B7-H1 与B7-H4 在膀胱癌大鼠及其癌旁组织中的差异表达

目的:研究膀胱原位癌组织及癌旁组织中共刺激分子 B7-H1与 B7-H4的表达情况,并分析二者的相关性。方法:采用 N-亚硝基 -N-甲基脲(MNU)溶液膀胱灌注法制备膀胱癌大鼠模型(30只),处死大鼠,获取癌组织及癌旁组织,进行病理检查;采用生理盐水溶液膀胱灌注法作为对照组( 12只),处死大鼠,获取膀胱组织,进行病理学检查;采用 RT-PCR技术分别检测对照组大鼠膀胱组织( A组)、膀胱癌模型组癌组织( B组)及模型组癌旁组织( C组)中 B7-H1与 B7-H4的 mRNA的表达水平,并分析二者之间的相关性。结果: 30只膀胱癌模型组大鼠, 28只模型制备成功,造模成功率 93.3%。A组、C组 B7-H1、B7-H4 mRNA表达量均明显低于 B组(0.71±0.38、0.79±0.21 vs 1.44±0.67;0.84±0.22、     

共刺激分子B7-H3 mRNA和B7-H3蛋白在胃癌组织中的表达及其临床意义

目的研究B7家族的新成员B7-H3mRNA和B7-H3蛋白在胃癌组织中的表达及其临床意义。方法采用荧光实时定量逆转录-多聚酶链反应（RT—PCR）方法检测38例胃癌患者癌组织及其邻近正常组织B7-H3mRNA的表达；免疫组织化学Elivision法检测B7．H3蛋白在胃癌组织中的表达。结果B7-H3mRNA在胃癌组织及其邻近正常组织中均有表达，其在胃癌组织中的表达明显低于邻近正常组织。B7-H3mRNA的表达与胃癌患者性别、年龄、组织类型、肿瘤大小、淋巴结转移、病理分级和浸润深度无关（P〉0.05）。B7-H3蛋白在胃癌组织中表达的阳性率为39、5％，其与患者性别、年龄、组织类型、肿瘤大小、淋巴结转移和浸润深度也无关（P〉0.05）。B7-H3蛋白表达随肿瘤临床分期的递增而降低，各组间差异有统计学意义（P=0.022）；病理分级各组间差异也有统计学意义（P=0.039）。Kaplan—Meier生存分析显示，B7-H3阳性表达组无病生存期明显优于B7-H3阴性表达组（P=0.009），B7-H3阳性表达组总生存期亦明显优于B7-H3阴性表达组（P=0.010）。结论B7-H3表达与胃癌预后有关，可以作为反映患者免疫状态和预后的一个新的指标．为制定临床治疗方案提供依据。     

胸苷激酶1和B7-H4在乳腺癌组织中的表达及临床意义

目的 观察胸苷激酶1(TK1)和B7-H4在乳腺癌组织中的表达,探讨两者与乳腺癌临床病理特征的关系.方法 收集64例乳腺癌患者手术切除的癌组织和癌旁组织标本,应用免疫组织化学法检测以上组织石蜡切片中TK1和B7-H4的表达水平.结果 TK1在乳腺癌组织中表达率明显高于癌旁组织(84.38％比15.63％,P＜0.01),B7-H4在乳腺癌组织中表达率明显高于癌旁组织(75.00％比20.31％,P＜0.01);TK1表达水平与乳腺癌乳腺癌肿瘤大小、组织学分化程度、TNM分期和淋巴结转移明显相关(P＜0.05),B7-H4表达水平与乳腺癌组织学分化程度和TNM分期明显相关(P＜0.05).结论 乳腺癌组织中TK1和B7-H4呈高表达,提示两者在乳腺癌的发生发展中有重要意义.     

