were detected with concomitant loperamide. Multivariate logistic regression analysis confirmed that concomitant loperamide use was associated with signals for neutropenia, anemia, and alopecia. CONCLUSION: Our results suggest that loperamide increases the risk of irinotecan-induced adverse events and enhances irinotecan toxicity. The study methodology may be useful for predicting adverse event risk when choosing symptomatic therapy drugs during irinotecan use.

DOI： 10.1007/s00228-024-03767-6

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Other Link： https://link.springer.com/article/10.1007/s00228-024-03767-6/fulltext.html

Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors used in Patients with Diabetes Mellitus and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database. International journal

Toshiaki Sakamoto, Hirotaka Miyamoto, Junya Hashizume, Hayato Akamatsu, Tomoaki Akagi, Yukinobu Kodama, Hirofumi Hamano, Yoshito Zamami, Kaname Ohyama

Clinical drug investigation 44 ( 10 ) 761 - 771 2024.10

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

DOI： 10.1007/s40261-024-01394-8

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Assessing the effects of interprofessional education by hospital pharmacists on pharmaceutical students using a self-evaluation scale. International journal

Fuka Aizawa, Hirofumi Hamano, Naoto Okada, Kenta Yagi, Mitsuhiro Goda, Hideki Nawa, Yuya Horinouchi, Toshimi Nakamura, Harumasa Hakuno, Kazuaki Shinomiya, Yoshito Zamami, Masahiko Azuma, Masashi Akaike, Keisuke Ishizawa

Journal of pharmaceutical health care and sciences 10 ( 1 ) 61 - 61 2024.10

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

BACKGROUND: Understanding the roles and competencies of professions outside of one's specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals. METHODS: Sixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi's Scale of Social Skills (KiSS-18). RESULTS: Regardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6-3.8), p < 0.001; IPE: 3.7, 95% CI (2.5-4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5-6.1), p < 0.001; IPE: 6.7 95% CI (3.0-10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2-2.8), p = 0.025] post-practice than those without IPE awareness. CONCLUSIONS: This study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future. TRIAL REGISTRATION: This study was retrospectively registered and conducted in compliance with the "Ethical Guidelines for Medical Research Involving Human Subjects" and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544).

DOI： 10.1186/s40780-024-00382-6

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Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione-S-transferase. International journal

Fuka Aizawa, Haruna Kajimoto, Ami Okabayashi, Daishi Moriyama, Kenta Yagi, Shimon Takahashi, Yuhei Sonoda, Takahiro Shibata, Mitsuhiro Goda, Takahiro Niimura, Yuki Izawa-Ishizawa, Hirofumi Hamano, Kei Kawada, Yoshito Zamami, Keisuke Ishizawa

Neurochemistry international 180 105863 - 105863 2024.9

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

Some therapeutic agents have been found to have effects beyond their primary indications. Peripheral neuropathy, a common side effect of chemotherapy, remains inadequately treated. Identifying additional properties of existing medications could thus uncover novel therapeutic avenues. Previous studies have identified an additional effect of simvastatin in reducing neuropathy; however, the mechanism underlying this effect remains unclear. We investigated the novel effects of statins on chemotherapy-induced peripheral neuropathy in mice. Mice treated with oxaliplatin or paclitaxel did not show exacerbation or improvement in cold sensations upon acetone testing with statin administration. However, concurrent oral statin treatment mitigated the nociceptive response to mechanical stimuli induced by each anti-tumor agent. Co-administration of a glutathione-S-transferase inhibitor, which modulates redox reactions, abolished the ameliorative effect of statins on mechanical nociceptive behavior. Additionally, the glutathione-S-transferase inhibitor did not affect normal sensory perception or impair the anti-tumor effect of chemotherapy agents. A search for GST-associated molecules and pathways using artificial intelligence revealed that GST regulates inflammatory cytokines as a regulatory or causative gene. Our findings suggest that statins have class effects that ameliorate cytotoxic anti-cancer drug-induced mechanical allodynia via GST pathway activation.

