动物造模,药效评价,鳞状细胞癌 z-bio 2024-06-19 392

　　【 Modeling Mechanism 】 Numerous genes are involved in the pathogenesis of SCC, and gene modified animal models with high or no expression of specific genes can spontaneously or externally induce SCC.

　　There are many related models, and the following are only examples to illustrate. For example, selective inhibition of Rel/NF-KB and overexpression of IKB - α in mouse skin can cause scales and hair development disorders on the scalp, back, and tail at birth, and spontaneous generation of SCC at 8 weeks. Transgenic mice with high expression of the neu oncogene were found to have significantly thickened epidermis and extremely uncoordinated hair growth at 3 days of birth. Histological examination showed severe hair follicle and intraepithelial hyperplasia, severe epidermal hyperplasia, abnormal keratinization in the dermis and subcutaneous tissue, and SCC like changes in many parts of the epidermis. For example, transgenic mice overexpressing wild-type human c-serine in the basal layer using bovine keratin 5 as a promoter began to spontaneously develop SCC at 3 months, with an incidence rate of approximately 70% after 1 year.

　　Papillomavirus infection is one of the causes of SCC. Under the stimulation of carcinogenic factors, almost 100% of transgenic mice expressing the E6 oncogene of multi breast mouse papillomavirus develop SCC.

　　Transgenic mice with high expression of cyclin dependent kinase 4 exhibit high sensitivity to carcinogenic effects of chemical stimuli. Under the induction of chemical stimuli, the probability of developing SCC in the transgenic mouse significantly increased, and the number of poorly developed and atypical in situ cancerous skin lesions histologically increased. In addition, transgenic mice expressing integrin subunit α 2 β 1 and the gene XPA -/- related to dry skin pigmentation above the basal layer of the epidermis showed a significant increase in the probability of developing SCC after receiving carcinogenic stimulation.

　　【 Model Evaluation and Application 】 SCC is a disease with multiple triggers and long-term accumulation of damage. Genetically modified animals can explore the mechanism of gene action in tumor occurrence as much as possible, and provide a platform for finding corresponding therapeutic drugs and taking preventive measures against tumor occurrence.