靶向EBV-LMP1脱氧核酶提高鼻咽癌放疗敏感性的临床深入研究
发布时间：2018-08-05 14:09
【摘要】： 目的 鼻咽癌是中国常见的恶性上皮性肿瘤,该肿瘤的发生以及进展与EB病毒密切相关。LMP1是EB病毒编码的致瘤蛋白,它抑上皮细胞分化、抗凋亡而导致放疗抵抗。针对该基因的靶向治疗联合放疗有望增加鼻咽癌的局部控制和远期疗效。本课题将能特异性切割LMPl的靶向EBV-LMP1脱氧核酶应用于EBV-LMP1阳性鼻咽癌患者的放疗,在观察该核酶毒副作用的同时,深入研究其对LMP1阳性鼻咽癌的放疗增敏、局部控制和中长期疗效。 方法 严格按照入选条件,将40例EBV-LMP1阳性的鼻咽癌初治患者完全随机化列入两组,在常规根治性放疗的基础上分别在鼻咽肿瘤局部注射脱氧核酶(即综合治疗组：放疗+脱氧核酶)及生理盐水做为空白对照(单纯放疗组),其它处理完全相同,必要时予对症支持处理,不使用免疫增强治疗和其它放疗增敏剂。对两组患者进行毒副作用及疗效观察。毒副反应指标为血液系统毒性、肝肾功能毒性及放疗常见的皮肤粘膜涎腺的急性损伤；并根据多时间点肿瘤体积对比两组的RTR和疗效,并对比两组的生存情况(OS、TTP、TTD)。 结果 1.两组患者一般指标一致性良好,无选择性偏倚。 2.脱氧核酶的临床研究有较好的安全性,无重大安全事情的发生,并且在血象、肝肾功能、粘膜腺体损伤等方面,未增加放疗本身的副反应(p均0.05)。 3.在放疗第5、第7周时,综合治疗组的平均RTR是74.73%、88.01%,单纯放疗组是64.89%、78.94%,增效倍数为1.15、1.11；放疗后3月时,综合治疗组的平均RTR是98.64%,单纯放疗组是89.61%,增效倍数为1.10,综合治疗组均优于单纯放疗组；且RTR3的P值0.05,在放疗后第7周时,综合治疗组肿瘤消退较单纯放疗组明显；并且整个放疗过程中综合治疗组的CR的患者均多于单纯放疗组。在放疗后3个月,放疗组的CR是单纯放疗组的2.2倍,即使是在PR病例的比较中,综合治疗组的瘤体平均消退率也优于单纯放疗组(1.13倍),且比较两组CR、PR的p值=0.0270.05,显示了放疗后3月,综合治疗组肿瘤消退要优于单放组。 4.在随访的观察中,综合治疗组的生存有一定优势,pos=0.692、pTTP=0.041,pTTP=0.102; 2年生存率综合治疗组为85.7%高于单纯放疗组的80.0%,p1,2年生存率=0.737。 结论 1.靶向EBV-LMP1脱氧核酶联合放疗在LMP1阳性鼻咽癌患者的临床研究有较好的安全性,不增加放疗的毒副作用； 2.靶向EBV-LMP1脱氧核酶能提高LMP1阳性鼻咽癌放疗的肿瘤消退率,对控制原发灶有较为明显的疗效,能增加放疗的敏感性； 3.靶向EBV-LMP1脱氧核酶联合放疗能有效控制LMP1阳性鼻咽癌患者的疾病进展。
[Abstract]:Objective Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor in China. The carcinogenesis and progression of nasopharyngeal carcinoma (NPC) is closely related to EBV. LMP1 is a tumorigenic protein encoded by EBV, which inhibits the differentiation of epithelial cells. Anti-apoptosis leads to radiation resistance. Targeted therapy combined with radiotherapy is expected to increase local control and long-term efficacy of nasopharyngeal carcinoma. In this study, EBV-LMP1 deoxyribozyme, which can specifically cut LMPl, was applied to radiotherapy in patients with EBV-LMP1 positive nasopharyngeal carcinoma. The toxicity and side effects of the ribozyme were observed, and the radiosensitization, local control and medium- and long-term efficacy of LMP1 positive nasopharyngeal carcinoma were studied. Methods 40 patients with nasopharyngeal carcinoma (NPC) with EBV-LMP1 positive were randomly assigned to the two groups according to the selected conditions. On the basis of conventional radical radiotherapy, local injection of deoxyribozyme (combined treatment group: radiotherapy deoxyribozyme) and saline as blank control (radiotherapy group) in nasopharyngeal neoplasms, the other treatments were identical. If necessary for symptomatic support treatment, do not use immunoenhancement therapy and other radiotherapy sensitizer. The toxicity and side effects of the two groups were observed. The toxic and side effects were as follows: acute injury of salivary gland of skin and mucous membrane which was common in radiation therapy, and RTR and curative effect of two groups were compared according to tumor volume of multiple time points, and survival status of two groups was compared (OSTTP TTD). Result 1. Two groups of patients with good consistency of general indicators, no selective bias. 2. The clinical study of deoxyribozyme has good safety, no significant safety events, and in the aspects of blood, liver and kidney function, mucosal damage, etc., the side effects of radiotherapy itself were not increased (p 0.05). 3. At the 5th and 7th week of radiotherapy, the average RTR of the combined treatment group was 74.73 and 88.01, and that of the simple radiotherapy group was 64.89 and 78.94, and the increase was 1.15 and 1.11 respectively. The average RTR of the combined treatment group was 98.64 and that of the radiotherapy group was 89.61, and the synergistic factor was 1.10. The combined treatment group was superior to the radiotherapy group, and the P value of RTR3 was 0.05. At the 7th week after radiotherapy, the tumor regression of the combined treatment group was significantly higher than that of the radiotherapy alone group. During the whole radiotherapy process, CR patients in the combined treatment group were more than those in the radiotherapy alone group. At 3 months after radiotherapy, CR in the radiotherapy group was 2.2 times higher than that in the radiotherapy alone group, even in PR cases. The average regression rate of tumor in the combined treatment group was also higher than that in the radiotherapy group (1.13 times), and the P value of CRP PR in the two groups was 0.0270.05, which showed that the tumor regression rate in the combined treatment group was better than that in the radiotherapy group 3 months after radiotherapy. 4. In the follow-up observation, the survival rate of the combined treatment group was 0.692pTTP 0.041pTTP 0.102, and the 2-year survival rate of the combined treatment group was 85.7% higher than that of the radiotherapy group (80.0%), and the 2-year survival rate was 0.73737%. Conclusion 1. The clinical study of targeted EBV-LMP1 deoxyribozyme combined with radiotherapy in LMP1 positive patients with nasopharyngeal carcinoma has good safety and does not increase the toxicity and side effects of radiotherapy. 2. Targeting EBV-LMP1 deoxyribozyme can improve the tumor extinction rate of LMP1 positive nasopharyngeal carcinoma, have obvious effect on the control of primary tumor, and increase the sensitivity of radiotherapy. 3. Targeted EBV-LMP1 deoxyribozyme combined with radiotherapy can effectively control the progression of LMP1 positive nasopharyngeal carcinoma patients.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.63
