尖銳濕疣亞臨床感染的臨床治療及實驗研究
發(fā)布時間：2018-09-12 08:15
【摘要】：背景:尖銳濕疣(condyloma acuminatum,CA)是由人類乳頭瘤病毒(human papilloma virus,HPV)感染引起的一種常見性傳播疾病,發(fā)病率高,約為70/10萬,僅次于非淋菌性尿道炎而居第二位。目前采用分子生物學(xué)技術(shù)將HPV分為100多種亞型,引起尖銳濕疣的病毒主要是HPV-6、11、16、18等亞型。HPV主要感染上皮組織,近來大量文獻(xiàn)及基礎(chǔ)臨床研究已充分肯定HPV在肛門生殖器癌發(fā)生的致病作用,如HPV-16、18、45、56型是最常見導(dǎo)致宮頸癌的亞型。 絕大多數(shù)肛門生殖道HPV感染是潛伏感染或亞臨床感染,有研究發(fā)現(xiàn)90%以上的CA患者有亞臨床感染,它們是CA復(fù)發(fā)的主要原因之一。傳統(tǒng)療法一般僅祛除肉眼所見的疣體,但副作用較大。近來國內(nèi)外研究表明5-氨基酮戊酸光動力療法(ALA-PDT)已成功用于CA的治療,它對增生旺盛的細(xì)胞(包括亞臨床感染的細(xì)胞)有選擇性殺傷作用,而對周圍正常細(xì)胞無明顯影響。 MUC4是一種高分子量的跨膜糖蛋白,最近成為多種惡性腫瘤診斷、預(yù)后和治療的新指標(biāo)。近兩年Subhankar Chakraborty等在一項研究中發(fā)現(xiàn)從正常宮頸到宮頸上皮內(nèi)瘤形成再到宮頸癌,宮頸上皮細(xì)胞MUC4的表達(dá)逐漸增強(qiáng),且既往研究發(fā)現(xiàn)90%以上的宮頸癌組織中可查到HPV,去年Subhankar Chakraborty等在一項研究中發(fā)現(xiàn)大約50%的外陰CA皮損中MUC4表達(dá)強(qiáng)烈,他們認(rèn)為HPV和MUC4之間有種新聯(lián)系。 目的:研究CA亞臨床感染的治療,包括治療方法的選擇及不同治療方法對CA復(fù)發(fā)的影響,從而為CA亞臨床感染的診斷和治療提供更科學(xué)的方法,最終減少CA的復(fù)發(fā);研究外陰CA臨床及亞臨床組織中MUC4 mRNA及MUC4蛋白的表達(dá)情況,探討MUC4在外陰CA增殖及癌變中的作用。 方法:(1)臨床研究對深圳市慢性病防治中心皮膚性病科門診接收的初診CA患者,行醋酸白試驗和電子陰道鏡檢查,或部分行組織病理檢查,確診亞臨床感染(SPI)患者,亞臨床感染陽性率約為90.87%;92例有亞臨床感染的CA患者首先用CO_2激光去除臨床皮損,再分別采用ALA-PDT與CO_2激光治療CA亞臨床感染組織,經(jīng)卡方檢驗及l(fā)ogistic回歸分析方法對兩種治療方法的療效和復(fù)發(fā)情況進(jìn)行比較。(2)實驗研究分別采用逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)及免疫組化染色方法檢測外陰CA臨床、亞臨床組織與正常包皮組織中MUC4 mRNA及其蛋白的表達(dá)情況,用導(dǎo)流雜交技術(shù)檢測HPV亞型。 結(jié)果:(1)CO_2激光治療組的痊愈率為84.3%,半年后復(fù)發(fā)率為15.7%;ALA-PDT組的痊愈率為90.2%,半年后復(fù)發(fā)率為9.8%;經(jīng)統(tǒng)計學(xué)分析,兩種治療方法的痊愈率、復(fù)發(fā)率差異無統(tǒng)計學(xué)意義。(2)外陰CA臨床及亞臨床組織各32例中MUC4 mRNA陽性表達(dá)分別為19例、18例,兩者的MUC4 mRNA陽性表達(dá)差異無統(tǒng)計學(xué)意義(χ~2=0.064, P0.05)。外陰CA臨床及亞臨床組織各32例中MUC4蛋白陽性表達(dá)分別為17例、13例,兩者的MUC4蛋白陽性表達(dá)差異無統(tǒng)計學(xué)意義(χ~2=1.004, P0.05)。32例外陰CA臨床組織中MUC4 mRNA與MUC4蛋白共同陽性表達(dá)的8例,而32例亞臨床組織中MUC4mRNA與MUC4蛋白共同陽性表達(dá)的9例,兩者間表達(dá)差異無統(tǒng)計學(xué)意義(χ~2=0.08, P0.05)。CA主要以HPV-6、11型感染為主,MUC4蛋白及mRNA的陽性表達(dá)與亞型無關(guān)。 結(jié)論:(1) CO_2激光治療組與ALA-PDT組的痊愈率、最終復(fù)發(fā)率差異無統(tǒng)計學(xué)意義;但ALA-PDT組在安全性方面明顯優(yōu)于CO_2激光組;(2)CA患者臨床及亞臨床組織中MUC4 mRNA及蛋白水平均表達(dá)增強(qiáng),可能與CA過度增殖及癌變有關(guān)。
[Abstract]:BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus (HPV) infection, with a high incidence of about 70/100 000, second only to non-gonococcal urethritis. At present, HPV is divided into more than 100 subtypes by molecular biology technology, causing condyloma acuminatum acuminatum. HPV-6,11,16,18 are the main subtypes of HPV. HPV mainly infects epithelial tissues. Recently, a large number of literatures and basic clinical studies have fully confirmed the role of HPV in the pathogenesis of anogenital cancer, such as HPV-16,18,45,56 is the most common subtype of cervical cancer.
The majority of HPV infection in the anal and reproductive tract is latent infection or subclinical infection. Studies have found that more than 90% of CA patients have subclinical infection, which is one of the main causes of CA recurrence. It has been successfully used in the treatment of CA. It has selective killing effect on proliferative cells, including subclinical infected cells, but has no obvious effect on peripheral normal cells.
