动物造模,药效评价,膀胱癌 z-bio 2024-07-08 310

　　[Modeling mechanism] Gene modified bladder cancer animal models can be divided into microinjection method, retroviral infection method and embryonic stem cell method according to the way of gene introduction, of which microinjection method is more mature. Microinjection of purified target gene fragments into fertilized eggs, random integration of target genes into mouse chromosomes, and distribution in each individual cell with embryonic differentiation.

　　【 Modeling Method 】

　　1. Research on transgenic methods has found that a 3.6kb long sequence upstream of the mouse Uroplakin II gene can guide the specific expression of oncogenes in the urethra. The sequence was fused with its inducible oncoprotein gene SV40T to construct a UP II-SV40T chimeric gene, which was transfected into mice to produce transitional epithelial carcinoma with highly similar phenotype and transformation pattern to humans. Using the Uroplakin II gene to promote high expression of epidermal growth factor in the urinary tract transitional epithelium, it was found that transgenic mice with high levels of epidermal growth factor receptor mRNA exhibited significant transitional epithelial proliferation and high expression of proliferating cell nucleus antigen. Furthermore, it was found that the combination of epidermal growth factor and SV40T in transgenic mice can promote the development of SV40T induced in situ epithelial carcinoma into highly malignant bladder tumors. It can be inferred that epidermal growth factor has a synergistic carcinogenic effect on SV 40T.

　　2. Gene transfection studies have found that transfection of oncogenes such as H-ras can lead to bladder transitional epithelial carcinoma; Individuals with high expression of calcium binding protein S100A4 have a higher incidence of bladder tumors and a tendency towards metastasis; In the MY-3L tumor in situ model, rapid tumor growth and invasion were found, but no tumor metastasis was detected. After transfecting the cell with an induced gene with high expression of S100A4, significant metastasis of para aortic lymph nodes and lungs was found, indicating that S100A4 gene transfection can optimize the bladder tumor metastasis model; It has been confirmed that gene transfection and drug induction have a synergistic effect, such as C-Ha ras mice transfected with the pre cancerous gene being more sensitive to BBN induced bladder tumors.

　　[Model evaluation and application] The in situ model of animal bladder cancer is gradually maturing, and its application scope is also expanded to drug development. At present, tumor cell transplantation model of bladder cancer and chemical carcinogen induced bladder cancer animal model are still widely used. With the development of molecular biotechnology, the animal model of bladder cancer, which is formed by microinjection of target gene fragments into fertilized eggs by means of gene introduction and distribution in somatic cells along with embryonic differentiation, is an important way to study the pathogenesis, biological behavior and treatment of bladder cancer, can more objectively reflect the therapeutic effect of therapeutic factors on bladder cancer, and provide experimental basis for the clinical application of various therapeutic methods for bladder cancer.