研究者詳細 - 座間味　義人

論文 - 座間味　義人

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奥田浩人, 黒田智, 濱野裕章, 座間味義人

岡山医学会雑誌 136 ( 1 ) 29 - 32 2024年4月

抗がん剤心毒性の統合的な理解～基礎から臨床まで～大規模医療情報データベースを用いた薬剤性心毒性の予防法の開発

濱野裕章, 座間味義人, 牛尾聡一郎, 新村貴博, 合田光寛, 石澤有紀, 石澤啓介

薬学雑誌 144 ( 3 ) 257 - 264 2024年3月

A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases. 査読国際誌

Tatsuaki Takeda, Shiho Sugimoto, Jun Matsumoto, Naohiro Iwata, Akihiko Nakamoto, Aya Fukuma Ozaki, Hirofumi Hamano, Noritaka Ariyoshi, Yoshito Zamami

International journal of clinical pharmacy 46 ( 2 ) 536 - 541 2024年1月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear. AIM: We analysed two real-world databases, the World Health Organization's VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib. METHOD: Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis. RESULTS: Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group. CONCLUSION: This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer.

DOI： 10.1007/s11096-023-01687-6

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レセプトデータを用いたダサチニブと胃酸分泌抑制薬の薬物相互作用に関する検討

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

日本臨床薬理学会学術総会抄録集 44回 2 - I3 2024年1月

ステロイドはバンコマイシン関連腎障害を予防するビッグデータ解析・基礎研究・臨床研究の統合による検討

中馬真幸, 合田光寛, 座間味義人, 濱野裕章, 武智研志, 石田俊介, 坂東貴司, 新村貴博, 近藤正輝, 石澤有紀, 田崎嘉一, 石澤啓介

日本臨床薬理学会学術総会抄録集 44回 2 - 2 2024年1月

レセプトデータを用いたダサチニブと胃酸分泌抑制薬の薬物相互作用に関する検討

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

日本臨床薬理学会学術総会抄録集 44回 2 - I3 2024年1月

ステロイドはバンコマイシン関連腎障害を予防するビッグデータ解析・基礎研究・臨床研究の統合による検討

中馬真幸, 合田光寛, 座間味義人, 濱野裕章, 武智研志, 石田俊介, 坂東貴司, 新村貴博, 近藤正輝, 石澤有紀, 田崎嘉一, 石澤啓介

日本臨床薬理学会学術総会抄録集 44回 2 - 2 2024年1月

Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface. 査読国際誌

Tetta Takahashi, Nahoko Tomonobu, Rie Kinoshita, Ken-Ichi Yamamoto, Hitoshi Murata, Ni Luh Gede Yoni Komalasari, Youyi Chen, Fan Jiang, Yuma Gohara, Toshiki Ochi, I Made Winarsa Ruma, I Wayan Sumardika, Jin Zhou, Tomoko Honjo, Yoshihiko Sakaguchi, Akira Yamauchi, Futoshi Kuribayashi, Eisaku Kondo, Yusuke Inoue, Junichiro Futami, Shinichi Toyooka, Yoshito Zamami, Masakiyo Sakaguchi

Frontiers in oncology 14 1371342 - 1371342 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain. METHODS: Cell invasion was assessed using a transwell-based assay, protein-protein interactions by an immunoprecipitation-Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography. RESULTS: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion. CONCLUSION: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion.

DOI： 10.3389/fonc.2024.1371342

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The Association between PDE5 Inhibitors and Aneurysm/Arterial Dissection:A Pharmacovigilance Study Using WHO Safety Database. 査読

Koji Miyata, Yuki Izawa-Ishizawa, Takahiro Niimura, Hirofumi Hamano, Fuka Aizawa, Kenta Yagi, Kei Kawada, Yoshito Zamami, Mitsuhiro Goda, Keisuke Ishizawa