MUC4, a high molecular weight transmembrane glycoprotein, has recently become a new marker for the diagnosis, prognosis and treatment of many malignant tumors. Subhankar Chakraborty et al. found in a recent two years that the expression of MUC4 in cervical epithelial cells increased gradually from normal cervix to cervical intraepithelial neoplasia to cervical cancer, and more than 90% of previous studies have found that the expression of MUC4 in cervical epithelial cells HPV is found in about 50% of vulvar CA lesions in a study last year by Subhankar Chakraborty et al. They believe there is a new link between HPV and MUC4.
Objective: To study the treatment of subclinical infection of CA, including the choice of treatment methods and the influence of different treatment methods on the recurrence of CA, so as to provide a more scientific method for the diagnosis and treatment of subclinical infection of CA, and ultimately reduce the recurrence of CA. The role of Yin CA in proliferation and carcinogenesis.
Methods: (1) The positive rate of subclinical infection (SPI) was about 90.87% in the newly diagnosed CA patients received by the dermatology and Venereology clinic of Shenzhen Chronic Disease Prevention and Treatment Center. 92 CA patients with subclinical infection were first diagnosed by CO_2 laser. After removing the clinical lesions, the subclinical infected tissues of CA were treated with ALA-PDT and CO_2 laser respectively. The curative effect and recurrence of the two methods were compared by Chi-square test and logistic regression analysis. (2) The clinical features of vulva CA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of MUC4 mRNA and its protein in subclinical and normal prepuce tissues was detected by flow-through hybridization.
Results: (1) The cure rate of CO_2 laser treatment group was 84.3%, and the recurrence rate was 15.7% after half a year; the cure rate of ALA-PDT group was 90.2%, and the recurrence rate was 9.8% after half a year; statistical analysis showed that there was no significant difference in the recovery rate and recurrence rate between the two treatment methods. (2) The positive expression of MUC4 mRNA in vulvar CA clinical and subclinical tissues was 19 cases respectively. There was no significant difference in MUC4 mRNA expression between the two groups (_~2=0.064, P 0.05). The positive expression of MUC4 protein in vulvar CA clinical and subclinical tissues was 17 cases and 13 cases respectively. There was no significant difference in MUC4 protein expression between the two groups (_~2=1.004, P 0.05). There was no significant difference between the positive expression of MUC4 mRNA and MUC4 protein in 9 of 32 subclinical tissues (_~2=0.08,P 0.05). HPV-6,11 infection was predominant in CA, but the positive expression of MUC4 protein and mRNA was not related to the subtype.