共刺激分子B7-H1和FasL在膀胱移行细胞癌免疫逃逸中的机制研究及临床意义

目的：探讨共刺激分子B7-H1和FasL在膀胱移行细胞癌免疫逃逸机制中的作用及其临床意义。方法：应用免疫组织化学方法检测50例膀胱移行细胞癌及10例正常膀胱组织中B7-H1和FasL的表达．并用计算机图象分析系统对其表达水平进行定量分析。结果：正常膀胱组织中B7-H1和FasL。均不表达;50例膀胱移行细胞癌中．B7-H1和FasL的阳性表达率分别为72％和70％。B7-H1的表达水平与膀胱移行细胞癌的病理分级、临床分期及复发密切相关（P〈0．05）：FasL的表达水平与膀胱移行细胞癌的病理分级、I晦床分期密切相关（P〈0．05）．但与复发无关。B7H1的表达水平与FasL的表达水平呈正相关（r=0．798,P=0．000）。结论：B7-H1和FasL与膀胱移行细胞癌的发生发展密切相关．在膀胱移行细胞癌免疫逃逸中发挥了重要作用。联合检测B7-H1和FasL可以作为了解膀胱移行细胞癌乍物学行为的参考指标,干预B7-H1及FasL信号将有望成为膀胱移行细胞癌免疫治疗的新策略。     

肾透明细胞癌组织中B7-H1的表达及其与预后的关系

目的探讨B7-H1在肾透明细胞癌组织中的表达及其与预后的关系。方法采用免疫组织化学方法检测132例肾透明细胞癌患者术后肿瘤标本中B7-H1的表达,单因素及多因素分析B7-H1的表达与预后的关系。结果 132例患者中,B7-H1阳性46例（34.85%）,其中无瘤生存26例,复发6例,死亡14例,至最后随访期限,疾病无进展生存期（PFS）为（32.29±12.56）个月,总生存期（OS）为（27.08±15.43）个月;阴性86例（65.15%）,其中无瘤生存79例,复发3例,死亡4例,PFS为（38.77±20.00）个月,OS为（37.02±20.00）个月,两者比较差异有统计学意义（P〈0.05）。单因素分析表明,B7-H1阳性表达与肿瘤大小、原发肿瘤分期、区域淋巴结转移、远处转移、临床分期、组织学分级呈显著正相关（均P〈0.05）,而与患者年龄、性别无相关性。多因素分析表明,在控制肿瘤大小、TNM分期、临床分期、组织学分级的影响后,B7-H1阳性表达具有更高的肿瘤特异性死亡率[危险因素（RR）3.918,95%可信区间（95%CI）1.305～11.765,P〈0.05]和复发率[RR4.486,95%CI1.404～14.333,P〈0.05]。结论 B7-H1阳性表达与肾透明细胞癌患者术后死亡率及复发率呈正相关,B7-H1是肾透明细胞癌的一个独立预后因素。     

肾透明细胞癌组织中B7-H3的表达及意义

目的 评价B7-H3在肾透明细胞癌组织中的表达及其与预后的关系.方法 采用免疫组化方法 检测154例肾透明细胞癌患者肿瘤标本中B7-H3的表达,分析其与患者临床病理因素以及术后生存时间之间的关系.结果 154例患者中,B7-H3阳性28例(18.18%),其中无瘤生存6例,复发7例,死亡15例,至最后随访日期,总生存期(OS)为(19.71±20.32)个月;B7-H3阴性126例(81.82%),其中无瘤生存119例,复发3例,死亡4例,OS为(33.47±18.32)个月,两者比较差异有统计学意义(P＜0.05).单因素分析表明,B7-H3阳性表达患者在肿瘤大小、原发肿瘤分期、区域淋巴结转移、远处转移、临床分期等方面较阴性表达患者有明显差异,B7-H3阳性表达患者术后生存时间较阴性表达患者明显缩短.结论 B7-H3的表达可能与肾透明细胞癌的转移和进展有关,可以作为肾透明细胞癌的一个独立预后因素.     

B7-H3在肾透明细胞癌组织中的表达及其临床意义

目的 本研究旨在探讨B7-H3在肾透明细胞癌发生发展中的作用,为临床诊断、治疗肾癌提供新的靶标.方法 应用免疫组织化学染色检测69例肾透明细胞癌患者手术标本中肾癌组织、瘤旁组织及远离肿瘤组织中B7-H3的表达并对其表达情况与患者年龄、性别、肿瘤大小、病理分期、淋巴结转移等进行相关分析.结果 B7-H3在肾透明细胞癌组织中弥漫性表达,定位在癌细胞胞膜以及血管内皮细胞胞浆中.①B7-H3在肾透明细胞癌组织血管内皮细胞、肾癌细胞、瘤旁肾组织以及远离肿瘤正常组织中阳性表达率分别为79.7%、75.4%、13.0%及0%;②B7-H3癌组织中的表达强度与患者年龄、性别、肿瘤大小、淋巴结转移无关;但表达强度高者病理分期较高(P<0.01).结论 B7-H3在肾透明细胞癌癌组织中确有高表达,而在瘤旁肾组织表达较低,远离肿瘤的正常肾组织无表达,并且其表达率与表达强度与肿瘤的病理分期密切相关,这表明B7-H3与肾透明细胞癌的发生发展有着重要的关系,有望成为进行肾癌免疫治疗和抗血管治疗的"共靶点".     

