几种恶性肿瘤患者外周血细胞CD44V5的检测

目的　探讨不同恶性肿瘤患者外周血细胞肿瘤转移基因的表达规律。方法　采用流式细胞术对 187例各种恶性肿瘤 (包括肺癌、胃癌、骨肉瘤、胸腺瘤、大肠癌等 )患者外周血细胞CD44V5 ( +)细胞检出率进行了检测和分析。结果　大部分恶性肿瘤患者外周血细胞CD44V5 ( +)细胞检出率均显著高于正常对照组 (P <0 0 1) ,仅乳腺癌患者外周血CD44V5 ( +)细胞的表达率与正常对照无显著差异 (P >0 0 5 )。在胃癌和大肠癌患者中 ,伴有转移者外周血细胞CD44V5 ( +)检出率显著高于未转移者 (P <0 0 1)。结论不同恶性肿瘤患者的外周血细胞CD44V5基因表达率不同。CD44V5检测还可能对肿瘤恶性程度和预后判断有重要价值     

肺癌患者外周血细胞CD_(25)、CD_4表达和Apo水平的检测

目的 :研究肺癌患者外周血细胞CD2 5、CD4表达规律和Apo水平。方法 :采用流式细胞术对10 1例肺癌患者外周血细胞CD2 5 、CD3 CD4 表达率和Apo水平进行了检测。并分析了肿瘤转移状况和化疗对上述 3项指标的影响。结果 :肺癌患者外周血细胞CD2 5 和CD3 CD4 率均显著低于正常对照组 (P <0 0 1和P <0 0 5 ) ,Apo显著高于正常对照组 (P <0 0 1)。化疗者的 3项指标均显著高于未化疗者 (P <0 0 1,P <0 0 5和P <0 0 5 ) ;在未化疗患者中 ,有转移者和无转移者之间的CD2 5和CD3 CD4表达率差异均无显著性 (P >0 0 5 ) ,而转移者的Apo却显著高于无转移者 (P <0 0 1) ;在化疗患者中 ,转移者的Apo表达率显著高于无转移者 (P <0 0 1) ,CD2 5 表达率低于无转移者 (P <0 0 5 ) ,而CD3 CD4 二者差异却无显著性 (P >0 0 5 )。结论 :肺癌能抑制患者外周血细胞CD2 5 和CD3 CD4 细胞进一步降低 ,但却引起Apo明显升高。化疗可以提高肿瘤患者CD2 5 、CD3 CD4 和Apo的检出率 ,使机体免疫功能能有所恢复     

CD44s和CD44v6的mRNA在胃癌中的表达及其临床意义

目的　探讨CD4 4smRNA和CD4 4v6mRNA在胃癌中的表达及其临床意义。方法　应用巢式RT PCR检测 16例远隔癌灶部位“正常”胃黏膜及 5 8例胃癌新鲜组织中CD4 4smRNA和CD4 4v6mRNA表达水平。结果　CD4 4smRNA在胃癌组织和远隔癌灶部位“正常”胃黏膜中的表达无差异 ,和胃癌的各临床病理学指标无关 (P >0 .0 5 )。CD4 4v6mRNA在胃癌组织中的表达高于远隔癌灶部位“正常”胃黏膜 (P <0 .0 5 ) ,与Borrmann分型 (P <0 .0 5 )、脉管侵犯 (P <0 .0 1)、浆膜浸润 (P <0 .0 1)和淋巴结转移 (P <0 .0 1)有关。结论　CD4 4smRNA和胃癌的发生发展无关 ,CD4 4v6与胃癌的浸润及转移相关。     