DOI： 10.1016/j.neuint.2024.105863

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Unveiling the association between fluoroquinolones and aortic diseases using real-world database analysis and pharmacological experiments. Reviewed International journal

Koji Miyata, Yuki Izawa-Ishizawa, Kaito Tsujinaka, Honoka Nishi, Syuto Itokazu, Tatsumi Miyata, Masateru Kondo, Toshihiko Yoshioka, Takahiro Niimura, Fuka Aizawa, Kenta Yagi, Maki Sato, Mizusa Hyodo, Hirofumi Hamano, Kei Kawada, Masayuki Chuma, Yoshito Zamami, Koichi Tsuneyama, Mitsuhiro Goda, Keisuke Ishizawa

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 179 117418 - 117418 2024.9

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

Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation.

DOI： 10.1016/j.biopha.2024.117418

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Ameliorating effect of chotosan and its active component, Uncaria hook, on lipopolysaccharide-induced anxiety-like behavior in mice Reviewed International journal

Yasumasa Okawa, Soichiro Ushio, Yasuhisa Izushi, Yoshihisa Kitamura, Yoshito Zamami, Toshiaki Sendo

Frontiers in Pharmacology 15 1471602 - 1471602 2024.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Introduction

In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice.

Methods

To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light–dark test 24 h after LPS treatment.

Results

Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT_1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT_2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT)_2A receptor mRNA expression in the frontal cortex, whereas 5-HT_1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT_2A receptor.

Discussion

These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT_2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors.

DOI： 10.3389/fphar.2024.1471602

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ためになる薬の話薬物相互作用(60-慢性疼痛治療薬の薬物相互作用)

高橋徹多, 東恩納司, 濱野裕章, 座間味義人

岡山医学会雑誌 136 ( 2 ) 80 - 82 2024.8

mRNAワクチン

田中雄太, 座間味義人

岡山医学会雑誌 136 ( 2 ) 83 - 84 2024.8

ためになる薬の話薬物相互作用(60-慢性疼痛治療薬の薬物相互作用)

高橋徹多, 東恩納司, 濱野裕章, 座間味義人

岡山医学会雑誌 136 ( 2 ) 80 - 82 2024.8

A network-based trans-omics approach for predicting synergistic drug combinations. Reviewed International journal

Midori Iida, Yurika Kuniki, Kenta Yagi, Mitsuhiro Goda, Satoko Namba, Jun-Ichi Takeshita, Ryusuke Sawada, Michio Iwata, Yoshito Zamami, Keisuke Ishizawa, Yoshihiro Yamanishi

Communications medicine 4 ( 1 ) 154 - 154 2024.7

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

BACKGROUND: Combination therapy can offer greater efficacy on medical treatments. However, the discovery of synergistic drug combinations is challenging. We propose a novel computational method, SyndrumNET, to predict synergistic drug combinations by network propagation with trans-omics analyses. METHODS: The prediction is based on the topological relationship, network-based proximity, and transcriptional correlation between diseases and drugs. SyndrumNET was applied to analyzing six diseases including asthma, diabetes, hypertension, colorectal cancer, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). RESULTS: Here we show that SyndrumNET outperforms the previous methods in terms of high accuracy. We perform in vitro cell survival assays to validate our prediction for CML. Of the top 17 predicted drug pairs, 14 drug pairs successfully exhibits synergistic anticancer effects. Our mode-of-action analysis also reveals that the drug synergy of the top predicted combination of capsaicin and mitoxantrone is due to the complementary regulation of 12 pathways, including the Rap1 signaling pathway. CONCLUSIONS: The proposed method is expected to be useful for discovering synergistic drug combinations for various complex diseases.

DOI： 10.1038/s43856-024-00571-2

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レセプトデータを用いたダサチニブの有効性・安全性に胃酸分泌抑制薬が及ぼす影響の評価

亀沖真希, 牛尾聡一郎, 佐田光, 建部泰尚, 濱野裕章, 座間味義人

The Journal of Toxicological Sciences 49 ( Suppl. ) S128 - S129 2024.7

免疫チェックポイント阻害薬誘発心筋炎の発症予測モデルの構築

山元黎奈, 濱野裕章, 中込昂希, 座間味義人, 上原孝

The Journal of Toxicological Sciences 49 ( Suppl. ) S126 - S127 2024.7

COVID-19ワクチン接種後の小児の心筋炎リスクに関する大規模研究

東さくら, 濱野裕章, 座間味義人

The Journal of Toxicological Sciences 49 ( Suppl. ) S125 - S125 2024.7

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Papers - ZAMAMI Yoshito