B7-H4在膀胱尿路上皮癌组织和血清中的表达及临床意义

目的了解膀胱尿路上皮癌组织及患者血清中B7-H4的表达情况及其临床意义。方法应用免疫组化方法检测49例膀胱尿路上皮癌患者组织中B7-H4的表达,ELISA检测45例患者外周血可溶性B7-H4(sB7-H4)的含量,分析癌组织和血清中B7-H4的表达水平及与患者临床病理指标的相关性。结果膀胱尿路上皮癌组织中B7-H4阳性表达率为49.0%(24/49),而正常膀胱组织中无B7-H4表达(P<0.05),其表达水平与患者的肿瘤TNM分期和组织学分级密切相关(P<0.05);膀胱尿路上皮癌患者血清中sB7-H4的浓度较正常人显著增高(P<0.05),高级别患者表达量显著高于低级别患者(P<0.05)。结论 B7-H4在膀胱尿路上皮癌中表达上调,在膀胱尿路上皮癌的发生、发展及免疫逃逸中发挥着重要作用,封闭肿瘤组织中的B7-H4有可能干预膀胱尿路上皮癌的复发与进展。     

协同刺激分子B7-H3与B7-H4联合效应对胃癌患者预后的影响

目的 探讨胃癌组织中协同刺激分子B7-H3和B7-H4的表达水平对胃癌患者预后的影响及其与临床病理特征的关系.方法 采用回顾性研究随访调查157例胃癌患者的相关临床资料;应用免疫组织化学染色法检测相关病理指标及胃癌患者手术标本中B7-H3、B7-H4的表达;胃癌患者不同临床特征与B7-H3、B7-H4表达水平的相关性采用x2检验,不同临床特征患者的无进展生存期(PFS)及总生存期(OS)的比较采用Kaplan-Meier法及Log-rank检验,拟合多因素Cox模型,用风险比(HR)及95％可信区间(CI)估计不同临床指标与复发和死亡结局的联系强度.结果 B7-H3、B7-H4表达水平与不同临床特征之间无明显相关;单因素生存分析显示年龄较大(＞60岁)、分期较晚、肿瘤较大(＞5 cm)、浸润较深(侵及深肌层)、远处转移及协同刺激分子B7-H4高表达等显著减少PFS及OS(P ＜0.05);多因素Cox模型分析提示,与Ⅰ期[5.58(95％ CI:1.27 ～24.58)]比较,Ⅳ期胃癌患者复发和死亡的HR分别为6.20(95％ CI:1.31 ～29.34);与肿瘤直径≤5 cm的患者[1.95(95％ CI:1.20 ～3.18)]比较,肿瘤直径＞5 cm的患者其为1.97(95％CI:1.19 ～3.25);相对于其他表达组,B7-H3低表达且B7-H4高表达的胃癌患者复发和死亡的HR分别为1.92(95％ CI:1.20 ～ 3.10),1.93(95％CI:1.19 ～3.10).结论 B7-H3、B7-H4不同表达水平对胃癌患者PFS和OS有显著影响.     

B7-H1与移植免疫

B7-homolog1（B7-H1）是迄今发现的B7家族中较新的共刺激分子。它对T细胞具有双重效应,可以激活初始T细胞,抑制活化的效应T细胞。参与多种免疫过程的发生。在一些动物器官移植模型研究中,发现B7-H1在抑制免疫排斥,诱导免疫耐受,保护移植物中有重要的作用。以B7-H1为靶点的干预方法在未来可能成为器官移植后免疫抑制治疗的有效方法。本文就B7-H1在移植免疫中作用的研究进展做一综述。     

