DNA修复率与非霍奇金淋巴瘤含烷化剂联合化疗疗效的相关性研究

发布时间：2018-10-05 21:58

【摘要】：背景与目的:淋巴瘤是原发于淋巴结或者淋巴结外组织或器官的恶性肿瘤,在我国排在恶性肿瘤死亡原因的第11位。淋巴瘤按照病理组织学的不同分为霍奇金淋巴瘤(Hodgkin's lymphoma,HL)和非霍奇金淋巴瘤(Non-Hodgkin's lymphoma,NHL)。在我国,NHL发病率远高于HL。化学治疗是NHL的主要治疗手段,含烷化剂药物的联合化疗方案在NHL的治疗中得到广泛应用并取得可靠疗效。由于化疗是全身的系统性治疗,不仅杀死肿瘤细胞,同时也损伤了许多正常的非肿瘤细胞,从而产生严重的副作用,造成患者生活质量的下降。因而对药物的敏感性及疗效的预测成为肿瘤个体化治疗的重要环节。烷化剂对DNA分子造成损伤时,DNA修复机制同时启动,可以保护细胞免受化疗药物引起的基因毒性。DNA损伤修复过程极其复杂,相关基因、蛋白和酶只反应其中某一个或几个环节,而DNA修复率(DNA repair rate,DRR)能够全面反映个体的DNA修复能力,具有成为含烷化剂治疗疗效预测指标的研究基础和可行性。本研究采用单细胞凝胶电泳法(Single cell gel electrophoresis,SCGE)检测NHL初治患者外周血淋巴细胞(PBLC)的DNA修复率(DRR),并分析其与含烷化剂联合化疗疗效的关系,为NHL患者含烷化剂联合化疗的敏感性及近期疗效的预测提供依据。方法:采用单细胞凝胶电泳法检测30例NHL患者(肿瘤组)PBLC的DRR,并选取20例非肿瘤患者作为对照(对照组)。肿瘤组接受含环磷酰胺联合方案化疗并于4周期后评价疗效,分析肿瘤组和对照组在环磷酰胺暴露前与暴露且修复后的DRR及肿瘤组DRR与临床病理特征及含烷化剂联合化疗疗效的相关性。结果:利用尾长(TL)(Z=4.464,P=0.000)和尾相(TM)(Z=3.828,P=0.000)检测肿瘤组PBLC的DRR均低于对照组。肿瘤组PBLC的DRR与年龄、性别、ECOG评分、临床分期、LDH值、ki-67增值指数和是否饮酒均无关(P0.05)。30例NHL患者中CR 4例、PR 14例、SD 10例、PD 2例,客观有效率(ORR)为60.0%,疾病控制率(DCR)为93.3%。以TL评价DRR提示DRR与化疗疗效呈负相关(r=-0.409,p=0.025),以TM评价DRR提示DRR与化疗疗效无关(r=-0.224,p=0.234)。结论:非霍奇金淋巴瘤患者较非肿瘤患者DNA修复能力降低,DRR与非霍奇金淋巴瘤患者含烷化剂联合化疗近期疗效呈负相关。
[Abstract]:Background & objective: lymphoma is the primary malignant tumor in lymph nodes or tissues or organs outside lymph nodes, which ranks 11th among the causes of death of malignant tumors in China. Lymphoma is divided into Hodgkin's lymphoma (Hodgkin's lymphoma,HL) and non Hodgkin's lymphoma (Non-Hodgkin's lymphoma,NHL) according to histopathology. The incidence of NHL in China is much higher than that in HL.. Chemotherapy is the main treatment method of NHL. The combination chemotherapy regimen containing alkylating agent has been widely used in the treatment of NHL and has obtained reliable curative effect. Because chemotherapy is systemic therapy, it not only kills tumor cells, but also injures many normal non-tumor cells, resulting in serious side effects and the decline of patients' quality of life. Therefore, the prediction of drug sensitivity and efficacy has become an important part of individualized tumor therapy. The repair mechanism of DNA molecules caused by alkylating agents is activated simultaneously, which can protect cells from the genetic toxicity caused by chemotherapeutic drugs. The repair process of DNA damage is extremely complicated. The related genes, proteins and enzymes only respond to one or more of them. DNA repair rate (DNA repair rate,DRR) can fully reflect individual DNA repair ability, which is the basis and feasibility of predicting the efficacy of alkylating agent therapy. In this study, single cell gel electrophoresis (Single cell gel electrophoresis,SCGE) was used to detect the DNA repair rate (DRR),) of (PBLC) in peripheral blood lymphocytes of patients with NHL, and to analyze the relationship between the DNA repair rate and the effect of alkylating agent combined with chemotherapy. To provide the basis for the sensitivity of NHL patients with alkylating agent combined with chemotherapy and the prediction of short-term curative effect. Methods: single cell gel electrophoresis was used to detect the DRR, of PBLC in 30 patients with NHL (tumor group) and 20 non-tumor patients as control group (control group). The tumor group received chemotherapy with cyclophosphamide regimen and evaluated the efficacy after 4 cycles. The relationship between DRR before and after exposure and repair of cyclophosphamide and the clinicopathological characteristics of DRR in tumor group and control group as well as the efficacy of alkylating agent combined chemotherapy were analyzed. Results: the DRR of PBLC in the tumor group was lower than that in the control group by using the tail length (TL) (4.464) and the tail phase (TM) (3.828 P0. 000). The DRR of PBLC in tumor group was not related to age, sex and score of ECOG, the value of Ki-67 in clinical stage and whether or not to drink (P0.05). Of the 30 patients with NHL, there were 4 cases of CR with PR and 10 cases of PD with PD. The objective effective rate of (ORR) was 60. 0. The rate of disease control was 93. 3 and the objective effective rate of (ORR) was 60. 0 and the rate of disease control was 93. 3% (P < 0. 05). DRR was negatively correlated with chemotherapeutic efficacy by TL evaluation of DRR (r-0.409), DRR by TM was not correlated with chemotherapeutic effect (r-0.224p0.234). Conclusion: the reduction of DNA repair ability in patients with non-Hodgkin 's lymphoma is negatively correlated with the short-term efficacy of alkylating agents combined with chemotherapy in patients with non-Hodgkin 's lymphoma.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.1

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