DNA TopoⅡ和CD44v6在胃癌组织中的表达及其相关性研究
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。
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.
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。
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.
引文
(1)祁向东,郝波,张国新,等.CD44v6在胃癌组织中的表达及意义,江苏医药,2006,32(9):857-858.
(2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
(3)Shabbits JA.et al Molecular and pharmacological strategies to overcome multidrug resistance,Expert Rev Anticancer Ther.2001 Dec;1(4):585-594
(4)张春军,孙晓波,金锋,等.多药耐药基因Topo Ⅱ αmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
(5)Kim R,Ohi Y et al.Expression and relationship between topoisomerase Ⅰ and Ⅱalpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(6)Ito K,Sasano H.et al.Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-294
(7)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
(8)鞠芳,张婷,杜国威,等.P-gp,GST-π和TopoⅡ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
(9)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
(10)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
(11)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(1)徐惠绵;胃肠癌基础研究的现状与展望,中华实验外科杂志,2000,17(4):296
(2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
(3)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(4)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(5)Bakshi RP,et al.Functional and regulatory characteristics of eukaryotic type ⅡDNA topoisomerase.Crit Rev Biochem Mol Biol.2001;36(1):31-37
(6)Liu D.et al.Topoisomerase Ⅱalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.Cancer.2002 Apr 15;94(8):2239-2247
(7)Yabuki N,et al.Immunohistochemical study of DNA topoisomerase Ⅱ in human gastric disorders.Am J Pathol.1996 Sep;149(3):1997-1007
(8)Koshiyama M,et al.Correlation between Topo Ⅱ alpha expression and chemosensitivity testing for Topo Ⅱ-targeting drugs in gynaecological carcinomas.Anticancer Res.2001 Mar-Apr;21(2A):905-910
(9)Coleman LW.et al.Immunohistochemical staining for DNA topoisomerase Ⅰ,DNA topoisomerase Ⅱ-alpha and p53 in gastric carcinomas.Anticancer Res.2001Mar-Apr;21(2A):1167-1172
(10)Kim R,Ohi Y.et al,Expression and relationship between topoisomerase Ⅰ and Ⅱ alpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(11)Ito K,Sasano H.et al,Immunohistochemical Study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-94
(12)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、TopoⅡ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
(13)荆雪宁,张玲,等,CD44与肿瘤的免疫逃逸,国外医学.肿瘤学分册,2004,31(3):186-190.
(14)Weber GF.et al.Absence of the CD44 gone prevents sarcoma metastasis.Cancer Res.2002 Apr 15;62(8):2281-2286.
(15)Chen JQ,Zhan WH.et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(16)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
(17)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
(18)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5and 6 in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(19)陈建利,张琴,丰有吉。肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392
(20)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
1)祁向东,郝波,张国新,等.CD44v6在胃癌组织中的表达及意义,江苏医药,2006,32(9):857-858.
2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
3)Shabbits JA.et al Molecular and pharmacological strategies to overcome multidrug resistance,Expert Rev Anticancer Ther.2001 Dec;1(4):585-594
4)张春军,孙晓波,金锋,等.多药耐药基因TopoⅡαmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
5)Ito K,Sasano H.et al.Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱin human endometrium,Mod Pathol.1997 Apr;10(4):289-294
6)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
7)鞠芳,张婷,杜国威,等.P-gp,GST-π和TopoⅡ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
8)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
9)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
10)徐惠绵;胃肠癌基础研究的现状与展望,中华实验外科杂志,2000,17(4):296
11)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
12)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
13)Bakshi RP,et al.Functional and regulatory characteristics of eukaryotic type Ⅱ DNA topoisomerase.Crit Rev B iochem Mol Biol.2001;36(1):31-37
14)Liu D.et al.Topoisomerase Ⅱalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.Cancer.2002 Apr 15;94(8):2239-2247
15)Yabuki N,et al.Immunohistochemical study of DNA topoisomerase Ⅱ in human gastric disorders.Am J Pathol.1996 Sep;149(3):1997-1007
16)Koshiyama M,et al.Correlation between Topo Ⅱ alpha expression and chemosensitivity testing for Topo Ⅱ-targeting drugs in gynaecological carcinomas.Anticancer Res.2001 Mar-Apr;21(2A):905-910
17)Coleman LW.et al.Immunohistochemical staining for DNA topoisomerase Ⅰ,DNA topoisomerase Ⅱ-alpha and p53 in gastric carcinomas.Anticancer Res.2001Mar-Apr;21(2A):1167-1172
18)Kim R,Ohi Y.et al,Expression and relationship between topoisomerase Ⅰ and Ⅱalpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
19)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、TopoⅡ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
20)荆雪宁,张玲,等,CD44与肿瘤的免疫逃逸,国外医学.肿瘤学分册,2004,31(3):186-190.
