Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.
Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.
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DOI：
10.1371/journal.pone.0028384
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhu T
中科院分区：
文献类型：
--
作者：
Jin K;Li G;Cui B;Zhang J;Lan H;Han N;Xie B;Cao F;He K;Wang H;Xu Z;Teng L;Zhu T
缺乏能够可靠地预测对抗癌剂的反应的原发性肿瘤和相应转移的适当肿瘤模型仍然是癌症治疗的临床实践中的主要缺陷。本研究的目的是建立结肠癌淋巴转移和肝转移的患者源性肿瘤组织（PDTT）异种移植模型，用于检测新型分子靶向药物。采用原发性结肠癌、淋巴结转移瘤和肝转移瘤的PDTT建立异种移植瘤模型。苏木精-伊红染色、免疫组化染色、全基因组基因表达分析、焦磷酸测序、qRT-PCR和蛋白质印迹法用于确定异种移植物在连续移植期间与原始肿瘤组织相比的生物学稳定性。原发性结肠癌、淋巴结转移和肝转移的PDTT异种移植模型的早期传代揭示了在组织学、免疫组织化学、基因表达和突变状态以及mRNA表达方面与原始临床肿瘤样品的高度相似性。在我们确定这些异种移植物模型保留了与原始肿瘤相似的组织病理学特征和分子特征后，评价了异种移植物对新型VEGF靶向剂FP 3的药物敏感性。本研究成功建立了结肠癌淋巴结转移和肝转移的PDTT异种移植瘤模型。它们为新型分子靶向药物的测试提供了合适的模型。
The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.
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影响因子：
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作者：
Jin, Ketao;He, Kuifeng;Teng, Lisong
通讯作者：
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影响因子：
11.5
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通讯作者：
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影响因子：
3.3
作者：
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