人胃癌细胞中热休克蛋白（HSP）gp96和nm23表达的生物学意义及相关性研究
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摘要
目的:
通过检测慢性胃炎、消化性溃疡及胃癌组织中热休克蛋白gp96和nm23的表达,探讨它们在胃癌的发生发展及转移中作用和可能的分子机制,为胃癌的早期诊断、治疗方案制定、预后判断和肿瘤的分子治疗等提供理论基础。
方法:
应用免疫组织化学的方法检测慢性胃炎、消化性溃疡及胃癌组织中热休克蛋白gp96和nm23的表达情况,并分析它们与各临床病理参数之间的关系,应用SPSS11.5统计软件包进行卡方(x~2)数据处理。
结果:
1、试验组40例胃癌组织中HSPgp96和nm23的表达阳性率分别为67.5%和37.5%。HSPgp96的阳性率试验组显著高于对照组(慢性胃炎35%;消化性溃疡40%),且其差异性具有统计学意义(x~2 =5.74,P<0.05;x~2 =4.15, P<0.05);nm23的阳性率试验组明显低于对照着(慢性胃炎70%;消化性溃疡75%),且其差异性具有统计学意义(x~2 =5.64, P<0.05;x~2 =7.5,P<0.05)。
2、不同临床病理分期的胃癌组织中HSPgp96的表达阳性率不同:低分化组(72.7%)显著高于中、高分化组(38.9%),且其差异性具有统计学意义(x~2 =4.639,P<0.05);有淋巴结转移组(69.6%)显著高于无淋巴结转移组(29.4%),其差异性具有统计学意义(x~2 =6.32,P<0.05);TNM分型中III—IVI组(70.8%)显著高于I—II组(37.5%),其差异性具有统计学意义(x~2 =4.365,P<0.05)。大体形态中局限型(57.9%)与浸润型(57.1%)的差异性无统计学意义(x~2 =0.0023,P>0.05);侵犯深度中mps0(57%)与mps1-3(61.5%)的差异性无统计学意义(x~2 =0.0732, P>0.05)。
3、不同临床病理分期的胃癌组织中nm23的表达阳性率不同:低分化组(36.4%)显著低于中、高分化组(72.2%),且其差异性具有统计学意义(x~2 =5.1045,P<0.05);有淋巴结转移组(34.8%)显著低于无淋巴结转移组(70.6%),其差异性具有统计学意义(x~2 =5.013,P<0.05);TNM分型中Ⅲ—Ⅳ组(41.7%)显著低于I—II组(75%),其差异性具有统计学意义(x~2 =4.309,P<0.05)。大体形态中局限型(42.1%)与浸润型(42.9%)的差异性无统计学意义(x~2 =0.0023,P>0.05);侵犯深度中mps0(64.3%)与mps1-3(57.7%)的差异性无统计学意义(x~2 =0.1648,P>0.05)。
结论:
1、胃癌组织细胞中热休克蛋白gp96表达明显高于慢性胃炎及消化性溃疡,这提示了热休克蛋白gp96参与胃癌的发生。而在低分化胃癌的组织中的表达明显高于中高分化胃癌;有淋巴结转移的胃癌组织中的表达明显高于无淋巴结转移者;TNM分型中III+IV组织中的表达明显高于I+II型,说明了它与肿瘤的浸润转移密切相关;而不同大体形态及侵犯深度中,热休克蛋白gp96表达存在差异,这也从另一个侧面反应了热休克蛋白gp96在肿瘤大体形态及侵犯深度中的作用机制可能不同。2、胃癌组织细胞中nm23表达明显低于慢性胃炎及消化性溃疡,这提示了nm23与胃癌的形成有关。而在低分化胃癌的组织中的表达明显低于中高分化胃癌;有淋巴结转移的胃癌组织中的表达明显低于无淋巴结转移者;TNM分型中III+IV组织中的表达明显低于I+II型,说明了它与肿瘤的浸润转移密切相关;而不同大体形态及侵犯深度中,nm23表达存在差异,这也从另一个侧面反应了nm23在肿瘤大体形态及侵犯深度中的作用机制可能不同。
3、在胃癌的形成中,与热休克蛋白gp96表达呈正相关,而与nm23的表达呈负相关;在胃癌不同的临床病理分期中,热休克蛋白gp96与分化程度、淋巴结转移,TNM分型表达呈正相关;而nm23与之相反。试验表明热休克蛋白gp96及nm23在胃癌的形成和浸润转移中存在着协同作用。因而热休克蛋白gp96及nm23可作为胃癌的早期诊断、判断肿瘤预后的指标检测,其表达强度的高低有望成为指导临床治疗的一个手段。
Objective:
To make clear the roles which HSPgp96 and nm23 played in the occurrence、development、metastasis of chronic gastritis、peptic ulcer、gastric cancer and probable molecular mechanism of them,we intended to detect the expression of them and analyzed the relationship among them.we hope to supply a theoretical evidence for early diagnosis、cure a project、judgment of prognosis and tumor therapy.
