Adverse Effects of Gefitinib on Skin and Colon in a Lung Cancer Mouse Model.

IF 2.5 4区 医学 Q3 ONCOLOGY Recent patents on anti-cancer drug discovery Pub Date : 2024-01-01 DOI:10.2174/1574892818666230727143750
Yalei Wang, Shuo Cheng, Huawei Zhang, Yali Zhang, Chengcheng Ding, Tiantian Peng, Weihang Chen, Ke Yang, Jiani Zhang, Yan Tan, Xu Wang, Zhaoheng Liu, Peng Wei, Miao Jiang, Qian Hua
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Abstract

Background: Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer.

Objective: The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice.

Methods: Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days.

Results: Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment.

Conclusion: The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study.

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吉非替尼对肺癌小鼠模型皮肤和结肠的不良影响
背景:吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI),在用于治疗非小细胞肺癌时经常会产生副作用:本实验旨在研究吉非替尼对小鼠皮肤和结肠的副作用:方法:以4-5周龄雄性Balb/c nu-nu裸鼠为异种移植瘤模型,在异种移植瘤长出9天后开始使用吉非替尼,剂量分别为150 mg/kg和225 mg/kg。同时跟踪小鼠的体重和肿瘤体积,并在治疗过程中观察小鼠皮肤不良反应和腹泻情况。14天后对动物组织进行生化和病理评估:结果:吉非替尼能有效减少裸鼠移植肿瘤的体积和重量,同时降低体重,提高肝脏和脾脏的指标。吉非替尼会引起小鼠皮肤不良反应和腹泻。进一步的病理学研究发现,吉非替尼治疗后,小鼠皮肤和结肠中与紧密连接相关的标记物减少,巨噬细胞和中性粒细胞增加:结论:研究结果表明,吉非替尼对皮肤和结肠有负面影响。本研究成功地模拟了吉非替尼诱导的小鼠皮肤和结肠不良反应。
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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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