止吐药对唑贝妥昔单抗诱发雪貂胃损伤和呕吐的影响

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Fumitaka Kinugasa , Satoru Kajikawa , Jane Weng , Tohru Ugawa , Hiroshi Fushiki , Yosuke Yamanaka , Masanori Nagata , Gillian Haggerty , Shinobu Akuzawa , Taisuke Nakazawa , Hiroshi Suzuki , Taiji Sawamoto
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引用次数: 0

摘要

Claudin-18剪接变体2(CLDN18.2)是一种紧密连接蛋白,是一种细胞类型特异性很强的抗原,在分化的胃粘膜细胞中表达。CLDN18.2在胃黏膜细胞中的表达可能会在恶性转化时保留下来,并显示在包括胃/胃食管交界腺癌在内的多种肿瘤表面。唑贝妥昔单抗是一种针对 CLDN18.2 的基因工程高纯度嵌合(小鼠/人 IgG1)抗体。唑贝妥昔单抗的不良反应包括恶心和呕吐。为了研究人类恶心和呕吐的机理,我们对服用唑贝妥昔单抗后的雪貂进行了呕吐(反胃和呕吐)评估和组织病理学评估。所有接受唑贝妥昔单抗治疗的雪貂在用药后一小时内都经常出现呕吐现象。组织病理学评估显示,胃黏膜表面是与呕吐相关的组织损伤的主要部位。研究人员还考察了止吐药(地塞米松、昂丹司琼、福沙吡坦和奥氮平)对唑贝妥昔单抗诱导的呕吐的影响。福沙匹坦显示出抑制呕吐的作用,使用地塞米松或与其他止吐药同时使用福沙匹坦往往会减轻胃组织损伤。接受唑贝妥昔单抗治疗的患者出现呕吐可能与胃黏膜损伤有关,止吐药可减轻胃肠道不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets

Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type–specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events.

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来源期刊
CiteScore
6.20
自引率
2.90%
发文量
104
审稿时长
31 days
期刊介绍: Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.
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