Methods:
we applied SP immunohistochemical method to detect HSPgp96 and nm23 protein expressions and analyzed theirs relationship with each other in gastric cancer containing chronic gastritis、peptic ulcer.All date were processed by SPSS 11.5 analysis software to progress Chi-square test.
Results:
1、HSPgp96 and nm23 proteins were respectively detected in 67.5% and 37.5% of all 40 gastric cancer. HSPgp96 of testing group was higher than those of control group(chronic gastritis 35%、peptic ulcer 40%),and the differences were statistically significant(p<0.05). nm23 of testing group was less than those of control group(chronic gastritis 70%、peptic ulcer 75%),and the differences were statistically significant(p<0.05).
2、The expressions of HSPgp96 in different clinical pathology stages of gastric cancer were various: lowgrade(72.7%)>high-middlegrade(38.9%), the differences were statistically significant(x~2=4.639,p<0.05).With lymph node metastasis(69.9%)> Without lymph node metastasis(29.4%), the differences were statistically significant(x~2=6.32,p<0.05).In the TNM cent type,III+IV(70.8%)>I+II(37.5%), the differences were statistically significant(x~2=4.365,p<0.05). The differences between limited type(57.9%) and invaded type(57.1%)in the body form were not statistically significant(x~2=0.0023,p>0.05). The differences between MPSo(57%) and MPS 1-3(61.5%) in the invasion depth were not statistically significant (x~2=0.0732, p>0.05).
3、The expressions of nm23 in different clinical pathology stages of gastric cancer were various: lowgrade(36.4%)< high-middlegrade(72.2%), the differences were statistically significant(x~2=5.1045, p<0.05). With lymph node metastasis (34.8%)< Without lymph node metastasis(70.6%), the differences were statistically significant(x~2=5.013, p<0.05). In the TNM cent type,III+IV(41.7%)< I+II(75%), the differences were statistically significant(x~2=4.309, p<0.05). The differences between limited type(42.1%) and invaded type(42.9%) in the body form were not statistically significant(x~2=0.0023,p>0.05). The differences between MPSo(64.3%) and MPS1-3(57.7%) in the invasion depth were not statistically significant (x~2=0.1648, p>0.05).
Conclusion:
1、The expression of HSPgp96 was much higher in gastric cancer samples than in chronic gastritis samples or in peptic ulcer samples,which suggested it involved in carcinogenesis of human gastric cancer.while we detected lowgrade gastric cancer >high-middlegrade gastric cancer ; gastric cancer with lymph node metastasis> without lymph node metastasis; In the TNM cent type,III+IV>I+II, which proved HSPgp96 had a relationship with metastasis function in gastric cancer.There were some differences about expression of HSPgp96 between different body forms and different invasion depth.Though the differences were not siginificant,it still could prove the mechanism between different body forms and different invasion depth were various.
2、The expression of nm23 was less in gastric cancer samples than in chronic gastritis samples or in peptic ulcer samples,which suggested it involved in carcinogenesis of human gastric cancer.while we detected lowgrade gastric cancer23 had a relationship with metastasis function in gastric cancer.There were some differences about expression of nm23 between different body forms and different invasion depth.Tough the differences were not siginificant,it still could prove the mechanism between different body forms and different invasion depth were various.
3、There was significantly positive association about HSPgp96 expression in the occurrence、development of gastric cancer,while there was significantly negative association about nm23 expression. There was positive association about HSPgp96 expression among differentiated degree、lymph node metastasis and TNM type in different clinical stages of gastric cancer. There was significantly negative association about nm23 expression among them. Our experiment suggested there may be exist cooperation between HSPgp96 and nm23 in the occurrence、development、metastasis of gastric cancer. Thus we hope to supply a theoretical evidence for early diagnosis and Judgement of prognosis through checking HSPgp96 and nm23 in gastric cancer.The strength of its expression hopes to become a hand which guides a clinical treatment.