21)Weber GF.et al.Absence of the CD44 gene prevents sarcoma metastasis.Cancer Res.2002 Apr 15;62(8):2281-2286.
22)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
23)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
24)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5 and 6in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(1)鞠芳,张婷,杜国威,等.P-gp,GST-π和Topo Ⅱ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
(2)张春军,孙晓波,金锋,等.多药耐药基因Topo Ⅱ αmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
(3)Kim R,Ohi Y 等,Expression and relationship between topoisomerase Ⅰ and Ⅱ alpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(4)Ito K,Sasano H 等,Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-94
(5)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
(6)Nakopoulou L,Lazads AC.et al.DNA topoisomerase Ⅱ-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer.,Pathobiology.2000May-Jun;68(3):137-243
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(9)张声,陈林莺,李莉,等.拓扑异梅酶Ⅱ在胃癌中的表达,福建医科大学学报,2000,34(2):132-136.
(10)陈晓耕,施作霖,王清水,等.DNA拓扑异构酶在胃癌中的表达及其与预后关系探讨,福建医药杂志,1999,21(3):08-10.
(11)徐守余,杨道华,邱承敏,等.P-糖蛋白、谷胱苷肽-S-转移酶和DNA拓扑异构酶Ⅱ在胃癌中的表达及意义,实用肿瘤学杂志,2004,18(3):213-216.
(12)Oudard S,Levalois C,et al.Expression of genes involved in chemoresistance,proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome,Anticancer Res.2002 Jan-Feb;22(1A):121-128
(13)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
(14)祁向东,郝波,张国新,等.CD44v6在胃癌组织中的表达及意义,江苏医药,2006,32(9):857-858.
(15)范开席,郭其森,胡伟,等.CD44V6和nm23-H1在胃癌中的表达及预后 价值,实用临床医学,2005,6(10):1-5.
(16)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(17)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
(18)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5and 6 in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(19)赵增强;余佩武,赵永亮,等.胃癌中RhoC和CD44v6及ICAM-1的表达及其相关性的初步研究,中华胃肠外科杂志,2005,8(4):352-356.
(20)孙喜文,申宝忠,石美森,等.CD44v6基因表达与胃癌危险因素的关系,世界华人消化杂志,2002,10(10):1129-1132。
(21)叶辉,王伟,张兴林,等.CD44V6在胃癌组织中的表达及其临床意义,安徽医药,2005,9(7):532-534.
(22)费建东,薛军,张林西,等.进展期胃癌HSP900α、CD44v6表达与其临床生物学行为关系的研究,世界华人消化杂志,2005,13(6):793-795.
(23)Joo M,Lee HK.et al Expression of E-cadherin,beta-catenin,CD44s and CD44v6in gastric adenocarcinoma:relationship with lymph node metastasis.Anticancer Res.2003 Mar-Apr;23(2B):1581-1588
(24)Vizoso FJ,Fernandez JC.et al.Expression and clinical significance of CD44V5and CD44V6 in resectable colorectal cancer.J Cancer Res Clin Oncol.2004Nov;130(11):679-686.Epub 2004 Aug 6.
(25)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
(26)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(27)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44 interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
(28)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、Topo Ⅱ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
(2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
(3)Shabbits JA.et al Molecular and pharmacological strategies to overcome multidrug resistance,Expert Rev Anticancer Ther.2001 Dec;1(4):585-594
(4)张春军,孙晓波,金锋,等.多药耐药基因Topo Ⅱ αmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
(5)Kim R,Ohi Y et al.Expression and relationship between topoisomerase Ⅰ and Ⅱalpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(6)Ito K,Sasano H.et al.Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-294
(7)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
(8)鞠芳,张婷,杜国威,等.P-gp,GST-π和TopoⅡ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
(9)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
(10)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
(11)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(1)徐惠绵;胃肠癌基础研究的现状与展望,中华实验外科杂志,2000,17(4):296
(2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
(3)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(4)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(5)Bakshi RP,et al.Functional and regulatory characteristics of eukaryotic type ⅡDNA topoisomerase.Crit Rev Biochem Mol Biol.2001;36(1):31-37
(6)Liu D.et al.Topoisomerase Ⅱalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.Cancer.2002 Apr 15;94(8):2239-2247
(7)Yabuki N,et al.Immunohistochemical study of DNA topoisomerase Ⅱ in human gastric disorders.Am J Pathol.1996 Sep;149(3):1997-1007
(8)Koshiyama M,et al.Correlation between Topo Ⅱ alpha expression and chemosensitivity testing for Topo Ⅱ-targeting drugs in gynaecological carcinomas.Anticancer Res.2001 Mar-Apr;21(2A):905-910
(9)Coleman LW.et al.Immunohistochemical staining for DNA topoisomerase Ⅰ,DNA topoisomerase Ⅱ-alpha and p53 in gastric carcinomas.Anticancer Res.2001Mar-Apr;21(2A):1167-1172
(10)Kim R,Ohi Y.et al,Expression and relationship between topoisomerase Ⅰ and Ⅱ alpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(11)Ito K,Sasano H.et al,Immunohistochemical Study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-94
(12)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、TopoⅡ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
(13)荆雪宁,张玲,等,CD44与肿瘤的免疫逃逸,国外医学.肿瘤学分册,2004,31(3):186-190.