肿瘤转移抑制基因编码蛋白在癌患者外周血中的表达

目的　探讨肿瘤转移抑制基因编码蛋白在癌患者外周血细胞中的表达规律。方法　采用流式细胞术对 173例各种癌患者外周血nm2 3 +、DCC +、p16+和p5 3V +细胞检出率进行检测。结果　恶性肿瘤患者外周血nm2 3 +、DCC +和p16+细胞检出率均显著低于正常对照 (P <0 0 1或P <0 0 5 ) ,但分布各有不同 ;而p5 3V +细胞检出率显著高于正常对照组 (P <0 .0 5 )。癌转移者外周血nm2 3 +、DDC +和p16+的表达水平显著低于未转移者 (P <0 .0 1)或P <0 .0 5 ) ,而p5 3V则相反。结论　恶性肿瘤能使患者外周血细胞的肿瘤转移抑制基因抑编码蛋白表达水平出现明显异常 ,而这种异常表达与恶性肿瘤转移的关系十分密切 ;不同肿瘤患者异常表达的肿瘤转移抑制基因类型有一定的倾向性。     

几种恶性肿瘤患者外周血细胞CD44V5的检测

目的 探讨不同恶性肿瘤患者外周血细胞肿瘤转移基因的表达规律。方法 采用流式细胞术对187例各种恶性肿瘤（包括肺癌，胃癌，骨肉瘤，胸腺瘤，大肠癌等）患者外周血细胞CD44V5（＋）细胞检出率进行了检测和分析。结果 大部分恶性肿瘤患者外周血细胞CD44V5（＋）细胞检出率均显著高于正常对照组（P＜0．01），仅乳腺癌患者外周血CD44V5（＋）细胞的表达率与正常对照无显著差异（P＞0．05）。在胃癌和大肠癌患者中，伴有转移者外周血细胞CD44V5（＋）检出率显著高于未转移者（P＜0．01）。结论 不同恶性肿瘤患者的外周血细胞CD44V5基因表达率不同。CD44V5检测还可能对肿瘤恶性程度和预后判断有重要价值。     

大肠癌患者外周血细胞CD44s和CD44V5及CD44V6 表达的研究

目的探讨大肠癌患者外周血细胞 CD44s、CD44V5 和 CD44V6的表达与肿瘤转移和预后的关系.方法采用流式细胞术对 62 例大肠癌患者外周血细胞 CD44s、CD44V5 和 CD44V6 的表达率进行检测,并分析他们之间的相关性.结果大肠癌患者外周血细胞的 CD44V5+ 细胞和 CD44V6+ 细胞检出率均显著高于正常对照组,P<0.01;且转移者显著高于未转移者,P＜0.01;而 CD44s+ 细胞检出率却显著低于正常对照组,P<0.05;且伴转移者显著低于未转移者,P<0.01;肿瘤患者外周血细胞 CD44V5+ 和 CD44V6+ 细胞表达率与 CD44s+ 细胞检出率呈显著的负相关,r1=0.84,P1<0.05和r2=-0.87,P2<0.01.结论CD44V5 及 CD44V6 的表达与肿瘤转移密切相关,检测大肠癌患者外周血中的 CD44s、CD44V 及 CD44V6 的表达可为肿瘤的发生、发展及预后判断提供依据.     

肿瘤转移相关基因在恶性肿瘤组织中的表达及其临床意义

 目的　探讨各种肿瘤转移相关基因编码蛋白在恶性肿瘤转移中的表达规律及其临床意义。方法　采用流式细胞术对 5 6例肿瘤转移和 6 1例肿瘤未转移患者瘤组织的CD4 4V5 +、CD4 4V6 +、c erbB 2 +、nm2 3+、DCC +和p16 +细胞检出率和DNA含量进行了检测和分析。结果　恶性肿瘤患者瘤组织细胞的CD4 4V5 +、CD4 4V6 +和c erbB 2 +细胞表达率均显著高于正常对照组 (P <0 .0 1或P <0 .0 5 ) ;nm2 3+,DCC +,p16 +细胞表达率则显著低于正常对照组 (P <0 .0 1或P <0 .0 5 )。肿瘤转移者、多器官转移者、DNA异倍体者、SPF增高者、Apo减低者的CD4 4V5 +、CD4 4V6 +、c erbB 2 +细胞表达率均显著高于未转移者、单器官转移者、DNA二倍体者、SPF不增高者、Apo不减低者 (P <0 .0 1或P <0 .0 5 )。而nm2 3+、DCC +、p16 +细胞的表达率与此相反。结论　肿瘤组织肿瘤转移相关基因编码蛋白表达水平的检测 ,对肿瘤的恶性度、转移潜能、转移严重程度及患者预后估计有重要价值。     