通过检测慢性胃炎、消化性溃疡及胃癌组织中热休克蛋白gp96和nm23的表达,探讨它们在胃癌的发生发展及转移中作用和可能的分子机制,为胃癌的早期诊断、治疗方案制定、预后判断和肿瘤的分子治疗等提供理论基础。
方法:
应用免疫组织化学的方法检测慢性胃炎、消化性溃疡及胃癌组织中热休克蛋白gp96和nm23的表达情况,并分析它们与各临床病理参数之间的关系,应用SPSS11.5统计软件包进行卡方(x~2)数据处理。
结果:
1、试验组40例胃癌组织中HSPgp96和nm23的表达阳性率分别为67.5%和37.5%。HSPgp96的阳性率试验组显著高于对照组(慢性胃炎35%;消化性溃疡40%),且其差异性具有统计学意义(x~2 =5.74,P<0.05;x~2 =4.15, P<0.05);nm23的阳性率试验组明显低于对照着(慢性胃炎70%;消化性溃疡75%),且其差异性具有统计学意义(x~2 =5.64, P<0.05;x~2 =7.5,P<0.05)。
2、不同临床病理分期的胃癌组织中HSPgp96的表达阳性率不同:低分化组(72.7%)显著高于中、高分化组(38.9%),且其差异性具有统计学意义(x~2 =4.639,P<0.05);有淋巴结转移组(69.6%)显著高于无淋巴结转移组(29.4%),其差异性具有统计学意义(x~2 =6.32,P<0.05);TNM分型中III—IVI组(70.8%)显著高于I—II组(37.5%),其差异性具有统计学意义(x~2 =4.365,P<0.05)。大体形态中局限型(57.9%)与浸润型(57.1%)的差异性无统计学意义(x~2 =0.0023,P>0.05);侵犯深度中mps0(57%)与mps1-3(61.5%)的差异性无统计学意义(x~2 =0.0732, P>0.05)。
3、不同临床病理分期的胃癌组织中nm23的表达阳性率不同:低分化组(36.4%)显著低于中、高分化组(72.2%),且其差异性具有统计学意义(x~2 =5.1045,P<0.05);有淋巴结转移组(34.8%)显著低于无淋巴结转移组(70.6%),其差异性具有统计学意义(x~2 =5.013,P<0.05);TNM分型中Ⅲ—Ⅳ组(41.7%)显著低于I—II组(75%),其差异性具有统计学意义(x~2 =4.309,P<0.05)。大体形态中局限型(42.1%)与浸润型(42.9%)的差异性无统计学意义(x~2 =0.0023,P>0.05);侵犯深度中mps0(64.3%)与mps1-3(57.7%)的差异性无统计学意义(x~2 =0.1648,P>0.05)。
结论:
1、胃癌组织细胞中热休克蛋白gp96表达明显高于慢性胃炎及消化性溃疡,这提示了热休克蛋白gp96参与胃癌的发生。而在低分化胃癌的组织中的表达明显高于中高分化胃癌;有淋巴结转移的胃癌组织中的表达明显高于无淋巴结转移者;TNM分型中III+IV组织中的表达明显高于I+II型,说明了它与肿瘤的浸润转移密切相关;而不同大体形态及侵犯深度中,热休克蛋白gp96表达存在差异,这也从另一个侧面反应了热休克蛋白gp96在肿瘤大体形态及侵犯深度中的作用机制可能不同。2、胃癌组织细胞中nm23表达明显低于慢性胃炎及消化性溃疡,这提示了nm23与胃癌的形成有关。而在低分化胃癌的组织中的表达明显低于中高分化胃癌;有淋巴结转移的胃癌组织中的表达明显低于无淋巴结转移者;TNM分型中III+IV组织中的表达明显低于I+II型,说明了它与肿瘤的浸润转移密切相关;而不同大体形态及侵犯深度中,nm23表达存在差异,这也从另一个侧面反应了nm23在肿瘤大体形态及侵犯深度中的作用机制可能不同。
3、在胃癌的形成中,与热休克蛋白gp96表达呈正相关,而与nm23的表达呈负相关;在胃癌不同的临床病理分期中,热休克蛋白gp96与分化程度、淋巴结转移,TNM分型表达呈正相关;而nm23与之相反。试验表明热休克蛋白gp96及nm23在胃癌的形成和浸润转移中存在着协同作用。因而热休克蛋白gp96及nm23可作为胃癌的早期诊断、判断肿瘤预后的指标检测,其表达强度的高低有望成为指导临床治疗的一个手段。
Objective:
To make clear the roles which HSPgp96 and nm23 played in the occurrence、development、metastasis of chronic gastritis、peptic ulcer、gastric cancer and probable molecular mechanism of them,we intended to detect the expression of them and analyzed the relationship among them.we hope to supply a theoretical evidence for early diagnosis、cure a project、judgment of prognosis and tumor therapy.