本文编号：2166026
[Abstract]:Objective Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor in China. The carcinogenesis and progression of nasopharyngeal carcinoma (NPC) is closely related to EBV. LMP1 is a tumorigenic protein encoded by EBV, which inhibits the differentiation of epithelial cells. Anti-apoptosis leads to radiation resistance. Targeted therapy combined with radiotherapy is expected to increase local control and long-term efficacy of nasopharyngeal carcinoma. In this study, EBV-LMP1 deoxyribozyme, which can specifically cut LMPl, was applied to radiotherapy in patients with EBV-LMP1 positive nasopharyngeal carcinoma. The toxicity and side effects of the ribozyme were observed, and the radiosensitization, local control and medium- and long-term efficacy of LMP1 positive nasopharyngeal carcinoma were studied. Methods 40 patients with nasopharyngeal carcinoma (NPC) with EBV-LMP1 positive were randomly assigned to the two groups according to the selected conditions. On the basis of conventional radical radiotherapy, local injection of deoxyribozyme (combined treatment group: radiotherapy deoxyribozyme) and saline as blank control (radiotherapy group) in nasopharyngeal neoplasms, the other treatments were identical. If necessary for symptomatic support treatment, do not use immunoenhancement therapy and other radiotherapy sensitizer. The toxicity and side effects of the two groups were observed. The toxic and side effects were as follows: acute injury of salivary gland of skin and mucous membrane which was common in radiation therapy, and RTR and curative effect of two groups were compared according to tumor volume of multiple time points, and survival status of two groups was compared (OSTTP TTD). Result 1. Two groups of patients with good consistency of general indicators, no selective bias. 2. The clinical study of deoxyribozyme has good safety, no significant safety events, and in the aspects of blood, liver and kidney function, mucosal damage, etc., the side effects of radiotherapy itself were not increased (p 0.05). 3. At the 5th and 7th week of radiotherapy, the average RTR of the combined treatment group was 74.73 and 88.01, and that of the simple radiotherapy group was 64.89 and 78.94, and the increase was 1.15 and 1.11 respectively. The average RTR of the combined treatment group was 98.64 and that of the radiotherapy group was 89.61, and the synergistic factor was 1.10. The combined treatment group was superior to the radiotherapy group, and the P value of RTR3 was 0.05. At the 7th week after radiotherapy, the tumor regression of the combined treatment group was significantly higher than that of the radiotherapy alone group. During the whole radiotherapy process, CR patients in the combined treatment group were more than those in the radiotherapy alone group. At 3 months after radiotherapy, CR in the radiotherapy group was 2.2 times higher than that in the radiotherapy alone group, even in PR cases. The average regression rate of tumor in the combined treatment group was also higher than that in the radiotherapy group (1.13 times), and the P value of CRP PR in the two groups was 0.0270.05, which showed that the tumor regression rate in the combined treatment group was better than that in the radiotherapy group 3 months after radiotherapy. 4. In the follow-up observation, the survival rate of the combined treatment group was 0.692pTTP 0.041pTTP 0.102, and the 2-year survival rate of the combined treatment group was 85.7% higher than that of the radiotherapy group (80.0%), and the 2-year survival rate was 0.73737%. Conclusion 1. The clinical study of targeted EBV-LMP1 deoxyribozyme combined with radiotherapy in LMP1 positive patients with nasopharyngeal carcinoma has good safety and does not increase the toxicity and side effects of radiotherapy. 2. Targeting EBV-LMP1 deoxyribozyme can improve the tumor extinction rate of LMP1 positive nasopharyngeal carcinoma, have obvious effect on the control of primary tumor, and increase the sensitivity of radiotherapy. 3. Targeted EBV-LMP1 deoxyribozyme combined with radiotherapy can effectively control the progression of LMP1 positive nasopharyngeal carcinoma patients.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.63
【引证文献】
相关硕士学位论文 前1条
1 何凤姣;鼻咽癌的分子靶向治疗联合放疗的临床实验研究[D];中南大学;2011年
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