The journal of medical investigation : JMI 71 ( 1.2 ) 134 - 140 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Aneurysm and arterial dissection have been reported as adverse drug events, associated with angiogenesis inhibitors and fluoroquinolones. Specifically, several cases of severe arterial disease following cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors usage have recently been reported. It is necessary to ascertain the risks of serious adverse events caused by PDE5 inhibitors. We aimed to evaluate the association of aneurysm and artery dissection with PDE5 inhibitors using VigiBase, which is a World Health Organization database of spontaneously reported adverse events, for explorative hypothesis-generating analysis. We performed disproportionality analysis using a dataset from inception in 1967 to December 2022 and calculated reporting odds ratios (ROR) between PDE5 inhibitors and arterial diseases. We extracted 195,839 reports on PDE5 inhibitors with 254 reports of arterial disease as adverse events from VigiBase. Disproportionality analysis showed disproportional signals for PDE5 inhibitors (ROR, 2.30;95% confidence intervals, 2.04-2.61);disproportional signals were detected in analyses restricting the lesion site to the aorta or cerebral arteries. From stratified analysis, disproportional signals were noted in females, as well as males, generally recognized as a risk factor for artery diseases. This real-world data analysis suggests that PDE5 inhibitors may play a role in the development of lethal arterial disease. J. Med. Invest. 71 : 134-140, February, 2024.

DOI： 10.2152/jmi.71.134

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[Development of Preventive Methods for Drug-induced Cardiotoxicity Using a Large-scale Medical Information Database]. 査読

Hirofumi Hamano, Yoshito Zamami, Soichiro Ushio, Takahiro Niimura, Mitsuhiro Goda, Yuki Izawa-Ishizawa, Keisuke Ishizawa

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 144 ( 3 ) 257 - 264 2024年

記述言語：日本語掲載種別：研究論文（学術雑誌）

Cancer therapies have evolved considerably thereby substantially improving the survival of patients with cancer. However, cardiotoxicity, such as myocarditis and heart failure, induced by anticancer drugs, including immune checkpoint inhibitor(ICI)s and doxorubicin, present serious challenges. Numerous observations have indicated increased risks of cardiotoxicity- and cancer-related mortality in patients with drug-induced cardiotoxicity. Therefore, the prevention and management of drug-induced cardiotoxicity should be prioritized to enable sustainable long-term treatment while preserving patients' quality of life. Recently, medical research has been primarily focused on elucidation of therapeutic benefits and adverse events using medical big data, including worldwide databases of adverse events. The aim of the present study was to establish prevention strategies for drug-induced cardiotoxicity and advance data analytics. A data-driven approach was adopted to comprehensively analyze patient data and drug-induced cardiotoxicity. These data analytics revealed numerous risk factors, leading to the development of drugs that mitigate these factors. Furthermore, many unknown adverse events with molecularly targeted drugs were brought to light. Consequently, the importance of managing adverse events, guided by insights from data science, is predicted to increase. In this symposium review, we introduce our research exemplifying pharmaceutical studies utilizing medical big data. In particular, we discuss in detail the risk factors associated with myocarditis induced by immune checkpoint inhibitors along with prophylactic agents to mitigate doxorubicin-induced cardiotoxicity.

DOI： 10.1248/yakushi.23-00164-2

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Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan.

Yasuhisa Tatebe, Yohei Manabe, Yuta Tanaka, Takahiro Shiwaku, Motoharu Ochi, Kosuke Tamefusa, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Hirofumi Hamano, Kiminaka Murakawa, Yoshito Zamami

Biological & pharmaceutical bulletin 47 ( 9 ) 1575 - 1582 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

DOI： 10.1248/bpb.b24-00217

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Cardiovascular toxicity risk assessment of tyrosine kinase inhibitors: a pharmacovigilance study using the VigiBase database. 国際誌

Yusuke Igawa, Hirofumi Hamano, Satoru Esumi, Tatsuaki Takeda, Makoto Kajizono, Ryo Kikuoka, Ikuya Kimura, Yoshito Zamami

