Establishment Of The Human Bile Duct Carcinoma Model In Nude Mice And Its Application

The research on bile duct carcinoma becomes the focus of the surgeons' attentions because of its increase in morbidity, difficulty of diagnosis in the early stage, low resection rate and poor prognosis. In order to explore its biological characteristics, discover various methods for early diagnosis and treatment, it is necessary to establish a serial human bile duct carcinoma animal model, due to difference of pathological types, various degrees of differentiation and different biological characteristics. We established a well differentiated mucinous adenocarcinoma model and a moderately differentiated papillary adenocarcinoma model of human bile duct carcinoma in nude mice by transplanting human histologically intact tumor tissues. These models maintained the biological characteristics of their original tumor tissues, passed 13 passages and tissues of implanted tumors can be offered to international and national researchers. We used human moderately differentiated bile duct carcinoma nude mouse model to evaluate the effect of chemotherapeutic drugs and it was found that MMC, ADM, VCR, TAXOL, DDP exhibited therapeutic effect on nude mice bearing human bile duct carcinoma. Furthermore, we have made preliminary study on the mechanism of anti-tumor effect of TAXOL. Influencing cell proliferation and angiogenesis may be related to TAXOL inhibition effect to the human bile duct carcinoma in nude mice. There is no report on this field in national literatures. This study includes three parts.Part I Establishment of the Human Bile Duct Carcinoma Model in Nude MiceObjectives To establish the implanted tumor models of human bile duct carcinoma in nude mice.Methods Surgical specimens of patients with bile duct carcinoma were implanted into the subcutaneous layer and other locations of nude mice and implantationcontinued. Growth curves of implanted tumors were drawn, its morphological and biological characteristics were observed and tumor markers in serum of mice and tumor tissues were examined.Results A well differentiated mucinous adenocarcinoma model and a moderately differentiated papillary adenocarcinoma model of human bile duct carcinomas in nude mice were established and named as HBDCM1-ZSH and HBDCM2-ZSH respectively. Mice with implanted tumors of model No.l and model No.2 exhibited 98.1% and 100% implantability. Latent periods were 26d and 21d respectively and mean doubling times were 3.3d/mm3 and 2.75d/mm3. Implanted tumors exhibited the characteristics of original tumors in morphology. Chromosomal analysis revealed a range of numerical abnormalities 67 ?84 in HBDCM1-ZSH and 66 ?88 in HBDCM2-ZSH. HBDCM1-ZSH expressed CEA, CA19-9, CK7, CK19, CK20, PCNA, AB and PAS, while HBDCM2-ZSH expressed CEA, CA19-9, CK7, CK19, bcl-2, p53 and PCNA. CEA, CA19-9 in serum of mice were also increased. Two models have been passed 13 passages. After frozen storage, implanted tumor tissues were subcutaneously inoculated into mice and all grew well.Conclusions HBDCM1-ZSH and HBDCM2-ZSH are the human-like bile duct carcinomas and provide animal models for research on bile duct carcinoma.