本文選題：HMGB1 + 腫瘤相關(guān)巨噬細(xì)胞��； 參考：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：腫瘤微環(huán)境是一個(gè)由腫瘤細(xì)胞、基質(zhì)細(xì)胞、免疫細(xì)胞以及細(xì)胞因子等共同構(gòu)成的腫瘤局部復(fù)雜的炎性環(huán)境。大量研究已經(jīng)證實(shí)腫瘤微環(huán)境中大量的細(xì)胞因子以及免疫炎性反應(yīng),對(duì)腫瘤的發(fā)生、進(jìn)展等產(chǎn)生重要影響。HMGB1與腫瘤相關(guān)巨噬細(xì)胞作為腫瘤局部微環(huán)境的重要組成部分,對(duì)腫瘤的淋巴管生成以及后續(xù)的淋巴結(jié)轉(zhuǎn)移有重要作用。同時(shí),HMGB1作為外源性刺激因子,能作用于巨噬細(xì)胞進(jìn)一步發(fā)揮其細(xì)胞學(xué)效應(yīng)。該研究旨在探討二者在促進(jìn)腫瘤淋巴管生成方面有無相關(guān)性。 方法：(1)免疫組化(S-P法)分別檢測(cè)上皮性卵巢癌以及正常卵巢組織中HMGB1、腫瘤相關(guān)巨噬細(xì)胞(TAMs)及淋巴管密度(LVD)的表達(dá)。(2)用Spearman等級(jí)相關(guān)分析對(duì)上皮性卵巢癌患者HMGB1表達(dá)與LVD進(jìn)行相關(guān)性分析,用Pearson相關(guān)分析對(duì)上皮性卵巢癌患者CD68陽性腫瘤相關(guān)巨噬細(xì)胞計(jì)數(shù)與LVD進(jìn)行相關(guān)性分析。(3)MACS技術(shù)獲取上皮性卵巢癌患者腹水中TAMs,設(shè)立對(duì)照組與實(shí)驗(yàn)組,對(duì)照組為未處理的LECs；實(shí)驗(yàn)組：分別用rHMGB1(2μg/ml)、CD14陽性腫瘤相關(guān)巨噬細(xì)胞培養(yǎng)上清、rHMGB1(2μg/ml)預(yù)處理的CD14陽性腫瘤相關(guān)巨噬細(xì)胞培養(yǎng)上清以及rVEGF-C(5ng/ml)處理的LECs作為實(shí)驗(yàn)組,通過CCK-8實(shí)驗(yàn)、細(xì)胞遷移實(shí)驗(yàn)、成管實(shí)驗(yàn)觀察各組之間在淋巴管內(nèi)皮細(xì)胞增殖、遷移、成管能力之間的差異。 結(jié)果：(1)免疫組化結(jié)果顯示：上皮性卵巢癌組織中HMGB1的表達(dá)和腫瘤相關(guān)巨噬細(xì)胞的浸潤(rùn)明顯高于正常卵巢組織,兩組之間的差異有顯著統(tǒng)計(jì)學(xué)意義,且與淋巴結(jié)轉(zhuǎn)移相關(guān)。(2)用Spearman等級(jí)相關(guān)分析對(duì)上皮性卵巢癌患者HMGB1表達(dá)與LVD進(jìn)行相關(guān)性分析,可見上皮性卵巢癌患者中HMGB1表達(dá)與LVD成正相關(guān)(r=0.491,P0.001)。用Pearson目關(guān)分析對(duì)上皮性卵巢癌患者腫瘤相關(guān)巨噬細(xì)胞與LVD進(jìn)行相關(guān)性分析,提示上皮性卵巢癌患者腫瘤相關(guān)巨噬細(xì)胞計(jì)數(shù)與LVD成明顯正相關(guān)(R2=0.242,P0.001)。(3)體外實(shí)驗(yàn)結(jié)果提示：HMGB1與腫瘤相關(guān)巨噬細(xì)胞均可以促進(jìn)淋巴管內(nèi)皮細(xì)胞增殖、遷移、成管,然而,當(dāng)二者相互作用后,這種促進(jìn)淋巴管內(nèi)皮細(xì)胞增殖、遷移、成管的能力大大增強(qiáng)。 結(jié)論：上皮性卵巢癌中組織中HMGB1的表達(dá)和腫瘤相關(guān)巨噬細(xì)胞的浸潤(rùn)明顯高于正常卵巢組織,且與腫瘤淋巴結(jié)轉(zhuǎn)移密切相關(guān)。HMGB1與腫瘤相關(guān)巨噬細(xì)胞均可以促進(jìn)淋巴管內(nèi)皮細(xì)胞增殖、遷移、成管,然而,當(dāng)二者相互作用后,這種促進(jìn)淋巴管內(nèi)皮細(xì)胞增殖、遷移、成管的能力大大增強(qiáng),這將為抗卵巢癌淋巴管生成的靶向治療提供理論依據(jù)。
[Abstract]:Objective: tumor microenvironment is a complex inflammatory environment composed of tumor cells, stromal cells, immune cells and cytokines. A large number of studies have confirmed that a large number of cytokines and immune inflammatory reactions in tumor microenvironment have important effects on tumor occurrence and progression. HMGB1 and tumor-associated macrophages are important components of tumor local microenvironment. It plays an important role in lymphangiogenesis and subsequent lymph node metastasis. At the same time, HMGB1, as an exogenous stimulant factor, can further exert its cytological effect on macrophages. The aim of this study was to investigate whether there is a correlation between the two in promoting lymphangiogenesis in tumors. Methods: (1) Immunohistochemistry (S-P method) was used to detect the expression of HMGB1, tumor associated macrophages (TAMs) and lymphatic vessel density (LVD) in epithelial ovarian carcinoma and normal ovarian tissues, respectively. (2) Spearman