dt390与tmtp1融合毒素的构建及其靶向治疗高转移性肿瘤的分析word格式论文.docx

DT390-biTMTP1 融合蛋白处理组裸鼠未发生肝脾转移。DT390-biTMTP1 融合蛋白在荷瘤裸鼠体内的分布与代谢检测提示 DT390-biTMTP1 融合蛋白短时间（注射后 1 小时）内高浓度聚集到皮下瘤组织内，并且持续时间长（注射后 48 小时）。除了 在肝脏（0.5-1 小时）和肾脏（0.5 小时）中一过性出现 DT390-biTMTP1 融合蛋白 阳性表达外，脑组织，心脏组织，脾脏组织，肺组织中都没有出现阳性表达。免 疫组化检测 DT390-biTMTP1 融合蛋白处理的皮下瘤组织中 Ki67 表达明显比对照 组弱，而 Caspase3 和 TUNEL 染色比 PBS 对照组显著增强，提示 DT390-biTMTP1 融合蛋白通过抑制肿瘤细胞增殖，诱导肿瘤细胞坏死发挥抑制裸鼠皮下瘤生长的 作用。结论DT390-biTMTP1 融合蛋白高效靶向杀伤高转移肿瘤及转移灶，提示其具备潜在的 临床应用前景。关键词DT390; TMTP1; 靶向治疗; 肿瘤转移Construction and targeted therapy of highly metastatic tumors by fusion toxins of DT390 linking TMTP1Ph.D. candidate: Ye Shuangmei Supervisor: Prof. Wang ShixuanDepartment of obstetrics and gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstractBackground and purposeMetastasis is one of the most life-threatening aspects of malignancy. Effectively controlling of metastasis could obviously improve the survival periods of patients. Clinical therapies for malignancy include surgery, chemotherapy and radiotherapy. Surgery is the best choice for early malignancy. However, most patients were not in early stage when malignancy was discovered, some even with obvious metastasis. Chemotherapy is a common adjuvant therapy which could eradicate residue lesion or metastatic focus. Adjuvant therapy with surgery and chemotherapy could effectively control various kinds of malignant tumors. But chemotherapy drugs induce evident system toxic and side effects as well as adverse reactions of patients. More over, repeated chemotherapy could easily induce tumor cell became drug resistant, which eliminate drug efficiency. So, scientists tried to produce novel anti-tumor reagents without the disadvantages of chemotherapeutics.In 1906, German scientists proposed “targeted therapy” for the first time. The aim was to increase drug concentration in the local lesion, reduce toxic and side effects, decrease dose of drugs applied, making drugs elicit effects safely and effectively. In the present, molecular targetin