瘤组织和外周血细胞中肿瘤转移促进基因表达的对比研究

目的　探讨恶性肿瘤患者肿瘤组织和外周血细胞中肿瘤转移促进基因表达的相关性。方法　采用流式细胞术对恶性肿瘤患者肿瘤组织和外周血细胞中CD44V 5、CD 44V 6和c erbB 2表达进行检测和分析。结果　恶性肿瘤患者的肿瘤组织和外周血细胞中CD 44V 5、CD44V 6和c erbB 2表达率均显著高于正常对照组 (P <0 .0 1和P <0 .0 5 )。肿瘤转移者CD 44V 5、CD44V 6和c erbB 2表达率均显著高于未转移者 (P <0 .0 1和P <0 .0 5 )。肿瘤患者肿瘤组织和外周血细胞中CD44V 5、CD 44V 6表达率均呈良好的正相关关系 (γ1=0 .3 62 2 ,P <0 .0 5 ;γ2 =0 .3 83 3 ,P <0 .0 5 ) ,而c erbB 2表达率不呈正相关关系。结论　肿瘤转移促进基因与肿瘤转移的关系十分密切。检测肿瘤患者外周血细胞CD44V 5和CD 44V 6表达有助于肿瘤预后的判断     

肺癌患者外周血细胞CD25、CD4表达和Apo水平的检测

目的研究肺癌患者外周血细胞CD25、CD4表达规律和Apo水平.方法采用流式细胞术对101例肺癌患者外周血细胞CD25+、CD3+/CD4+表达率和Apo水平进行了检测.并分析了肿瘤转移状况和化疗对上述3项指标的影响.结果肺癌患者外周血细胞CD25+和CD3+/CD4+率均显著低于正常对照组(P＜0.0l和P＜0.05),Apo显著高于正常对照组(P＜0.01).化疗者的3项指标均显著高于未化疗者(P＜0.0l,P＜0.05和P＜0.05);在未化疗患者中,有转移者和无转移者之间的CD25和CD3/CD4表达率差异均无显著性(P＞0.05),而转移者的Apo却显著高于无转移者(P＜0.01);在化疗患者中,转移者的Apo表达率显著高于无转移者(P＜0.01),CD25+表达率低于无转移者(P＜0.05),而CD3+/CD4+二者差异却无显著性(P＞0.05).结论肺癌能抑制患者外周血细胞CD25+和CD3+/CD4+细胞进一步降低,但却引起Apo明显升高.化疗可以提高肿瘤患者CD25+、CD3+/CD4+和Apo的检出率,使机体免疫功能能有所恢复.     

卵巢癌血清CA125浓度与血细胞生物学指标的相关性研究

目的 :探讨卵巢癌患者血清CA12 5表达水平与血细胞生物学指标的相关性。方法 :采用酶联免疫分析和流式细胞术 ,对 33例卵巢癌患者血清CA12 5浓度和血细胞p5 3V+ 、CD44s+ 、p170 + 和Apo+ 细胞检出率进行了检测。结果 :卵巢癌患者CA12 5浓度、p5 3V+ 细胞的百分率均显著高于正常对照组 ,P<0 0 1,CD44s+ 细胞表达率却显著低于正常对照组 ,P <0 0 5 ,随着患者血清CA12 5浓度的增加 ,血细胞的p5 3V+ 细胞表达率逐渐升高 ,并呈显著的正相关 ,r =0 989,P <0 0 1,CD44s+ 细胞表达率逐渐降低 ,并呈显著的负相关 ,r =- 0 910 ,P <0 0 5。结论 :卵巢癌患者血清CA12 5浓度与p5 3V+ 细胞表达率、CD44s+ 细胞表达率、肿瘤临床分期以及肿瘤转移的关系都十分密切     