Methods:
we applied SP immunohistochemical method to detect HSPgp96 and nm23 protein expressions and analyzed theirs relationship with each other in gastric cancer containing chronic gastritis、peptic ulcer.All date were processed by SPSS 11.5 analysis software to progress Chi-square test.
Results:
1、HSPgp96 and nm23 proteins were respectively detected in 67.5% and 37.5% of all 40 gastric cancer. HSPgp96 of testing group was higher than those of control group(chronic gastritis 35%、peptic ulcer 40%),and the differences were statistically significant(p<0.05). nm23 of testing group was less than those of control group(chronic gastritis 70%、peptic ulcer 75%),and the differences were statistically significant(p<0.05).
2、The expressions of HSPgp96 in different clinical pathology stages of gastric cancer were various: lowgrade(72.7%)>high-middlegrade(38.9%), the differences were statistically significant(x~2=4.639,p<0.05).With lymph node metastasis(69.9%)> Without lymph node metastasis(29.4%), the differences were statistically significant(x~2=6.32,p<0.05).In the TNM cent type,III+IV(70.8%)>I+II(37.5%), the differences were statistically significant(x~2=4.365,p<0.05). The differences between limited type(57.9%) and invaded type(57.1%)in the body form were not statistically significant(x~2=0.0023,p>0.05). The differences between MPSo(57%) and MPS 1-3(61.5%) in the invasion depth were not statistically significant (x~2=0.0732, p>0.05).
3、The expressions of nm23 in different clinical pathology stages of gastric cancer were various: lowgrade(36.4%)< high-middlegrade(72.2%), the differences were statistically significant(x~2=5.1045, p<0.05). With lymph node metastasis (34.8%)< Without lymph node metastasis(70.6%), the differences were statistically significant(x~2=5.013, p<0.05). In the TNM cent type,III+IV(41.7%)< I+II(75%), the differences were statistically significant(x~2=4.309, p<0.05). The differences between limited type(42.1%) and invaded type(42.9%) in the body form were not statistically significant(x~2=0.0023,p>0.05). The differences between MPSo(64.3%) and MPS1-3(57.7%) in the invasion depth were not statistically significant (x~2=0.1648, p>0.05).
Conclusion:
1、The expression of HSPgp96 was much higher in gastric cancer samples than in chronic gastritis samples or in peptic ulcer samples,which suggested it involved in carcinogenesis of human gastric cancer.while we detected lowgrade gastric cancer >high-middlegrade gastric cancer ; gastric cancer with lymph node metastasis> without lymph node metastasis; In the TNM cent type,III+IV>I+II, which proved HSPgp96 had a relationship with metastasis function in gastric cancer.There were some differences about expression of HSPgp96 between different body forms and different invasion depth.Though the differences were not siginificant,it still could prove the mechanism between different body forms and different invasion depth were various.
2、The expression of nm23 was less in gastric cancer samples than in chronic gastritis samples or in peptic ulcer samples,which suggested it involved in carcinogenesis of human gastric cancer.while we detected lowgrade gastric cancer
3、There was significantly positive association about HSPgp96 expression in the occurrence、development of gastric cancer,while there was significantly negative association about nm23 expression. There was positive association about HSPgp96 expression among differentiated degree、lymph node metastasis and TNM type in different clinical stages of gastric cancer. There was significantly negative association about nm23 expression among them. Our experiment suggested there may be exist cooperation between HSPgp96 and nm23 in the occurrence、development、metastasis of gastric cancer. Thus we hope to supply a theoretical evidence for early diagnosis and Judgement of prognosis through checking HSPgp96 and nm23 in gastric cancer.The strength of its expression hopes to become a hand which guides a clinical treatment.
