title: Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.
abstract: 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.
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Ketao
authors.initials: K
authors.lastname: Jin
authors.forename: Guangliang
authors.initials: G
authors.lastname: Li
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Huanrong
authors.initials: H
authors.lastname: Lan
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.forename: Bojian
authors.initials: B
authors.lastname: Xie
authors.forename: Feilin
authors.initials: F
authors.lastname: Cao
authors.forename: Kuifeng
authors.initials: K
authors.lastname: He
authors.forename: Haohao
authors.initials: H
authors.lastname: Wang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
authors.forename: Tieming
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000556:secondary*; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A