CD44v6与可溶性CD44v6在胃癌中的表达及与预后的关系

目的 探讨CD44v6与可溶性CD44v6(sCD44v6)在胃癌中的表达及与胃癌生物学行为和预后的关系.方法 应用免疫组化S-P法检测103例胃癌组织和10例正常胃黏膜标本的CD44v6表达,并对患者进行术后随访,随访期为3～91个月;应用酶联免疫吸附(ELISA)法检测86例胃癌、30例胃溃疡患者和30例健康人外周血血清中sCD44v6的浓度,并对患者进行术后随访,随访期为1～91个月.结果 (1)CD44v6在正常胃黏膜中不表达,而在胃癌中的表达率为60.2%;CD44v6的表达与淋巴结转移、TNM分期、脉管是否存在癌栓以及Borrmann分型有关(P＜0.05),而与胃癌浸润深度、是否远处转移、分化程度以及患者的生存率无关(P＞0.05);9例伴有肝转移的胃癌患者中,有7例CD44v6为强阳性表达.(2)胃癌患者外周血血清中sCD44v6的浓度明显高于胃溃疡组和健康对照组(P＜0.01);胃癌根治术后患者血液中sCD44v6的浓度比术前明显下降(P＜0.01),而姑息术后患者的浓度变化却不明显(P＞0.05);sCD44v6的浓度与胃癌浸润深度、淋巴结转移、是否远处转移、脉管是否存在癌栓、Borrmann分型以及分化程度无关;sCD44v6浓度较高组的生存率较sCD44v6浓度较低组高,且差异有统计学意义(P=0.0281),但经Cox回归分析显示,sCD44v6的浓度与生存期有关(P=0.415),而手术方式却与生存期有关(P=0.000).(3)胃癌组织中CD44v6的表达与外周血血清中sCD44v6的表达无明显平行关系(P＞0.05).结论 CD44v6的表达对评估胃癌生物学行为有参考价值,但是否与预后有关仍需探讨;sCD44v6的表达对胃癌辅助诊断、手术彻底性判定及生物学行为评估有一定的意义;CD44v6与sCD44v6的表达无明显平行关系.     

胃癌组织及区域淋巴结MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系

背景与目的:研究证实胃癌浸润深度和淋巴结转移是多基因及其蛋白表达产物协调作用的结果,寻找与胃癌转移相关的分子生物学标志物有助于胃癌的研究。本实验旨在探讨胃癌组织及区域淋巴结中MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系。方法:采用SP免疫组织化学方法对110例胃癌组织及613枚区域淋巴结中的MUC1、CD44v6、nm23基因蛋白的表达进行检测。结果:①胃癌组织中的MUC1蛋白阳性表达在低分化癌组、浸润型组、T3+T4组、淋巴结转移组、Ⅲ～Ⅳ期组、生存期<5年组分别为84.6%、88.1%、87.3%、91.7%、94.4%、95.5%,CD44v6分别为79.5%、74.6%、79.4%、81.7%、87.0%、87.9%,nm23分别为38.5%、32.2%、30.2%、25.0%、25.9%、18.2%。MUC1和CD44v6表达低分化癌组显著高于高、中分化癌组(78.9%vs57.7%),浸润型组高于局限型组(72.6%vs54.9%),T3+T4组高于T2组(72.3%vs46.8%),淋巴结转移组高于无淋巴结转移组(68.0%vs46.0%),TNMⅢ～Ⅳ期组高于Ⅰ～Ⅱ期组(67.9%vs44.6%),生存期<5年组高于≥5年组(59.1%vs31.8%),各组间差异均具有显著性(P<0.01或P<0.05)。而nm23除分化程度、Borrmann分型不同的两组之间差异无显著性外,T3+T4组低于T2组(51.1%),有淋巴结转移组低于无淋巴结转移组(56.0%),TNMⅢ～Ⅳ期组低于Ⅰ～Ⅱ     