(14)Weber GF.et al.Absence of the CD44 gone prevents sarcoma metastasis.Cancer Res.2002 Apr 15;62(8):2281-2286.
(15)Chen JQ,Zhan WH.et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(16)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
(17)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
(18)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5and 6 in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(19)陈建利,张琴,丰有吉。肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392
(20)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
1)祁向东,郝波,张国新,等.CD44v6在胃癌组织中的表达及意义,江苏医药,2006,32(9):857-858.
2)李海,郑春宁,薛强,等.胃癌组织中的肺耐药蛋白、P糖蛋白、谷胱甘肽-S-转移酶以及拓扑异构酶Ⅱ的表达及意义,中华实验外科杂志,2005,22(1):58-60.
3)Shabbits JA.et al Molecular and pharmacological strategies to overcome multidrug resistance,Expert Rev Anticancer Ther.2001 Dec;1(4):585-594
4)张春军,孙晓波,金锋,等.多药耐药基因TopoⅡαmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
5)Ito K,Sasano H.et al.Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱin human endometrium,Mod Pathol.1997 Apr;10(4):289-294
6)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
7)鞠芳,张婷,杜国威,等.P-gp,GST-π和TopoⅡ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
8)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
9)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
10)徐惠绵;胃肠癌基础研究的现状与展望,中华实验外科杂志,2000,17(4):296
11)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
12)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
13)Bakshi RP,et al.Functional and regulatory characteristics of eukaryotic type Ⅱ DNA topoisomerase.Crit Rev B iochem Mol Biol.2001;36(1):31-37
14)Liu D.et al.Topoisomerase Ⅱalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.Cancer.2002 Apr 15;94(8):2239-2247
15)Yabuki N,et al.Immunohistochemical study of DNA topoisomerase Ⅱ in human gastric disorders.Am J Pathol.1996 Sep;149(3):1997-1007
16)Koshiyama M,et al.Correlation between Topo Ⅱ alpha expression and chemosensitivity testing for Topo Ⅱ-targeting drugs in gynaecological carcinomas.Anticancer Res.2001 Mar-Apr;21(2A):905-910
17)Coleman LW.et al.Immunohistochemical staining for DNA topoisomerase Ⅰ,DNA topoisomerase Ⅱ-alpha and p53 in gastric carcinomas.Anticancer Res.2001Mar-Apr;21(2A):1167-1172
18)Kim R,Ohi Y.et al,Expression and relationship between topoisomerase Ⅰ and Ⅱalpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
19)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、TopoⅡ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
20)荆雪宁,张玲,等,CD44与肿瘤的免疫逃逸,国外医学.肿瘤学分册,2004,31(3):186-190.
21)Weber GF.et al.Absence of the CD44 gene prevents sarcoma metastasis.Cancer Res.2002 Apr 15;62(8):2281-2286.
22)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
23)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
24)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5 and 6in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(1)鞠芳,张婷,杜国威,等.P-gp,GST-π和Topo Ⅱ在胃癌中的表达及临床意义,潍坊医学院学报,2007,29(2):155-157.
(2)张春军,孙晓波,金锋,等.多药耐药基因Topo Ⅱ αmRNA在胃癌及其相邻正常组织中表达,中国医科大学学报,2003,32(4):334-335
(3)Kim R,Ohi Y 等,Expression and relationship between topoisomerase Ⅰ and Ⅱ alpha genes in tumor and normal tissues in esophageal,gastric and colon cancers.Anticancer Res.1999 Nov-Dec;19(6B):5393-5398.
