Establishment of a PDTT Xenograft Model of Gastric Carcinoma and its Application in Personalized Therapeutic Regimen Selection
Establishment of a PDTT Xenograft Model of Gastric Carcinoma and its Application in Personalized Therapeutic Regimen Selection
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DOI：
10.5754/hge11136
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发表时间：
2011-09-01
影响因子：
--
通讯作者：
Teng, Lisong
中科院分区：
文献类型：
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作者：
Jin, Ketao;He, Kuifeng;Teng, Lisong
背景/目的：缺乏可靠预测抗癌药物反应的适当肿瘤模型仍然是个性化癌症治疗临床实践的主要缺陷。我们研究的目的是建立胃癌患者来源的肿瘤组织（PDTT）异种移植模型，用于个性化癌症治疗方案的选择和新型分子靶向药物的测试。方法：使用原发性胃癌的患者来源的肿瘤组织来创建异种移植模型。 11周后，收获异种移植物用于连续移植。采用H&E染色、免疫组织化学染色和蛋白质印迹法来确定异种移植物在连续移植过程中与原始肿瘤组织相比的生物稳定性。评价异种移植瘤对贝伐单抗（Avastin）、FP3和西妥昔单抗的药物敏感性。结果：异种移植模型成功建立。胃癌PDTT异种移植模型的早期传代显示在组织学、免疫组织化学以及蛋白质表达方面与原始临床肿瘤样本高度相似。 PDTT移植模型对所有受试药物均有效，其中贝伐珠单抗联合西妥昔单抗治疗组以及FP3联合西妥昔单抗治疗组的有效率较高。结论：建立了胃癌PDTT异种移植模型。它为个性化癌症治疗方案选择和新型分子靶向药物的测试提供了合适的模型。
Background/Aims: Lack of appropriate tumor models that reliably predict response to anticancer agents remains a major deficiency in the clinical practice of personalized cancer therapy. The aim of our study was to establish a patient-derived tumor tissue (PDTT) xenograft model of gastric carcinoma for personalized cancer therapeutic regimen selection and testing of novel molecularly targeted agents.Methodology: Patient-derived tumor tissue of primary gastric carcinoma was used to create the xenograft model. After 11 weeks, xenografts were harvested for serial transplantation. H&E staining, immunohistochemical staining and Western blotting were used to determine biological stability of the xenograft during serial transplantation compared with the original tumor tissue. Drug sensitivities of the xenograft to bevacizumab (Avastin), FP3 and cetuximab were evaluated.Results: Xenograft model was successfully established. Early passages of the PDTT xenograft model of gastric carcinoma revealed a high degree of similarity with the original clinical tumor sample regarding histology, immunohistochemistry, as well as protein expression. The PDTT xenograft model responded to all drugs tested, and a higher response rate was observed in bevacizumab in combination with cetuximab-treated group as well as FP3 in combination with cetuximab-treated group.Conclusions: A PDTT xenograft model of gastric carcinoma has been established. It provides an appropriate model for personalized cancer therapeutic regimen selection and testing of novel molecularly targeted agents.