【摘要】： 目的 鼻咽癌是中國(guó)常見的惡性上皮性腫瘤,該腫瘤的發(fā)生以及進(jìn)展與EB病毒密切相關(guān)。LMP1是EB病毒編碼的致瘤蛋白,它抑上皮細(xì)胞分化、抗凋亡而導(dǎo)致放療抵抗。針對(duì)該基因的靶向治療聯(lián)合放療有望增加鼻咽癌的局部控制和遠(yuǎn)期療效。本課題將能特異性切割LMPl的靶向EBV-LMP1脫氧核酶應(yīng)用于EBV-LMP1陽(yáng)性鼻咽癌患者的放療,在觀察該核酶毒副作用的同時(shí),深入研究其對(duì)LMP1陽(yáng)性鼻咽癌的放療增敏、局部控制和中長(zhǎng)期療效。 方法 嚴(yán)格按照入選條件,將40例EBV-LMP1陽(yáng)性的鼻咽癌初治患者完全隨機(jī)化列入兩組,在常規(guī)根治性放療的基礎(chǔ)上分別在鼻咽腫瘤局部注射脫氧核酶(即綜合治療組：放療+脫氧核酶)及生理鹽水做為空白對(duì)照(單純放療組),其它處理完全相同,必要時(shí)予對(duì)癥支持處理,不使用免疫增強(qiáng)治療和其它放療增敏劑。對(duì)兩組患者進(jìn)行毒副作用及療效觀察。毒副反應(yīng)指標(biāo)為血液系統(tǒng)毒性、肝腎功能毒性及放療常見的皮膚粘膜涎腺的急性損傷；并根據(jù)多時(shí)間點(diǎn)腫瘤體積對(duì)比兩組的RTR和療效,并對(duì)比兩組的生存情況(OS、TTP、TTD)。 結(jié)果 1.兩組患者一般指標(biāo)一致性良好,無選擇性偏倚。 2.脫氧核酶的臨床研究有較好的安全性,無重大安全事情的發(fā)生,并且在血象、肝腎功能、粘膜腺體損傷等方面,未增加放療本身的副反應(yīng)(p均0.05)。 3.在放療第5、第7周時(shí),綜合治療組的平均RTR是74.73%、88.01%,單純放療組是64.89%、78.94%,增效倍數(shù)為1.15、1.11；放療后3月時(shí),綜合治療組的平均RTR是98.64%,單純放療組是89.61%,增效倍數(shù)為1.10,綜合治療組均優(yōu)于單純放療組；且RTR3的P值0.05,在放療后第7周時(shí),綜合治療組腫瘤消退較單純放療組明顯；并且整個(gè)放療過程中綜合治療組的CR的患者均多于單純放療組。在放療后3個(gè)月,放療組的CR是單純放療組的2.2倍,即使是在PR病例的比較中,綜合治療組的瘤體平均消退率也優(yōu)于單純放療組(1.13倍),且比較兩組CR、PR的p值=0.0270.05,顯示了放療后3月,綜合治療組腫瘤消退要優(yōu)于單放組。 4.在隨訪的觀察中,綜合治療組的生存有一定優(yōu)勢(shì),pos=0.692、pTTP=0.041,pTTP=0.102; 2年生存率綜合治療組為85.7%高于單純放療組的80.0%,p1,2年生存率=0.737。 結(jié)論 1.靶向EBV-LMP1脫氧核酶聯(lián)合放療在LMP1陽(yáng)性鼻咽癌患者的臨床研究有較好的安全性,不增加放療的毒副作用； 2.靶向EBV-LMP1脫氧核酶能提高LMP1陽(yáng)性鼻咽癌放療的腫瘤消退率,對(duì)控制原發(fā)灶有較為明顯的療效,能增加放療的敏感性； 3.靶向EBV-LMP1脫氧核酶聯(lián)合放療能有效控制LMP1陽(yáng)性鼻咽癌患者的疾病進(jìn)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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R739.63

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 何鳳姣;鼻咽癌的分子靶向治療聯(lián)合放療的臨床實(shí)驗(yàn)研究[D];中南大學(xué);2011年

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本文編號(hào)：2166026