【摘要】：背景與目的:淋巴瘤是原發(fā)于淋巴結(jié)或者淋巴結(jié)外組織或器官的惡性腫瘤,在我國排在惡性腫瘤死亡原因的第11位。淋巴瘤按照病理組織學(xué)的不同分為霍奇金淋巴瘤(Hodgkin's lymphoma,HL)和非霍奇金淋巴瘤(Non-Hodgkin's lymphoma,NHL)。在我國,NHL發(fā)病率遠(yuǎn)高于HL。化學(xué)治療是NHL的主要治療手段,含烷化劑藥物的聯(lián)合化療方案在NHL的治療中得到廣泛應(yīng)用并取得可靠療效。由于化療是全身的系統(tǒng)性治療,不僅殺死腫瘤細(xì)胞,同時(shí)也損傷了許多正常的非腫瘤細(xì)胞,從而產(chǎn)生嚴(yán)重的副作用,造成患者生活質(zhì)量的下降。因而對藥物的敏感性及療效的預(yù)測成為腫瘤個(gè)體化治療的重要環(huán)節(jié)。烷化劑對DNA分子造成損傷時(shí),DNA修復(fù)機(jī)制同時(shí)啟動(dòng),可以保護(hù)細(xì)胞免受化療藥物引起的基因毒性。DNA損傷修復(fù)過程極其復(fù)雜,相關(guān)基因、蛋白和酶只反應(yīng)其中某一個(gè)或幾個(gè)環(huán)節(jié),而DNA修復(fù)率(DNA repair rate,DRR)能夠全面反映個(gè)體的DNA修復(fù)能力,具有成為含烷化劑治療療效預(yù)測指標(biāo)的研究基礎(chǔ)和可行性。本研究采用單細(xì)胞凝膠電泳法(Single cell gel electrophoresis,SCGE)檢測NHL初治患者外周血淋巴細(xì)胞(PBLC)的DNA修復(fù)率(DRR),并分析其與含烷化劑聯(lián)合化療療效的關(guān)系,為NHL患者含烷化劑聯(lián)合化療的敏感性及近期療效的預(yù)測提供依據(jù)。方法:采用單細(xì)胞凝膠電泳法檢測30例NHL患者(腫瘤組)PBLC的DRR,并選取20例非腫瘤患者作為對照(對照組)。腫瘤組接受含環(huán)磷酰胺聯(lián)合方案化療并于4周期后評價(jià)療效,分析腫瘤組和對照組在環(huán)磷酰胺暴露前與暴露且修復(fù)后的DRR及腫瘤組DRR與臨床病理特征及含烷化劑聯(lián)合化療療效的相關(guān)性。結(jié)果:利用尾長(TL)(Z=4.464,P=0.000)和尾相(TM)(Z=3.828,P=0.000)檢測腫瘤組PBLC的DRR均低于對照組。腫瘤組PBLC的DRR與年齡、性別、ECOG評分、臨床分期、LDH值、ki-67增值指數(shù)和是否飲酒均無關(guān)(P0.05)。30例NHL患者中CR 4例、PR 14例、SD 10例、PD 2例,客觀有效率(ORR)為60.0%,疾病控制率(DCR)為93.3%。以TL評價(jià)DRR提示DRR與化療療效呈負(fù)相關(guān)(r=-0.409,p=0.025),以TM評價(jià)DRR提示DRR與化療療效無關(guān)(r=-0.224,p=0.234)。結(jié)論:非霍奇金淋巴瘤患者較非腫瘤患者DNA修復(fù)能力降低,DRR與非霍奇金淋巴瘤患者含烷化劑聯(lián)合化療近期療效呈負(fù)相關(guān)。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R733.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 劉明澄,李崇惠;DNA修復(fù)功能與衰老[J];老年學(xué)雜志;1986年01期

2 王肖鵬,蔣左庶,胡以平,程滸君,楊連生;干擾素對絲裂霉素C誘發(fā)的姊妹染色單體互換和紫外線誘發(fā)的DNA修復(fù)合成影響的研究[J];第二軍醫(yī)大學(xué)學(xué)報(bào);1985年06期

3 葛煒;程吟梅;尹亞萍;鐘繁;;急性淋巴細(xì)胞白血病患者外周血原始淋巴細(xì)胞DNA修復(fù)功能的初步研究[J];科技通報(bào);1991年06期

4 蔣祝昌;XRCC1與DNA修復(fù)[J];國外醫(yī)學(xué).生物醫(yī)學(xué)工程分冊;2003年05期

5 趙實(shí)誠;DNA修復(fù)與急性非淋巴細(xì)胞性白血病幼稚細(xì)胞的DNA修復(fù)測定[J];北京醫(yī)學(xué);1985年04期

6 夏瑩;周東波;胡成平;;DNA修復(fù)與順鉑耐藥[J];國際病理科學(xué)與臨床雜志;2006年04期

7 龍喜帶;唐月浩;曲德英;馬韻;;黃曲霉毒素B_1毒性及其發(fā)揮與DNA修復(fù)(修復(fù)相關(guān)酶)[J];右江民族醫(yī)學(xué)院學(xué)報(bào);2006年02期