Conclusion: (1) There was no significant difference in the cure rate and the final recurrence rate between the CO_2 laser treatment group and the ALA-PDT group, but the safety of the ALA-PDT group was significantly better than that of the CO_2 laser group; (2) The expression of MUC4 mRNA and protein in the clinical and subclinical tissues of CA patients was enhanced, which may be related to CA hyperplasia and carcinogenesis.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R752.53
[Abstract]:BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus (HPV) infection, with a high incidence of about 70/100 000, second only to non-gonococcal urethritis. At present, HPV is divided into more than 100 subtypes by molecular biology technology, causing condyloma acuminatum acuminatum. HPV-6,11,16,18 are the main subtypes of HPV. HPV mainly infects epithelial tissues. Recently, a large number of literatures and basic clinical studies have fully confirmed the role of HPV in the pathogenesis of anogenital cancer, such as HPV-16,18,45,56 is the most common subtype of cervical cancer.
The majority of HPV infection in the anal and reproductive tract is latent infection or subclinical infection. Studies have found that more than 90% of CA patients have subclinical infection, which is one of the main causes of CA recurrence. It has been successfully used in the treatment of CA. It has selective killing effect on proliferative cells, including subclinical infected cells, but has no obvious effect on peripheral normal cells.
MUC4, a high molecular weight transmembrane glycoprotein, has recently become a new marker for the diagnosis, prognosis and treatment of many malignant tumors. Subhankar Chakraborty et al. found in a recent two years that the expression of MUC4 in cervical epithelial cells increased gradually from normal cervix to cervical intraepithelial neoplasia to cervical cancer, and more than 90% of previous studies have found that the expression of MUC4 in cervical epithelial cells HPV is found in about 50% of vulvar CA lesions in a study last year by Subhankar Chakraborty et al. They believe there is a new link between HPV and MUC4.
Objective: To study the treatment of subclinical infection of CA, including the choice of treatment methods and the influence of different treatment methods on the recurrence of CA, so as to provide a more scientific method for the diagnosis and treatment of subclinical infection of CA, and ultimately reduce the recurrence of CA. The role of Yin CA in proliferation and carcinogenesis.
Methods: (1) The positive rate of subclinical infection (SPI) was about 90.87% in the newly diagnosed CA patients received by the dermatology and Venereology clinic of Shenzhen Chronic Disease Prevention and Treatment Center. 92 CA patients with subclinical infection were first diagnosed by CO_2 laser. After removing the clinical lesions, the subclinical infected tissues of CA were treated with ALA-PDT and CO_2 laser respectively. The curative effect and recurrence of the two methods were compared by Chi-square test and logistic regression analysis. (2) The clinical features of vulva CA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of MUC4 mRNA and its protein in subclinical and normal prepuce tissues was detected by flow-through hybridization.
Results: (1) The cure rate of CO_2 laser treatment group was 84.3%, and the recurrence rate was 15.7% after half a year; the cure rate of ALA-PDT group was 90.2%, and the recurrence rate was 9.8% after half a year; statistical analysis showed that there was no significant difference in the recovery rate and recurrence rate between the two treatment methods. (2) The positive expression of MUC4 mRNA in vulvar CA clinical and subclinical tissues was 19 cases respectively. There was no significant difference in MUC4 mRNA expression between the two groups (_~2=0.064, P 0.05). The positive expression of MUC4 protein in vulvar CA clinical and subclinical tissues was 17 cases and 13 cases respectively. There was no significant difference in MUC4 protein expression between the two groups (_~2=1.004, P 0.05). There was no significant difference between the positive expression of MUC4 mRNA and MUC4 protein in 9 of 32 subclinical tissues (_~2=0.08,P 0.05). HPV-6,11 infection was predominant in CA, but the positive expression of MUC4 protein and mRNA was not related to the subtype.
Conclusion: (1) There was no significant difference in the cure rate and the final recurrence rate between the CO_2 laser treatment group and the ALA-PDT group, but the safety of the ALA-PDT group was significantly better than that of the CO_2 laser group; (2) The expression of MUC4 mRNA and protein in the clinical and subclinical tissues of CA patients was enhanced, which may be related to CA hyperplasia and carcinogenesis.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R752.53
【共引文獻(xiàn)】
相關(guān)期刊論文 前10條
1 劉文沛;胃癌的光動力治療進(jìn)展[J];中國醫(yī)師雜志;2003年11期
2 潘武;張南征;駱曉梅;;光動力治療對食管癌患者T淋巴細(xì)胞亞群的影響[J];第四軍醫(yī)大學(xué)學(xué)報;2005年23期
3 盧娉霞;鄒紅;祝先進(jìn);張e，
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