胃癌及区域淋巴结CD44v6、nm23-H1表达与其病理特征及预后关系的研究

目的:探讨胃癌及其区域淋巴结CD44V6、nm23-H1表达与胃癌病理特征及预后的关系.方法:本研究采用SP免疫组织化学方法对110例胃癌及613枚区域淋巴结组织中的CD44V6、nm23-H1的表达进行检测.结果:在胃癌原发灶和在淋巴结转移灶,CD44V6阳性表达率分别为65.5%和89.4%,nm23-H1阳性表达率分别为39.1%和16.8%.CD44V6、nm23-H1表达率与胃癌的组织学类型、浸润深度、淋巴结转移密切相关.胃癌原发灶CD44V6阳性表达组5年生存率显著低于阴性表达组(P＜0.01);nm23-H1阳性表达组5年生存率显著高于阴性表达组(P＜0.01).结论:对胃癌组织进行CD44V6、nm23-H1蛋白的检测,有助于预测胃癌进程和淋巴结转移的诊断,以及评估胃癌患者的预后.     

Co-expression of osteopontin and CD44v9 in gastric cancer

We have examined the expression of osteopontin (OPN) in 40 human primary gastric carcinoma tissues, 5 metastatic foci (lymph nodes) and corresponding normal mucosas. Twenty-nine of 40 primary tumors (72.5%) and 3 of 5 lymph node metastases (60%) overexpressed OPN mRNA in comparison with those of the corresponding normal mucosa. The incidence as well as relative expression level of OPN mRNA was higher in well differentiated gastric cancers than poorly differentiated ones. Moreover, increased OPN mRNA expression in primary tumor specimens was observed along with the advancement of the clinico-pathological stage. Using in situ hybridization (ISH) analysis, not only inflammatory cells in tumor stroma but also tumor cells showed positive signals for OPN mRNA. By immunohistochemistry, co-immunoreaction of OPN and CD44v9 in tumor cells obviously correlated with the degree of lymphatic vessel invasion or long distant lymph node metastases in poorly differentiated gastric cancer. Interestingly, strong co-immunoreaction of OPN and CD44v9 of tumor cells was concommitant with cluster formation in the lymphatic vessels. Our results suggest that overexpression of OPN correlated with the progression of human gastric carcinoma. Especially in CD44-bearing poorly differentiated gastric cancer, interaction between OPN and CD44 may parallel lymphogenous metastasis. Int. J. Cancer (Pred. Oncol.) 79:127–132, 1998.© 1998 Wiley-Liss, Inc.     

4-1BB/4-1BBL在胃癌组织及其外周血中的表达及临床意义

目的探讨胃癌局部免疫与全身免疫状态。方法应用流式细胞术,测定胃癌患者癌组织及外周血中T淋巴细胞亚群、NK细胞水平,同时测定癌组织、癌周正常胃黏膜、淋巴结及外周血单个核细胞中4-1BB、4-1BBL含量。结果胃癌患者外周血中CD3^＋、CD4^＋、CD4^＋/CD8^＋比值和NK细胞表达水平均显著高于胃癌组织（P〈0.05）,CD8^＋细胞计数反之（P〈0.05）。4-1BB表达量由低到高的顺序为外周血单个核细胞、正常胃黏膜、淋巴结、癌组织、癌组织中单个核细胞;其中癌组织明显高于正常黏膜（P〈0.05）,有统计学意义;外周血单个核细胞中4-1BB表达量明显低于其他组织,有统计学意义（P〈0.01）。癌组织中4-1BBL表达量低于正常黏膜,有统计学意义（P〈0.05）。癌组织中4-1BB表达量与CD4^＋/CD8^＋比值、NK细胞表达水平呈负相关关系,4-1BBL与CD4^＋/CD8^＋比值、NK细胞表达水平呈正相关关系,有统计学意义（P〈0.05）。结论胃癌组织内免疫力低下,处于免疫抑制状态,胃癌组织的低免疫状态与4-1BBL缺乏有关;4-1BB与胃癌患者局部和全身的免疫状态亦有密切关系。总之,胃癌组织中4-1BB/4-1BBL的表达失衡与胃癌的免疫逃逸、低免疫状态有关。     

