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人白細(xì)胞介素24表達(dá)水平與食管癌進(jìn)程相關(guān)性的研究

發(fā)布時(shí)間:2018-06-05 11:40

  本文選題:IL-24 + 食管癌; 參考:《北京交通大學(xué)》2017年碩士論文


【摘要】:目的:人白細(xì)胞介素24(interleukin 24,IL-24)能夠在體內(nèi)外特異性抑制多種腫瘤細(xì)胞增殖,誘導(dǎo)其凋亡,對(duì)正常細(xì)胞沒(méi)有影響;同時(shí),可以抑制新生血管形成,刺激免疫系統(tǒng)對(duì)腫瘤發(fā)生反應(yīng),增加腫瘤細(xì)胞的放化療敏感性;并且,隨著黑色素瘤發(fā)生和發(fā)展,IL-24的表達(dá)水平顯著降低,腫瘤患者(肺腺癌、乳腺癌和結(jié)腸癌)癌組織中IL-24表達(dá)水平高則預(yù)后良好,提示IL-24可能是一個(gè)新的腫瘤預(yù)后標(biāo)志物。為了明確IL-24表達(dá)水平與食管癌進(jìn)程相關(guān)性,本文測(cè)定和分析了食管癌患者組織標(biāo)本和血液標(biāo)本中IL-24表達(dá)水平。方法:采用免疫組織化學(xué)(Immunohistochemical,IHC)方法檢測(cè)84位食管癌患者配對(duì)標(biāo)本(腫瘤組織,癌旁組織和正常組織)中IL-24表達(dá)水平,以及與IL-24 作用機(jī)制相關(guān)分子(如細(xì)胞增殖、細(xì)胞凋亡、細(xì)胞周期、新生血管形成、化療增敏、原癌基因、腫瘤干細(xì)胞、上皮間質(zhì)轉(zhuǎn)換、細(xì)胞自噬等)的表達(dá)水平。同時(shí)用酶聯(lián)免疫吸附測(cè)定(enzyme linked immunosorbent assay,ELISA)方法檢測(cè)了1940例血液標(biāo)本中的IL-24、人白細(xì)胞介素6(interleukin 6,IL-6)、人白細(xì)胞介素10(interleukin 10,IL-10)和腫瘤壞死因子 α(tumornecrosis factor α,TNF-α)的含量;以及13例食管癌患者血液標(biāo)本中IL-24的含量。結(jié)果:(1)在食管癌配對(duì)的組織標(biāo)本中IL-24表達(dá)水平存在差異,其中腫瘤組織中最高,正常組織中最低;(2)IL-24表達(dá)水平與84例食管癌患者年齡、性別、組織類(lèi)型、病變部位、病理分級(jí)、腫瘤分期(腫瘤大小和淋巴結(jié)轉(zhuǎn)移)和43例食管癌的分化程度等臨床特征,無(wú)統(tǒng)計(jì)學(xué)意義的相關(guān)性,但與69例食管鱗癌的腫瘤大小(p=0.09)和淋巴結(jié)轉(zhuǎn)移(p=0.06)負(fù)相關(guān);(3)食管癌的癌組織中IL-24表達(dá)水平與凋亡標(biāo)志分子半胱氨酸的天冬氨酸蛋白水解酶3(cysteinyl aspartate specific proteinase 3,Caspase3)正相關(guān),與 Fas 和 DNA 錯(cuò)配修復(fù)標(biāo)志分子 hMLH1(MutL homolog 1)負(fù)相關(guān),具有統(tǒng)計(jì)學(xué)意義。(4)血液標(biāo)本處理方式影響IL-24的檢測(cè)結(jié)果,同一位獻(xiàn)血者EDTA抗凝血中IL-24的檢出值最高,檸檬酸鈉抗凝血的最低。血液標(biāo)本在4℃存放15天對(duì)IL-24檢測(cè)結(jié)果影響不明顯。(5)血清中IL-24濃度與獻(xiàn)血者的年齡和血液生化指標(biāo)(血糖、血紅蛋白、總膽固醇、癌胚抗原、淋巴細(xì)胞絕對(duì)值、甲胎蛋白、白細(xì)胞、促甲狀腺激素、谷丙轉(zhuǎn)氨酶等)無(wú)關(guān)。(6)血液中IL-24表達(dá)水平與致炎因子IL-6和TNF-α表達(dá)水平正相關(guān),與抗炎因子IL-10表達(dá)水平負(fù)相關(guān),p值均小于0.05,具有統(tǒng)計(jì)學(xué)意義。結(jié)論:食管癌組織中IL-24蛋白表達(dá)水平遠(yuǎn)高于配對(duì)的癌旁組織和正常組織,且IL-24表達(dá)水平與食管鱗癌的腫瘤大小和淋巴結(jié)轉(zhuǎn)移數(shù)量負(fù)相關(guān),提示IL-24可能在食管鱗癌的發(fā)展進(jìn)程中發(fā)揮作用。
[Abstract]:Objective: human interleukin (24(interleukin) 24 IL-24 can specifically inhibit the proliferation of many tumor cells in vitro and in vivo, induce their apoptosis, and have no effect on normal cells, at the same time, they can inhibit angiogenesis and stimulate the immune system to respond to tumor. The expression of IL-24 was significantly decreased with the development of melanoma, and the higher expression of IL-24 in cancer tissues (lung adenocarcinoma, breast cancer and colon cancer) had a good prognosis. The results suggest that IL-24 may be a new prognostic marker. In order to determine the correlation between the expression of IL-24 and the progression of esophageal cancer, the expression of IL-24 in tissues and blood samples of patients with esophageal cancer was measured and analyzed. Methods: immunohistochemical method was used to detect the expression of IL-24 in 84 matched specimens of esophageal carcinoma (tumor tissues, adjacent tissues and normal tissues), as well as the molecules related to the mechanism of IL-24, such as cell proliferation and apoptosis. Cell cycle, neovascularization, chemosensitization, proto-oncogene, tumor stem cells, epithelial mesenchymal transformation, autophagy, etc. The contents of IL-24, IL-6, IL-6, IL-10 and TNF- 偽 in 1940 blood samples were also detected by enzyme linked immunosorbent assayanine Elisa. The levels of IL-24, IL-6, IL-10 and TNF- 偽) in 1940 blood samples were determined by Elisa. The serum levels of IL-24, IL-6, IL-10 and TNF- 偽 in 1940 blood samples were determined by Elisa. And the content of IL-24 in blood of 13 patients with esophageal carcinoma. Results there was significant difference in the expression of IL-24 in the matched tissues of esophageal carcinoma. The expression level of IL-24 was the highest in the tumor tissue and the lowest in the normal tissue. The expression level of IL-24 was the same as the age, sex, type of tissue, pathological grade and pathological grade of 84 patients with esophageal carcinoma. The clinical features of tumor staging (tumor size and lymph node metastasis) and the differentiation of 43 cases of esophageal carcinoma were not correlated with statistical significance. However, the expression of IL-24 was negatively correlated with tumor size (p0.09) and lymph node metastasis (p0.06) in 69 cases of esophageal squamous cell carcinoma. The expression of IL-24 was positively correlated with the apoptotic marker cysteine aspartate protein hydrolase 3(cysteinyl aspartate specific proteinase 3 (caspase3). It was negatively correlated with Fas and DNA mismatch repair marker molecule hMLH1(MutL homolog 1, and had statistical significance. 4) the treatment of blood samples affected the detection results of IL-24. In the same blood donor, the detection value of IL-24 was the highest in EDTA and the lowest in sodium citrate anticoagulant. Blood samples stored at 4 鈩,

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