引文
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[1] 陈锡美,许树长。胃癌概述。胃粘膜疾病基础与临床研究。2004,1;163
[2] Niki M ,Isozaki H,Toyoda M , et al . Serum human hepatocyte growth factor ( hHGF) is elevated in patients with metastatic gastric carcinoma[J]. Hepatogastroenterology, 1998 ,45(24) :2458 - 2463.
[3] Taniguchi K, Yonemura Y,Nojima N , et al . The relationship between the growth patterns of gastric carcinoma and expression of hepatocyte growth factor receptor (c-met) ,antocrine motility factor receptor , and urokinase-type plasminogen activator receptor [J ]. Cancer ,1998 ,82(11) :2112- 2122.
[4] Altorki N , Schwartz GK , Blundell M , et al. Characterization of all lines established from human gastric - esophageal adenocarcinoma : biological phenotype and invasion potential Cancer ,1993 ;72 :649～654
[5] Senota A , Itoh F , Yamanoto H , et al. Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer.Clin Exp Metastasis ,1998 ;16 :313～321
[6] 陈锡美,许树长。胃癌的侵袭转移机制。胃粘膜疾病基础与临床研究。2004,1;199
[7] Tanaka N , Fukao H , Ueshima S , et al. Plaminogen activator inhibitor 1 in human carcinoma tissue. Int J Cancer ,1991 ; 48 :481～484
[8] 陈天池, 魏品康。细胞间黏附分子与胃癌侵袭、转移关系的研究进展。世界华人消化杂志 2006; 14(26): 2613-2616。
[9] 陆岽.陈玉丽.王承党. CD44 V6和MMP-9在胃癌及癌前病变组织中表达. 胃肠病学和肝病学杂志.2005;14(6);597-600.
[10] Ura H,Denno R ,Hirata K, et al . Separate functions of alpha2beta1 and alph3beta1 integrins in the metastatic process of human gastric carcinoma[J ]. Surg Today ,1998 ,28(10) :1001 - 1006.
[11] Kabashima A ,Maehara Y,Kakeji ,et al . Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph metastasis[J ] . Clin ancer Res ,2000 ;6 (9) :3581 -3584
[12] 王栋, 徐垚, 耿鑫, 张维铭。上皮钙粘蛋白与胃癌浸润转移的关系 天津医科大学学报2005:11(4)531-536
[13] Kamiyama M, Ichikawa Y, Ishikawa T ,et al . VEGF receptor antisens therapy inhibits angiogenesis and peritonesl dissemination of human gastric and peritoneal dissemination of human gastric cancer in nudemice [J ] . Cancer Gene Ther ,2002 ;90(13) :197
[14] Liao X, Tang W,Cai Q. Lymphangiogenesis in tumor tissues and 5-Nase ,Flt-4 ,Flk-1 ,expression[J ] . Clin Med J ,2000 ;113(11) :1031
[15] Yonemura Y, Fushida S ,Bando E , et al . Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR) 23 in gastric cancer[J ] . Eur J Cancer ,2001 ;37(7) :918
[16] 赵仲生,姚根有,茹国庆,马杰,阮俊。碱性成纤维细胞生长因子和基质金属蛋白酶一9 mRNA表达与胃癌临床病理学及生存期的关系 。中华外科杂志。2005:43(3),169-173
[17] 张真真,张声. 促血管生成素及受体的异常表达于胃癌血管生成的关系[J ] . 中华肿瘤杂志,2006 ;28(4) :280 - 284
[18] 陈锡美,许树长。幽门螺杆菌与胃粘膜疾病。肿瘤免疫;2004.1,201
[19] 周丹秋 ,李敏,吕元. C2erbB22 、nm23 与胃癌生物学特性的关系研究[J ]. 临床检验杂志:2005:23(1):28-30
[20] 赵茜,区穗芳,谢秀琴. p53 及nm23 在胃癌中的表达及其与淋巴结转移的关系[J ]. 中国热带医学 ;2007:7(5):689—690.
