胃癌患者源性肿瘤异种移植动物模型的精确化疗。

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-08-01 Epub Date: 2025-02-19 DOI:10.1007/s00210-025-03903-8
Yiyin Zhang, Yongming Yang, Jiayi Zhou, Qianqian Yu, Lixia Chen, Lili Zhao, Yongsheng Meng, Jing Wang, Lei Yan, Ziyang Huang, Shuchen Song, Wenqi Bai, Ruifang Sun, Xihua Yang
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引用次数: 0

摘要

本研究旨在建立胃癌患者源性肿瘤异种移植(PDX)模型,并将其应用于化疗药物的药效学研究。从而为胃癌患者的个性化治疗提供指导。取手术患者新鲜胃癌组织,移植至NOG小鼠体内建立PDX模型。采用免疫荧光和免疫组织化学方法鉴定人源标记物。外显子测序用于验证PDX模型中人源化特征的保留。采用PDX模型评价6种化疗药物(奥沙利铂、顺铂、紫杉醇、氟尿嘧啶、替加富、卡培他滨)的疗效及卡培他滨的最佳剂量。本研究成功建立了胃癌PDX模型,移植成功率分别为P0 ~ P1(45%)、P1 ~ P2(88.89%)、P2 ~ P3(87.5%)。重要的是,原始的肿瘤特征有效地保存到P3。药物筛选结果显示卡培他滨对胃癌PDX模型有明显的抗肿瘤作用。本研究成功建立了胃癌PDX模型,突出了其在化疗药物筛选和个性化治疗方面的潜力。移植成功率和原始肿瘤特征的保存强调了该模型的可靠性和对未来研究的相关性。药物筛选的发现,特别是卡培他滨的有效性,为胃癌患者的精确治疗策略提供了一条有希望的途径。
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Patient-derived tumor xenograft animal model of gastric cancer in precision chemotherapy.

This study aims to establish a patient-derived tumor xenograft (PDX) model for gastric cancer and apply it in pharmacodynamic studies for chemotherapeutic agents. So as to provide guidance for personalized treatment in gastric cancer patients. Fresh gastric cancer tissues were collected from surgical patients and transplanted into NOG mice to establish PDX model. Human source markers were identified by immunofluorescence and immunohistochemistry methods. Exon sequencing was used to verify the retention of humanized features in the PDX model. The efficacy of six chemotherapeutic drugs (oxaliplatin, cisplatin, paclitaxel, fluorouracil, Tegafur, capecitabine) and optimal dose of capecitabine were evaluated by the PDX model. The study has successfully established the PDX model of gastric cancer with transplantation success rates of P0 to P1 (45%), P1 to P2 (88.89%), and P2 to P3 (87.5%). Importantly, original tumor features were effectively preserved till P3. Drug screening results revealed notable antitumor effect of capecitabine in the PDX model of gastric cancer. The study has successfully established a gastric cancer PDX model, highlighting its potential for chemotherapy drug screening and personalized treatment. The transplantation success rates and preservation of original tumor features underscore the model's reliability and relevance for future studies. Findings from drug screening, especially capecitabine's effectiveness, suggest a promising avenue for precision treatment strategies in gastric cancer patients.

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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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