Animal Models of Liver Cancer: Current Status and Application in Preclinical Research

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC develops in various causes – Viral hepatitis infection, toxins, or other liver conditions - by activation of oncogenes and/or inactivation of tumor suppressors. Understanding of signal pathways and protein-protein interactions critical in tumor development may lead to novel treatment strategy. To evaluate the progression of HCC and effects of potential therapies, various animal models have been established. Experimental models of HCC provide valuable tools to investigate the risk factors, new treatment modalities and biologic characteristics. Subcutaneous xenograft models have been widely used in the past. However, with the advancement of in vivo imaging technology, investigators are more concerned with the orthotopic models nowadays. Genetically engineered mouse models have greatly facilitated studies of gene function in HCC development. Lately, a novel approach for stable gene expression in mouse hepatocytes by hydrodynamic injection has been developed. Each model has its own advantages and disadvantages. Therefore, selecting the optimal models based on study objectives is necessary. In this review, we highlight both the frequently used mouse models and some emerging ones with emphasis on their merits or defects, and give advices for investigators to choose a “best-fit” animal model in HCC research.

The Incidence Rate and Severity of Orthotopic Lung Cancer in an Animal Model Depends on the Number of A549 Cells and Transplantation Period / 한국실험동물학회지

The incidence rate of lung cancer is continually increasing, and lung cancer is the leading cause of cancer-related death worldwide. Nevertheless, few therapeutic methods are available for lung cancer. Therefore, establishing appropriate lung cancer animal models is important to investigate mechanisms and to evaluate new drugs for lung cancer. In the present study, we transplanted non-small cell lung cancer A549 human adenocarcinoma cells (2x10(4), 2.0x10(5), and 2.0x10(6) cells) into the right lobe of BALB/c nude mice via the intercostal space to develop an orthotopic lung cancer animal model that is minimally invasive and similar to human lung cancer. We then investigated the incidence rate and severity of lung cancer according to the A549 cell number (2x10(4), 2.0x10(5), and 2.0x10(6) cells) and transplantation periods (4~23 days). Lung cancer development was confirmed with gross examination, which was supported by histopathological examination. These results indicate that the incidence rate and severity of lung cancer was increased depending on the number of transplanted cells and transplantation period which the cell number and duration are increasing risk of lung cancer. Thus, this study can provide appropriate reference data to develop an orthotopic lung cancer animal model using the non-small cell lung cancer A549 cell line for researching mechanisms and evaluating candidate drugs, including various approaches for treating lung cancer.

Induction of Anti-tumor Immunity by Vaccination with E7 of HPV16 and IL-12 / 대한산부인과학회잡지

OBJECTIVE: Interleukin-12 is well known to induce cellular immune response materials and suppress the tumor growth. HPV infection has significant roles in cervical carcinogenesis, and HPV oncoprotein E6 and E7 are important roles in formation and maintenance of cervical cancer. E7 specific immune response was detected in cervical cancer patients, and this shows that E7 protein would be important in potential immunetherapy in cervical cancer. This study is aimed to investigate antitumor effect and E7 immune response by injection of adenovirus IL-12 and E7 in cervical cancer animal model. METHODS: In the cervical cancer animal model using C57BL/6 mice and HPV16 E7 immortalized hosts, 5 X 10(8) pfu/100 ul of PBS, AdLacZ, AdE7 and AdIL-12 were injected into the tumor mass when the tumor sized is increased to 7-8 mm. After the injection, the tumor size was caliperated every 2-3 days, and pathologic and blood studies were done on day 1, 3, 5, 7, 11, 12, and 21 days. The expression level of IL-12 and INF- and E7 specific immune response were measured by ELISA. RESULTS: After the injection of AdIL-12 into the tumor mass, 45% of tumor growth suppression was noted in comparison with control group. In the cases of combination injections of AdIL-12 and AdE7, 80% growth suppression was observed, and complete regression was shown in 40% of the study group. After injection of AdIL-12, the expression of IL-12 in the tumor mass was 9 time higher than that of control group, and 6 times higher in blood sample in comparison with control group. In the group with combined AdIL-12 and AdE7, the highest expression of INF- was noted in comparison with single injection of AdIL-12 or control group. IgGI and IgG2b isotype expression level increased 2.5 times and 2.2 times respectively 3 weeks after adenovirus injection. CONCLUSION: In cervical cancer animal model, IL-12 and E7 application using Adenovirus vector is significant antitumor effect and this demonstrates the potential immunotherapy in near future.

Influence of doxorubicin chemotherapy on the expression of epithelial growth factor in the Balb/c mouse hepatocarcinoma / 中国癌症杂志

Purpose:To investigate the influence of doxorubicin chemotherapy on overexpression of epithelial growth factor. Methods:Cancer animal model was made and treated with doxorubicin. The concentration of EGF protein in Plasma and mRNA in cancer tissue were detected by ELISA and Real-time quantitative RT-PCR respectively and the correlation of this parameter was evaluated. Results:The plasma concentrations of EGF expression were 3X Group 1.19?0.42 pg/ml, 1X Group 1.61?0.51 pg/ml, control group 2.13?0.68 pg/ml, and normal 0.91?0.33 pg/ml respectively. The concentration of EGF were analysed by ANOVA q test. The median concentrations of mRNA were 3X Group 1.6?10 3 copies/ml, 1X Group 8.5?10 4 copies/ml, control 4?10 5 copies/ml, and normal 2.5?10 2 copies/ml respectively, and were analysed by rank-sum test. It was shown that the control group had higher EGF and EGFR expression level than those treated with doxorubicin. EGF and EGFR expression of 3X Group were lower than that of 1X Group but remained higher than that of normal (P