本文選題：蕈樣肉芽腫 + 細(xì)胞轉(zhuǎn)化��； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景蕈樣肉芽腫(MF)是最常見的皮膚淋巴瘤,約占皮膚T淋巴瘤的50%。MF區(qū)別于其他類型皮膚淋巴瘤的一個最顯著特征,是其具有相對惰性的生物學(xué)行為,即臨床表現(xiàn)為斑片乃至斑塊的皮損進(jìn)展極其緩慢,可持續(xù)數(shù)年至數(shù)十年不等。然而,一旦出現(xiàn)進(jìn)展期皮損如斑塊或腫瘤,則顯示顯著的侵襲性生物學(xué)行為,包括累及外周血、淋巴結(jié)或內(nèi)臟器官。探尋一種能夠預(yù)判MF生物學(xué)行為轉(zhuǎn)化的標(biāo)志物,對MF的臨床管理和治療選擇極其重要。IL-13作為Th2相關(guān)細(xì)胞因子,可以直接促進(jìn)腫瘤增殖和/或協(xié)同抑制腫瘤免疫監(jiān)視的作用;而其受體IL-13Rα1及IL-13Rα2是一種新近發(fā)現(xiàn)的血源性受體家族成員之一,與IL-13具有相對高度專一的親和力,有待成為特異性的、有前途的腫瘤基因治療靶點。目的本研究通過檢測分析不同時期MF患者皮損中IL-13及其受體的表達(dá),以期為MF生物學(xué)行為轉(zhuǎn)化與進(jìn)展提供一種新的標(biāo)記和候選的分子治療靶點。方法收集杭州市第三人民醫(yī)院皮膚科2010年1月-2016年3月經(jīng)臨床、病理、免疫表型和/或T細(xì)胞受體基因重排檢測確診的MF石蠟組織標(biāo)本34例,根據(jù)TNM分期分為ⅠA期5例,ⅠB期9例,ⅡA期17例和ⅡB期3例。另外選擇正常皮膚組織10例作為對照。應(yīng)用免疫組化方法分別檢測IL-13、IL-13Rα1及IL-13Rα2的表達(dá)。另外,應(yīng)用MTS法檢測加入不同濃度IL-13后MF細(xì)胞株Hut-102細(xì)胞的吸光度值,分析IL-13對Hut-102細(xì)胞的增殖作用;應(yīng)用流式細(xì)胞術(shù)檢測加入IL-13后Hut-102細(xì)胞周期的變化。結(jié)果IL-13、IL-13Rα1和IL-13Rα2表達(dá)于各期MF皮損組織的異型淋巴樣細(xì)胞和親表皮性淋巴樣細(xì)胞,尤其IL-13Rα2幾乎高表達(dá)于所有的MF皮損組織。正常皮膚組織及淋巴細(xì)胞均不表達(dá)IL-13及其受體。隨著MF病程的進(jìn)展,皮損組織IL-13及其受體表達(dá)率升高。Ⅰ期MF皮損IL-13、IL-13Rα1及IL-13Rα2的表達(dá)率均顯著低于Ⅱ期MF皮損,差異均有統(tǒng)計學(xué)意義(Ⅰ、Ⅱ期MF皮損IL-13的表達(dá)率分別為10.00±3.14、27.50±11.00,P0.05;Ⅰ、Ⅱ期MF皮損IL-13Rα1的表達(dá)率分別為21.43±6.88、39.45±9.43,P0.05;Ⅰ、Ⅱ期MF皮損IL-13Rα2的表達(dá)率分別為31.14±6.38、44.40±11.15,P0.05),但在ⅠA期與ⅠB期之間以及ⅡA期與ⅡB期之間差異均沒有統(tǒng)計學(xué)意義(均P0.05)。IL-13對體外培養(yǎng)的Hut-102細(xì)胞有明顯的增殖促進(jìn)作用,且會隨著劑量的增大產(chǎn)生的促進(jìn)作用增強。流式細(xì)胞術(shù)結(jié)果顯示50ng/ml濃度以上的IL-13均可使Hut-102細(xì)胞G0/G1期細(xì)胞比例減少,位與S期的細(xì)胞比例增多,而對G2/M期無明顯影響。結(jié)論IL-13及其受體尤其是IL-13Rα2,有期成為MF早期診斷和生物學(xué)行為預(yù)判的標(biāo)志物。IL-13對體外培養(yǎng)的Hut-102細(xì)胞有促進(jìn)增殖的作用,能使促進(jìn)其盡快從G0/G1期進(jìn)入S期。
[Abstract]:Background mycosis fungoides (MF) is the most common cutaneous lymphoma, accounting for about 50% of cutaneous T lymphoma. MF is one of the most prominent characteristics of other types of cutaneous lymphoma, and it has relatively inert biological behavior. That is, the clinical manifestations of plaque and plaque skin damage progress is extremely slow, lasting from several years to decades. However, the presence of advanced lesions such as plaques or tumors shows significant invasive biological behavior, including the involvement of peripheral blood, lymph nodes, or visceral organs. To explore a biomarker that can predict the biological behavior transformation of MF, IL-13 is extremely important for the clinical management and treatment selection of MF as Th2-related cytokines, which can directly promote tumor proliferation and / or synergistic inhibition of tumor immune surveillance. The receptor IL-13R 偽 1 and IL-13R 偽 2 are one of the newly discovered members of the hematogenous receptor family, and have a relatively high affinity to IL-13, so it needs to be a specific and promising target for tumor gene therapy. Objective to detect and analyze the expression of IL-13 and its receptor in skin lesions of MF patients at different stages in order to provide a new marker and candidate molecular therapeutic target for the biological behavior transformation and progression of MF. Methods from January 2010 to March 2016, 34 cases of MF paraffin tissues confirmed by pathological examination, immunophenotype and / or T cell receptor gene rearrangement were collected and divided into stage 鈪，

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