Frontiers in pharmacology 15 1472008 - 1472008 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Advances in the early detection and treatment of cancer have significantly improved the prognosis of patients with cancer. Tyrosine kinase inhibitors (TKIs) are effective targeted treatments for various malignancies that act by inhibiting kinase activity. Although these drugs share a common mechanism of action, they differ in their targeted kinases, pharmacokinetics, and side effects. TKIs can cause cardiovascular side effects, which adversely affect the prognosis of cancer survivors. This study aimed to assess the risk of cardiac toxicity associated with TKIs using the World Health Organization Global Database, VigiBase. METHODS: We conducted a cross-sectional analysis of data from VigiBase, a comprehensive global database of suspected drug reactions. The dataset included reports up to December 2022. We identified patients treated with Food and Drug Administration-approved TKIs and analyzed their age and sex data. The primary outcome was cardiovascular impairment, defined by 21 preferred terms in the Medical Dictionary for Regulatory Activities Terminology version 25.1. Disproportionality analysis using the reported odds ratio was performed to detect adverse cardiovascular signals. Statistical analyses were conducted using R 3.3.2, with a P-value <0.05 considered significant. RESULTS: Of the 32, 520, 983 reports in VigiBase, 23, 181, 539 were eligible for the analysis. Significant cardiovascular signals were identified for 17 TKIs, including erlotinib, gefitinib, and imatinib. Stratified analyses revealed potential sex- and age-related differences in the risk of adverse events. Heatmaps indicated significant signals for drugs such as lapatinib in males and gefitinib in younger patients. DISCUSSION: Our findings indicate that some TKIs, particularly those classified as VEGFR, BCR-ABL, and BTK, pose similar risks of cardiotoxicity, while others, including EGFR, HER2, and ALK TKIs, exhibit varied risk profiles. These results underscore the importance of individualized risk assessment and management of TKI-treated patients. In conclusion, this study provides valuable insights into the cardiotoxic risk of TKIs, which is essential for developing tailored treatment plans.

DOI： 10.3389/fphar.2024.1472008

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International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries. 査読国際誌

Toshihiro Koyama, Shunya Iinuma, Michio Yamamoto, Takahiro Niimura, Yuka Osaki, Sayoko Nishimura, Ko Harada, Yoshito Zamami, Hideharu Hagiya

Drug safety 47 ( 3 ) 237 - 249 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND OBJECTIVE: Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level. METHODS: This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates. RESULTS: The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92-3.18) in 2001 to 6.86 (95% confidence interval 5.76-7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20-50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019. CONCLUSIONS: The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally.

DOI： 10.1007/s40264-023-01387-0

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Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases. 査読

Takashi Bando, Masayuki Chuma, Hirofumi Hamano, Takahiro Niimura, Naoto Okada, Masateru Kondo, Yuki Izumi, Shunsuke Ishida, Toshihiko Yoshioka, Mizuho Asada, Yoshito Zamami, Kenshi Takechi, Mitsuhiro Goda, Koji Miyata, Kenta Yagi, Yuki Izawa-Ishizaka, Momoyo Azuma, Hiroaki Yanagawa, Yoshikazu Tasaki, Keisuke Ishizawa

Acta medica Okayama 77 ( 6 ) 595 - 605 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN.

DOI： 10.18926/AMO/66151

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ためになる薬の話薬物相互作用(58-タクロリムスの薬物相互作用)

木村郁哉, 濱野裕章, 鍛治園誠, 座間味義人

岡山医学会雑誌 135 ( 3 ) 167 - 171 2023年12月

ためになる薬の話薬物相互作用(58-タクロリムスの薬物相互作用)

木村郁哉, 濱野裕章, 鍛治園誠, 座間味義人

岡山医学会雑誌 135 ( 3 ) 167 - 171 2023年12月

Influence of vasopressin receptor antagonists on triple-whammy acute kidney injury: A VigiBase analysis. 査読国際誌

Satoru Mitsuboshi, Kenji Hayakawa, Hirofumi Hamano, Ayako Oshima, Tatsuaki Takeda, Kiminaka Murakawa, Hideki Mori, Yoshito Zamami

British journal of clinical pharmacology 90 ( 3 ) 900 - 904 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy AKI. The aim of this study was to evaluate whether vasopressin receptor antagonists affect triple-whammy AKI. This cross-sectional study used disproportionality analysis of VigiBase data to assess the risk of AKI with various diuretics. Although multiple logistic regression analysis showed that aldosterone antagonists (odds ratio [OR] 2.19, 95% CI 2.01-2.37), loop diuretics (OR 4.40, 95% CI 4.07-4.76) and thiazide diuretics (OR 1.98, 95% CI 1.83-2.15) increased the risk of AKI in patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system inhibitors (RASi), vasopressin receptor antagonists did not increase the risk of AKI in those patients. Vasopressin receptor antagonists might not influence the development of triple-whammy AKI.