The expression of variant exon v7–v8 CD44 antigen in relation to lymphatic metastasis of human breast cancer

The purpose of this prospective study was to evaluate the expression of CD44 splice variant epitopes in human breast cancer and their potential as prognostic indicators.Invasive breast cancer tissues obtained from 91 patients were examined for expression of the standard CD44 antigen and variant CD44 antigens (v5, v6, v7, v7–v8, and v8–v10) by immunohistochemical staining to investigate the relations of these antigens to clinicopathological factors and prognosis.The expression of standard CD44 antigen was detected in 54.9% of 91 patients with primary human breast cancer. The variant epitopes of CD44 examined, i.e., v5, v6, v7, v7–v8, and v8–v10, were expressed in 54.9%, 54.9%, 0%, 34.1%, and 0%, respectively. There was a significant difference in tumor size, lymph nodal status, and degree of lymphatic permeation between patients who were positive for exon v7–v8 and those negative for this variant (p < 0.01). Prognosis was also significantly worse in patients positive for CD44 v7–v8 than in those negative for this variant. However, multivariate analysis with the three prognostic indicators tumor size, lymph nodal status, and the degree of lymphatic invasion, has shown that the expression of CD44 v7–v8 antigen in breast carcinoma was not a significant independent prognostic factor and was closely dependent on lymphatic invasion and nodal status. Fourteen of 31 patients who were positive for CD44 v7–v8 experienced recurrences. The mode of recurrence was lymphatic metastasis in 10 out of these 14 patients. Breast cancer cells expressing v7–v8 CD44 antigen have an extremely high affinity for lymph nodes and lymphatic vessels, and are likely to metastasize to distant lymph nodes even at a very early stage in the progression of this disease. This suggests that not only the anatomical factors but also organ affinity plays an important role in the establishment of lymph nodal metastasis of breast cancer.     

Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice

Few experimental studies have been conducted to clarify the mechanism of development of metastasis in scirrhous carcinoma of the stomach. In the present study, we attempted to establish gastric carcinoma cell lines by incubation of cancer cells collected from the body fluids of patients with gastric cancer. At the same time, xenografting of these cells to nude mice was performed. It was found that, of the gastric carcinoma cell lines thus established, two cell lines, designated as HSC-44PE and HSC-58, formed s.c. tumors with a high infiltrative potential (often invading the lymphatics around the cancer tissue) when implanted. Metastasis to the lymph nodes and lungs was observed in 20-40% of all the animals, indicating that the two cell lines are also capable of metastasizing spontaneously. Through repeated selection, i.e., repeated cycles of removal, culture, and implantation of the HSC cancer cells from metastatic lesions, we obtained 5 subclones of HSC-44PE and HSC-58 (designated as m2509, m2615, m2792, m2917, and m2691), which, when implanted orthotopically, exhibited the following characteristics as compared to the parent cells: (1) a higher percentage take (survival), similar frequency of metastasis, shorter time to metastasis (less than 100 days), and consistent metastasizing potential; (2) a relatively high frequency of metastasis to lymph nodes, including distant metastasis to axillary lymph nodes; (3) the potential to cause occasional bloody ascites; (4) enhanced expression of dysadherin, CD44, and other molecules. This is the first report of cultured scirrhous gastric carcinoma cells showing the potential for spontaneous metastasis.