[21] Kakeji Y,Koenig D ,Tsujitani S ,et al . Gastric cancer with p53 over expression has high potential for metastasizing to lymph nodes [J ] . Br J Cancer ,1993 ;67 (3) :589 - 593
[22] 周烨,朱慰祺,师英强等. 血管内皮生长因子和抑癌基因p53 在胃癌中的表达及临床意义[J ] . 中国癌症杂志,2003 ;13 (1) :9 -12
[23] 赵鹏,王静芬,赵家宏,白雪峰.胃癌rasp21和nm23基因表达联合检测意义研究[J]. 伤残医学杂志2002:10[4];12-14
[24] Guan-Zhen Y, Ying C, Can-Rong N, Guo-Dong W, Jian-Xin Q, Jie-Jun W. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer.[J]. Int J Exp Pathol. 2007 Jun;88(3):175-183.
[25] Yamada T,Nakamura R,Kido K et a1.Function of hsp90 in differentiation and apoptosis of human Ec cells ,Trans Soc Pathol Jpn,1995;84(1):217.
[26] Gething MJ,Sambrook J.Protein folding in the cel1.Nature,1992,335(6355):33-35
[27] 袁玫. 热休克蛋白台复合物用于肿瘤的免疫治疗[J ] .国外医学: 肿瘤分册, 2003 , 30 (1) : 20.
[28] Graner M , Raymond A , Romney D , et al. Immunoprotoctive activities of Multiple chaperone proteins isolated from murine B-cell leukemia/ lymphoma [ J ] . Clin Cancer Res ,2000 , 6 (3) : 909.
[29] 杨峻峰, 胡伟, 熊咏, 袁爱军, 田明国. 热休克蛋白gp96 在人胃癌组织中的表达及与胃癌生物学行为的关系.[J] 实用临床医药杂志;2006:10(3):109-110
[30] Xiao-Ping Wang .Qiao-Xia Wang.and Xiao-Ping Ying.Correlation between Cliniopathology and Expression of Heat Shock Protein 72 and Glycoprotein 96 in Human Gastric Adenocarcinoma .Tohoku J Exp.Med:2007:212:35-41
[2] Yamada T,Nakamura R,Kido K et a1.Function of hsp90 in differentiation and apoptosis of human Ec cells ,Trans Soc Pathol Jpn,1995;84(1):217.
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[4] 袁玫. 热休克蛋白台复合物用于肿瘤的免疫治疗[J ] .国外医学: 肿瘤分册, 2003 , 30 (1) : 20.
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[11] Guan-Zhen Y, Ying C, Can-Rong N, Guo-Dong W, Jian-Xin Q, Jie-Jun W. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer.[J]. Int J Exp Pathol. 2007 Jun;88(3):175-183
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[1] 陈锡美,许树长。胃癌概述。胃粘膜疾病基础与临床研究。2004,1;163
[2] Niki M ,Isozaki H,Toyoda M , et al . Serum human hepatocyte growth factor ( hHGF) is elevated in patients with metastatic gastric carcinoma[J]. Hepatogastroenterology, 1998 ,45(24) :2458 - 2463.
[3] Taniguchi K, Yonemura Y,Nojima N , et al . The relationship between the growth patterns of gastric carcinoma and expression of hepatocyte growth factor receptor (c-met) ,antocrine motility factor receptor , and urokinase-type plasminogen activator receptor [J ]. Cancer ,1998 ,82(11) :2112- 2122.
[4] Altorki N , Schwartz GK , Blundell M , et al. Characterization of all lines established from human gastric - esophageal adenocarcinoma : biological phenotype and invasion potential Cancer ,1993 ;72 :649～654
[5] Senota A , Itoh F , Yamanoto H , et al. Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer.Clin Exp Metastasis ,1998 ;16 :313～321
[6] 陈锡美,许树长。胃癌的侵袭转移机制。胃粘膜疾病基础与临床研究。2004,1;199
[7] Tanaka N , Fukao H , Ueshima S , et al. Plaminogen activator inhibitor 1 in human carcinoma tissue. Int J Cancer ,1991 ; 48 :481～484
[8] 陈天池, 魏品康。细胞间黏附分子与胃癌侵袭、转移关系的研究进展。世界华人消化杂志 2006; 14(26): 2613-2616。
[9] 陆岽.陈玉丽.王承党. CD44 V6和MMP-9在胃癌及癌前病变组织中表达. 胃肠病学和肝病学杂志.2005;14(6);597-600.