DOI： 10.1111/bcp.15974

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Effect of pre-treatment of EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database. 査読国際誌

Naoto Okada, Hirofumi Hamano, Kenta Yagi, Takahiro Niimura, Fuka Aizawa, Mitsuhiro Goda, Yoshito Zamami, Takashi Kitahara, Keisuke Ishizawa

International journal of clinical pharmacology and therapeutics 62 ( 2 ) 69 - 76 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are key drugs for the treatment of EGFR mutation-positive lung cancer. While previous studies reported that the concomitant use of these drugs increases the risk of interstitial lung disease (ILD), the impact of sequential treatment on ILD risk is unknown. This study aimed to analyze the impact of EGFR-TKI pre-treatment on the risk of developing ILD after subsequent ICI administration. MATERIALS AND METHODS: We conducted a retrospective study using a Japanese health insurance claims database. ILD-naive lung cancer patients who had first ICI administration during the screening period from July 2014 to February 2019 were selected. Patients who had ILD within 1 year of receiving the first ICI dose were included in the ILD group. Multivariate logistic regression analysis was conducted to evaluate the effect of pre-treatment with EGFR-TKI on the development of ICI-associated ILD. RESULTS: A total of 353 patients were included, of which 61 were included in the ILD group. The median time to onset of ILD after ICI administration was 3 months. Multivariate logistic regression analysis revealed that pre-treatment with EGFR-TKI was not associated with ICI-associated ILD (odds ratio: 0.26, 95% confidence interval: 0.033 - 2.01). CONCLUSION: Although further analyses are required to confirm our findings, this study indicated that pre-treatment with EGFR-TKI might not increase the ILD risk after ICI treatment.

DOI： 10.5414/CP204491

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Reply to: Comments on Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics. 査読国際誌

Satoru Mitsuboshi, Hirofumi Hamano, Yoshito Zamami

International journal of cancer 154 ( 3 ) 586 - 587 2023年10月

Angiogenesis inhibitor-specific hypertension increases the risk of developing aortic dissection. 査読国際誌

Kaito Tsujinaka, Yuki Izawa-Ishizawa, Koji Miyata, Toshihiko Yoshioka, Kohei Oomine, Honoka Nishi, Masateru Kondo, Syuto Itokazu, Tatsumi Miyata, Takahiro Niimura, Maki Sato, Fuka Aizawa, Kenta Yagi, Masayuki Chuma, Yoshito Zamami, Mitsuhiro Goda, Keisuke Ishizawa

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 167 115504 - 115504 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aortic dissection is an adverse event of angiogenesis inhibitors; however, the association between the drugs and aortic dissection is unclear. Therefore, we investigated if and how angiogenesis inhibitors increase the onset of aortic dissection using pharmacologically-induced aortic dissection-prone model (LAB) mice, cultured endothelial cells, and real-world databases, which is a novel integrated research approach. Disproportionality analysis was performed and calculated using the reporting odds ratio as a risk signal using a worldwide database of spontaneous adverse events to estimate the risk of adverse events. Angiogenesis inhibitors, but not other hypertension-inducing drugs, showed significant risk signals for aortic aneurysms and dissection. A retrospective cohort analysis using JMDC, a medical receipt database in Japan, showed that the history of atherosclerosis and dyslipidemia, but not hypertension, were significantly associated with the onset of aortic dissection during angiogenesis inhibitor medication administration. For in vivo studies, sunitinib (100 mg/kg/day) was administered to LAB mice. Sunitinib increased systolic blood pressure (182 mmHg vs. 288 mmHg with sunitinib; p＜0.01) and the incidence of aortic dissection (40% vs. 59% with sunitinib; p = 0.34) in mice. In vivo and in vitro studies revealed that sunitinib increased endothelin-1 expression and induced endothelial cell damage evaluated by intracellular- and vascular cell adhesion molecule-1 expressions. The increased risk of developing aortic dissection with angiogenesis inhibitors is associated with the development of drug-specific hypertension via endothelial cell damage and endothelin-1 expression. Our findings are invaluable in establishing safer anticancer therapies and strategies to prevent the development of vascular toxicity in high-risk patients.

DOI： 10.1016/j.biopha.2023.115504

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