【作者】 曹赣；

【导师】 匡玉庭；

【作者基本信息】 苏州大学 ， 普外科， 2008， 硕士

【摘要】 多年来,化疗和手术一直都是胃癌治疗的两个主要手段,取得了一定的疗效,但由于胃癌细胞的耐药以及胃癌的侵袭转移特性,使得胃癌的临床疗效很难有大的突破。多药耐药(multidrug resistance MDR)的产生是肿瘤化疗失败的主要原因。DNA拓扑异构酶Ⅱ(DNA TopoⅡ)既是某些细胞毒药物作用靶点,又是MDR的重要靶酶,介导多种化疗药物的MDR。CD44是一种存在于细胞表面的跨膜糖蛋白,其拼接变异体CD44v6能介导淋巴细胞归巢并参与细胞间的黏附过程,与许多肿瘤的侵袭转移密切相关。有关DNATopoⅡ与肿瘤耐药的关系方面已有深入的研究,文献较多。但在肿瘤耐药和肿瘤侵袭转移相关性方面,国内外的文献报道较少。本文着点于联合研究DNA TopoⅡ和CD44V6在胃癌组织中的表达并分析二者的相关性,以探讨其作用机制。目的探讨DNA TopoⅡ和CD44v6在胃癌组织中的表达及其临床意义,以及二者之间的相关性,研究胃癌肿瘤耐药和胃癌肿瘤侵袭转移之间的关系。方法选择86例胃癌组织标本,分别取原发癌灶、及正常胃黏膜(距癌灶4cm以外)组织各2枚,采用免疫组织化学方法SP法检测DNA TopoⅡ和CD44v6的表达。卡方检验和SAS软件包进行统计学分析结果DNA TopoⅡ和CD44v6在胃癌中阳性表达率分别为40.69%和50%,胃癌组织中DNA TopoⅡ的高表达与肿瘤的淋巴结转移和分化程度密切相关(P＜0.05),与肿瘤浸润深度不相关。胃癌组织中CD44v6的高表达与肿瘤的淋巴结转移和浸润深度密切相关(P＜0.05),与肿瘤的分化程度不相关。CD44v6在DNA TopoⅡ表达阳性的胃癌组织中的阳性率明显高于DNATopoⅡ表达阴性者(P＜0.05)。结论DNATopoⅡ和CD44v6是胃癌发生发展的重要因素。DNATopoⅡ可作为评价胃癌化疗耐药的指标,与胃癌的分化和转移有密切相关;CD44v6可作为胃癌转移潜能衡量的指标。肿瘤化疗耐药和肿瘤转移密切相关,联合检测胃癌组织中DNATopoⅡ和CD44V6的表达可能反映胃癌的临床生物学行为,可以指导围手术期化疗和手术治疗,选择敏感的化疗药物可能会抑制甚至逆转肿瘤的转移潜能。更多还原

【Abstract】 Chemotherapy and surgical operation have been two main means and obtained obvious effect in gastric carcinoma treatments.The clinical curative effect of gastric carcinoma is not satisfactory because of chemotherapeutic agents resistance and invasion of tumor cells.Multidrug resistance(MDR)is one of the main reasons which causes chemotherapy failure,DNA topoisomeraseⅡ(TopoⅡ)is the target point for some cytotoxic drugs,and is also the important target enzyme of MDR,which mediate the MDR of many chemotherapeutics.CD44 is a kind of transmembrane glycoprotein existing in cell surface.CD44v6 is a splicing variant of CD44 mediating lymphocyte’s homing, participating in the adhesion action among cells,which play a important role in tumor transference and invasion.Demonstration about the relationship between DNA TopoⅡand MDR could be seen in many articles,but we have not seen few reports about relationship in MDR,metastasis and invasion for gastric carcinoma.The aim of tiffs study is to examine the expression of DNA TopoⅡand CD44V6 and their relationship in gastric carcinoma.Objective:To examine the expression and significance of DNA TopoⅡand CD44v6 and their relationship with invasion and metastasis for gastric carcinoma.Methods:Immunohistochemistry SP method was used to determine the expression of DNA TopoⅡand CD44v6 in carcinoma mucosa and normal mucosa(4cm away from carcinoma edge)in 86 tumor samples from the patients with gastric carcinoma.Date was analyzed by chi-squie test.Results:The positive expression rates of DNA TopoⅡand CD44v6 in gastric carcinoma were 40.69%and 50%,respectively.The higher expression ofDNA TopoⅡwas significantly associated with lymph nodes metastasis and differentiation degree(P＜0.05), and had no correlation to infiltration depth(P＞0.05).The higher expression of CD44v6 was significantly associated with lymph nodes metastasis and infiltration depth(P＜0.05), andhad no correlation to differentiation degree(P＞0.05).The positive expression rates of CD44v6 in DNA TopoⅡpositive expression group were remarkably higher than that in TopoⅡnegative expression group.Conclusion:Both DNA TopoⅡand CD44v6 play important role in gastric carcinoma development and progression.DNA TopoⅡexpression may be a useful predictor of MDR, and is relevant to differentiation degree and metastasis in gastric carcinoma.The expression of CD44v6 may be a useful marker for predicting the metastasis potency.MDR has significantly correlation to infiltration depth in gastric carcinoma.Detecting expression of DNA TopoⅡand CD44v6 might reflect the clinical biology behavior and guide the chemotherapy and surgery for gastric carcinoma.Sensitive chemotherapy medicine may inhibit or reverse the metastasis potency for gastric carcinoma.更多还原