动物造模,药效评价,人体肿瘤术后转移 z-bio 2024-07-24 403

　　It is difficult to establish a subcutaneous transplant tumor metastasis model mainly because the tumor is implanted subcutaneously, and its microenvironment is not conducive to the expression of malignant tumor biological characteristics, especially metastasis characteristics. Therefore, it takes a long time for human tumors to metastasize in nude mice. When the tumor has not yet metastasized or the metastasis is not obvious, the excessive tumor load at the inoculation site causes animal death, and the biological characteristics of the tumor are not fully expressed during the tumor bearing life of mice. That is to say, in general, most animals transplanted with subcutaneous tumors eventually die of exhaustion due to the size of the subcutaneous tumor, rather than death due to tumor metastasis. In clinical practice, the reason why the 5-year survival rate of patients undergoing surgical treatment for malignant tumors is very low is because the tumor has already undergone distant or micro metastasis when the primary tumor is eradicated. In response to the secondary distant organ metastasis after tumor eradication surgery in clinical practice, the laboratory where the author is located established a nude mouse model of human colon cancer postoperative metastasis by simulating clinical use of surgical resection of tumors. The method was to take human colon adenocarcinoma cell line HCT-116 and inoculate it subcutaneously on the right back near the axilla of nude mice. After passage in vivo, subcutaneous transplanted tumors were obtained. Four weeks later, when mild necrosis of the tumor appeared, 15 nude mice were randomly selected for routine anesthesia, and tumor tissue was surgically removed. The remaining 13 nude mice were not treated and continued to be observed. At 9 weeks of untreated nude mice, the tumor necrosis was severe, and some animals showed cachexia. Anatomical examination showed a lung metastasis rate of 23% (3/13), which was basically normal under naked eye observation and was only detected by microscopic examination; The surgical site of nude mice with tumor resection showed no tumor recurrence, and the animals were in good health. After 17 weeks, the lung metastasis rate reached 100% (15/15), lymph node metastasis rate was 100% (15/15), and spleen metastasis rate was 33.3% (5/15). The key to establishing a postoperative metastasis model is to completely remove the tumor and avoid local recurrence; The second is to choose an appropriate surgical resection time. Cutting the tumor too early may not fully express its metastatic characteristics, while cutting it too late may result in the tumor becoming too large and necrotic. After surgery, it is easy to cause large wounds, bleeding, and incomplete tumor resection, leading to infection, bleeding, local recurrence, and even death, which affects the success of the model; Thirdly, it is necessary to observe for a sufficient period of time in experiments. Generally, animals with high metastasis rates can only appear after more than 10 weeks of tumor resection.

　　The animal model of human tumor postoperative metastasis simulates the process of distant metastasis after clinical tumor eradication surgery, providing an ideal animal model for studying the mechanism of tumor metastasis and postoperative anti metastasis treatment. We found that in addition to establishing a postoperative metastasis model through subcutaneous transplantation of human colon adenocarcinoma cell line HCT-116 in nude mice, various human cancer cell lines such as non-small cell lung cancer H460, poorly differentiated gastric adenocarcinoma MKN-45, melanoma A375, etc. have the characteristic of postoperative metastasis. According to the idea that surgical resection of tumors can prolong the lifespan of tumor bearing animals and fully express tumor metastasis characteristics, it is also possible to establish an animal model of metastasis after in situ transplantation, which not only improves the metastasis rate of tumors, but also is more in line with the actual clinical situation of tumor patients. For example, after human liver cancer is transplanted in situ into nude mice, if the tumor bearing liver lobe is removed at an appropriate time, lung and lymph node metastasis may occur after a period of time; Human kidney cancer was transplanted in situ into nude mice, and after tumor growth, the kidney on the tumor bearing side was removed. Several weeks later, distant organ metastasis may occur in nude mice; Human cancer cells were seeded on the inner side of the paw pads of nude mice. After a period of tumor growth, the tumor bearing lower limbs were removed, which can increase the metastasis rate of lymph nodes and lungs.