(4)Ito K,Sasano H 等,Immunohistochemical study of Ki-67 and DNA topoisomerase Ⅱ in human endometrium,Mod Pathol.1997 Apr;10(4):289-94
(5)吴波,闫伟,方刚,等.DNA拓扑异构酶Ⅱ在增殖细胞中的表达及其意义,医学研究生学报,2004,17(3):240-246.
(6)Nakopoulou L,Lazads AC.et al.DNA topoisomerase Ⅱ-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer.,Pathobiology.2000May-Jun;68(3):137-243
(7)于冬青,易永芬.MRP、GST-π、Topo Ⅱ α和LRP在胃癌组织中的表达及意义,癌症,2003,22(5):496-499
(8)Qin F,Qin X.et al.Expression and.significance of P-gtycoprotein,glutathione S-transferase-pi and Topoisomerase Ⅱ in gastric carcinomas,Ai Zheng.2002Feb;21(2):167-170
(9)张声,陈林莺,李莉,等.拓扑异梅酶Ⅱ在胃癌中的表达,福建医科大学学报,2000,34(2):132-136.
(10)陈晓耕,施作霖,王清水,等.DNA拓扑异构酶在胃癌中的表达及其与预后关系探讨,福建医药杂志,1999,21(3):08-10.
(11)徐守余,杨道华,邱承敏,等.P-糖蛋白、谷胱苷肽-S-转移酶和DNA拓扑异构酶Ⅱ在胃癌中的表达及意义,实用肿瘤学杂志,2004,18(3):213-216.
(12)Oudard S,Levalois C,et al.Expression of genes involved in chemoresistance,proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome,Anticancer Res.2002 Jan-Feb;22(1A):121-128
(13)张俊华,眭昕.CD44V6与PCNA在胃癌中的表达及其相互关系,交通医学,2007,21(2):123-126.
(14)祁向东,郝波,张国新,等.CD44v6在胃癌组织中的表达及意义,江苏医药,2006,32(9):857-858.
(15)范开席,郭其森,胡伟,等.CD44V6和nm23-H1在胃癌中的表达及预后 价值,实用临床医学,2005,6(10):1-5.
(16)Chen JQ,Zhan WH,et al.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.World J Gastroenterol.2004 Mar 15;10(6):776-782
(17)Washington K,Gottfried MR,et al Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas,Hum Pathol.1994 Oct;25(10):1043-1049
(18)Mirecka J,Marx D.et al,Immunohistochemical localization of CD44 variants 5and 6 in human gastric mucosa and gastric cancer.Anticancer Res.1995Jul-Aug;15(4):1459-1465
(19)赵增强;余佩武,赵永亮,等.胃癌中RhoC和CD44v6及ICAM-1的表达及其相关性的初步研究,中华胃肠外科杂志,2005,8(4):352-356.
(20)孙喜文,申宝忠,石美森,等.CD44v6基因表达与胃癌危险因素的关系,世界华人消化杂志,2002,10(10):1129-1132。
(21)叶辉,王伟,张兴林,等.CD44V6在胃癌组织中的表达及其临床意义,安徽医药,2005,9(7):532-534.
(22)费建东,薛军,张林西,等.进展期胃癌HSP900α、CD44v6表达与其临床生物学行为关系的研究,世界华人消化杂志,2005,13(6):793-795.
(23)Joo M,Lee HK.et al Expression of E-cadherin,beta-catenin,CD44s and CD44v6in gastric adenocarcinoma:relationship with lymph node metastasis.Anticancer Res.2003 Mar-Apr;23(2B):1581-1588
(24)Vizoso FJ,Fernandez JC.et al.Expression and clinical significance of CD44V5and CD44V6 in resectable colorectal cancer.J Cancer Res Clin Oncol.2004Nov;130(11):679-686.Epub 2004 Aug 6.
(25)陈建利,张琴,丰有吉.肿瘤粘附分子表达和卵巢癌化疗耐药的关系,国外医学.肿瘤学分册,2001,28(5):389-392.
(26)梅静,陈古福.PgP和CD44V6在胃癌中的表达及其临床意义,皖南医学院学报,2007,26(1):46-49.
(27)Wang SJ,Peyrollier K,Bourguignon LY.The influence of hyaluronan-CD44 interaction on topoisomerase Ⅱ activity and etoposide cytotoxicity in head and neck cancer.Arch Otolaryngol Head Neck Surg.2007 Mar;133(3):281-288.
(28)王希泽,宋福林,张雪峰,等.多药耐药基因产物P-gp、Topo Ⅱ在胃癌组织中的表达及意义,山东医药,2003,43(22)24-26.
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