[10] Ura H,Denno R ,Hirata K, et al . Separate functions of alpha2beta1 and alph3beta1 integrins in the metastatic process of human gastric carcinoma[J ]. Surg Today ,1998 ,28(10) :1001 - 1006.
[11] Kabashima A ,Maehara Y,Kakeji ,et al . Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph metastasis[J ] . Clin ancer Res ,2000 ;6 (9) :3581 -3584
[12] 王栋, 徐垚, 耿鑫, 张维铭。上皮钙粘蛋白与胃癌浸润转移的关系 天津医科大学学报2005:11(4)531-536
[13] Kamiyama M, Ichikawa Y, Ishikawa T ,et al . VEGF receptor antisens therapy inhibits angiogenesis and peritonesl dissemination of human gastric and peritoneal dissemination of human gastric cancer in nudemice [J ] . Cancer Gene Ther ,2002 ;90(13) :197
[14] Liao X, Tang W,Cai Q. Lymphangiogenesis in tumor tissues and 5-Nase ,Flt-4 ,Flk-1 ,expression[J ] . Clin Med J ,2000 ;113(11) :1031
[15] Yonemura Y, Fushida S ,Bando E , et al . Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR) 23 in gastric cancer[J ] . Eur J Cancer ,2001 ;37(7) :918
[16] 赵仲生,姚根有,茹国庆,马杰,阮俊。碱性成纤维细胞生长因子和基质金属蛋白酶一9 mRNA表达与胃癌临床病理学及生存期的关系 。中华外科杂志。2005:43(3),169-173
[17] 张真真,张声. 促血管生成素及受体的异常表达于胃癌血管生成的关系[J ] . 中华肿瘤杂志,2006 ;28(4) :280 - 284
[18] 陈锡美,许树长。幽门螺杆菌与胃粘膜疾病。肿瘤免疫;2004.1,201
[19] 周丹秋 ,李敏,吕元. C2erbB22 、nm23 与胃癌生物学特性的关系研究[J ]. 临床检验杂志:2005:23(1):28-30
[20] 赵茜,区穗芳,谢秀琴. p53 及nm23 在胃癌中的表达及其与淋巴结转移的关系[J ]. 中国热带医学 ;2007:7(5):689—690.
[21] Kakeji Y,Koenig D ,Tsujitani S ,et al . Gastric cancer with p53 over expression has high potential for metastasizing to lymph nodes [J ] . Br J Cancer ,1993 ;67 (3) :589 - 593
[22] 周烨,朱慰祺,师英强等. 血管内皮生长因子和抑癌基因p53 在胃癌中的表达及临床意义[J ] . 中国癌症杂志,2003 ;13 (1) :9 -12
[23] 赵鹏,王静芬,赵家宏,白雪峰.胃癌rasp21和nm23基因表达联合检测意义研究[J]. 伤残医学杂志2002:10[4];12-14
[24] Guan-Zhen Y, Ying C, Can-Rong N, Guo-Dong W, Jian-Xin Q, Jie-Jun W. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer.[J]. Int J Exp Pathol. 2007 Jun;88(3):175-183.
[25] Yamada T,Nakamura R,Kido K et a1.Function of hsp90 in differentiation and apoptosis of human Ec cells ,Trans Soc Pathol Jpn,1995;84(1):217.
[26] Gething MJ,Sambrook J.Protein folding in the cel1.Nature,1992,335(6355):33-35
[27] 袁玫. 热休克蛋白台复合物用于肿瘤的免疫治疗[J ] .国外医学: 肿瘤分册, 2003 , 30 (1) : 20.
[28] Graner M , Raymond A , Romney D , et al. Immunoprotoctive activities of Multiple chaperone proteins isolated from murine B-cell leukemia/ lymphoma [ J ] . Clin Cancer Res ,2000 , 6 (3) : 909.
[29] 杨峻峰, 胡伟, 熊咏, 袁爱军, 田明国. 热休克蛋白gp96 在人胃癌组织中的表达及与胃癌生物学行为的关系.[J] 实用临床医药杂志;2006:10(3):109-110
[30] Xiao-Ping Wang .Qiao-Xia Wang.and Xiao-Ping Ying.Correlation between Cliniopathology and Expression of Heat Shock Protein 72 and Glycoprotein 96 in Human Gastric Adenocarcinoma .Tohoku J Exp.Med:2007:212:35-41