8 吳燕;王金兵;龔惠民;;乙肝病毒感染對DNA修復(fù)功能的影響[J];天津醫(yī)藥;1991年08期

9 林東昕;代謝多態(tài)和DNA修復(fù)多態(tài)與癌癥易感性[J];癌癥;1997年05期

10 李晉濤,劉昕,吳玉章;p53基因與DNA修復(fù)[J];國外醫(yī)學(xué)(分子生物學(xué)分冊);2001年03期

相關(guān)會(huì)議論文 前3條

1 隋建麗;劉秀林;胡迎春;金璀珍;周平坤;吳德昌;;輻射誘發(fā)人支氣管上皮細(xì)胞惡性轉(zhuǎn)化亞克隆的細(xì)胞遺傳和DNA修復(fù)研究[A];中國毒理學(xué)會(huì)第三屆全國學(xué)術(shù)會(huì)議論文（摘要）集[C];2001年

2 胡宇;Elizabeth T.Snow;;砷對人角化細(xì)胞DNA修復(fù)和GSH水平及相關(guān)酶活性的調(diào)節(jié)[A];面向21世紀(jì)的科技進(jìn)步與社會(huì)經(jīng)濟(jì)發(fā)展（下冊）[C];1999年

3 尹嬌楊;Ulla Vogel;Lars Bolund;Bjorn A．Nexo;;丹麥高加索人染色體19q13．2-3區(qū)域DNA修復(fù)等基因SNPs：連鎖不平衡及其與基底細(xì)胞癌易感性研究[A];第六次全國醫(yī)學(xué)遺傳學(xué)學(xué)術(shù)會(huì)議文摘匯編[C];2005年

相關(guān)博士學(xué)位論文 前5條

1 路玫;針灸對環(huán)磷酰胺小鼠骨髓細(xì)胞DNA修復(fù)相關(guān)機(jī)制的動(dòng)態(tài)研究[D];湖北中醫(yī)學(xué)院;2008年

2 樓建林;癌癥患者遺傳不穩(wěn)定性的體內(nèi)外研究及其與四個(gè)DNA修復(fù)相關(guān)蛋白的關(guān)系[D];浙江大學(xué);2007年

3 丁佩劍;DNA修復(fù)通路基因多態(tài)位點(diǎn)與乳腺癌發(fā)病風(fēng)險(xiǎn)在中國北方漢族女性人群中的遺傳關(guān)聯(lián)研究[D];河北醫(yī)科大學(xué);2015年

4 高冠軍;耐輻射球菌DNA修復(fù)開關(guān)基因pprI的研究[D];浙江大學(xué);2005年

5 楊青山;DNA修復(fù)蛋白Ku80在人食管癌發(fā)生發(fā)展中的作用研究[D];中國協(xié)和醫(yī)科大學(xué);2008年

相關(guān)碩士學(xué)位論文 前10條

1 王丹丹;DNA修復(fù)率與晚期消化道腫瘤含鉑化療方案療效相關(guān)性的研究[D];安徽醫(yī)科大學(xué);2015年

2 范開杰;肺腺癌DNA修復(fù)通路與NFκB1基因的相關(guān)性研究[D];中國人民解放軍醫(yī)學(xué)院;2015年

3 莊妍;DNA修復(fù)率與非霍奇金淋巴瘤含烷化劑聯(lián)合化療療效的相關(guān)性研究[D];安徽醫(yī)科大學(xué);2016年

4 郭子衣;艾灸促進(jìn)HCC癌前病變大鼠肝細(xì)胞DNA修復(fù)作用研究[D];成都中醫(yī)藥大學(xué);2006年

5 陳寒春;膠質(zhì)瘤組織中DNA修復(fù)相關(guān)基因表達(dá)研究[D];蘇州大學(xué);2003年

6 卜秀華;子宮內(nèi)膜癌發(fā)生過程中DNA修復(fù)蛋白表達(dá)的意義[D];大連醫(yī)科大學(xué);2007年

7 邵超;DNA修復(fù)相關(guān)基因在鎘亞慢性暴露大鼠中的表達(dá)改變[D];廣州醫(yī)學(xué)院;2012年

8 張喬;DNA修復(fù)蛋白XPF影響腎癌細(xì)胞順鉑耐藥的作用與機(jī)制研究[D];第三軍醫(yī)大學(xué);2014年

9 駱海軍;DNA修復(fù)相關(guān)基因甲基化與肺癌A549細(xì)胞順鉑化療耐藥的相關(guān)性[D];貴陽醫(yī)學(xué)院;2014年

10 劉曉林;擬南芥DNA修復(fù)蛋白MSH5在減數(shù)分裂過程中的功能研究[D];中國農(nóng)業(yè)科學(xué)院;2008年

，

本文編號：2255014