grade correlation analysis was used to detect HMGB1 expression in epithelial ovarian cancer patients. Da and LVD were analyzed. Pearson correlation analysis was used to analyze the correlation between CD68 positive tumor associated macrophage count and LVD in epithelial ovarian cancer patients. (3) Macs was used to obtain TAMsin ascites of patients with epithelial ovarian cancer. The control group and experimental group were set up and the control group was untreated LECs. Experimental group: LECs pretreated with rHMGB1 (2 渭 g/ml) tumor associated macrophage culture supernatant and rVEGF-C (5ng/ml) treated with rHMGB1 (2 渭 g/ml) were used as experimental group. The proliferation, migration and ability of lymphatic endothelial cells were observed. Results: (1) Immunohistochemical results showed that the expression of HMGB1 and the infiltration of tumor associated macrophages in epithelial ovarian carcinoma were significantly higher than those in normal ovarian tissues, and the difference between the two groups was statistically significant. (2) the expression of HMGB1 in epithelial ovarian cancer was correlated with LVD by Spearman rank correlation analysis. The positive correlation between HMGB1 expression and LVD was found in epithelial ovarian cancer patients (r 0.491p0.001). The correlation between tumor associated macrophages and LVD in patients with epithelial ovarian cancer was analyzed by Pearson muzzle analysis. These results suggest that the number of tumor-associated macrophages in epithelial ovarian cancer patients is positively correlated with LVD (R2O0.242P0.001). (3). The results of in vitro experiments indicate that both the tumor associated macrophages and the tumor associated macrophages can promote the proliferation, migration and angiogenesis of lymphatic endothelial cells. When the two interact, the ability to promote the proliferation, migration and angiogenesis of lymphatic endothelial cells is greatly enhanced. Conclusion: the expression of HMGB1 and the infiltration of tumor-associated macrophages in epithelial ovarian carcinoma are significantly higher than those in normal ovarian tissues. HMGB1 and tumor-associated macrophages can promote the proliferation, migration and angiogenesis of lymphatic endothelial cells. However, when the two interactions, this can promote the proliferation and migration of lymphatic endothelial cells. The ability of angiogenesis is greatly enhanced, which will provide a theoretical basis for targeted therapy against lymphangiogenesis of ovarian cancer.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.31

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 杜曉琴;付欣;郝權(quán);;HMGB-1基因及其受體RAGE在宮頸鱗癌中的表達(dá)及臨床意義[J];天津醫(yī)科大學(xué)學(xué)報(bào);2008年01期

2 Vlp K.;Brezniceanu M.-L.;Bsser S.;M. Zrnig;劉麗娜;;人結(jié)腸癌HMGB1基因表達(dá)增加與抗凋亡蛋白c-IAP2水平增高的相關(guān)性[J];世界核心醫(yī)學(xué)期刊文摘(胃腸病學(xué)分冊(cè));2006年Z1期

，

本文編號(hào)：2113287