B7-H1在直肠癌与镶嵌血管中的表达及意义

目的 探讨共刺激配体B7-H1在直肠癌和镶嵌血管中的表达及临床意义.方法 应用免疫组织化学方法 观察50例直肠癌患者癌组织和镶嵌血管中的B7-H1表达,探讨B7-H1表达和直肠癌的病理学特征及预后间的关系.结果 随访期13例患者死亡,37例存活患者的中位随访期为3.4年(0～5年);64%的标本显示蛋B7-H1阳性染色,中位染色评分为2.5(0～4);B7-H1阳性表达与临床和病理特征呈逆相关(P＜0.05).15例(30%)的肿瘤患者同时B7-H1和镶嵌血管表达阴性,3例(6%)B7-H1阴性而镶嵌血管阳性,13(26%)B7-H1阳性而镶嵌血管阴性,19例(38%)B7-H1和镶嵌血管同时阳性表达.B7-H1阳性的肿瘤患者较N7-H1阴性的患者更可能镶嵌血管表达阳性(59.3%比11.1%;P＜0.01).双阳性组的生存率明显低于阴性或单阳性组(P＜0.01).21例表达镶嵌血管的直肠癌标本中有8例显示镶嵌血管内的内皮细胞或肿瘤细胞存在B7-H1的表达.结论 在直肠癌及镶嵌血管中阳性表达的B7-H1可作为直肠癌患者的预后标志.B7-H1参与直肠癌及镶嵌血管的免疫逃逸.     

胰腺癌中磷酸酶和张力蛋白同源物基因及B7-H1蛋白的表达及其临床意义

目的 观察胰腺癌磷酸酶和张力蛋白同源物基因(PTEN)蛋白和B7-H1蛋白的表达,探讨两者与胰腺癌肿瘤生物学特征的关系.方法 采用免疫组织化学ELPS法检测43例胰腺癌患者的组织标本和作为对照的5例非癌胰腺标本中PTEN和B7-H1蛋白的表达水平,分析其与临床和病理学特征的关系.结果 比较非癌胰腺组织,胰腺癌组织中PTEN蛋白表达显著降低,而B7-H1蛋白表达显著升高(P＜0.01),两者的表达还呈现显著负相关(r=-0.414,P＜0.01);两者的表达水平与肿瘤的分化程度、TNM分期、浆膜侵犯及淋巴结转移有关(P＜0.05),B7-H1表达水平还与年龄显著相关(P＜0.01);两者分别的表达水平与患者的预后均显著相关(P＜0.01),两者的联合表达水平与患者的预后相关(P＜0.05).结论 mN和B7-H1蛋白的表达水平与胰腺癌的发生、发展和预后密切相关.

Abstract：

Objective To investigate the probable correlation between the expressions of phosphatase and tensin homologue deleted on chromosometen (PTEN) and B7-H1 protein in pancreatic carcinoma and the biological behavior characteristics of tumors. Methods Forty-three patients were recruited who had undergone surgical resection for pancreatic carcinoma between 2002 and 2009. The PTEN and B7-H1 protein expressions in the tissue specimens of these 43 patients and 5 non-pancreatic carcinoma people' s pancreatic tissue specimens were evaluated by immunohistochemistry ELPS technique, and the clinical and pathological features of these specimens and the follow-up information were analyzed. Results PTEN expressions were significantly lower in pancreatic carcinoma tissues than in non-pancreatic carcinoma people' s pancreatic tissues but B7-H1 expressions were significantly higher ( P ＜ 0. 01 ). The expression of PTEN was negatively correlated to that of B7-H1 (r = -0.414 ,P ＜0. 01). PTEN and B7-H1 expressions correlated with the pathological grade and tumor-node-metastasis ( TNM ) stage, peripancreatic invasion, regional lymph node involvement,respectively (P＜0. 05). B7-H1 expressions also significantly correlated with the ages (P＜0. 01). Furthermore, PTEN and B7-H1 expressions showed significant prognostic effects (P＜0.01) and there are correlations existed between combined PTEN/B7-H1 expression and prognostic effects (P ＜0. 05). Conclusion The expression of PTEN and B7-H1 may be significantly correlated to the carcinogenesis,development and prognosis of pancreatic carcinoma.     

胰腺癌中磷酸酶和张力蛋白同源物基因及B7-H1蛋白的表达及其临床意义

Objective To investigate the probable correlation between the expressions of phosphatase and tensin homologue deleted on chromosometen (PTEN) and B7-H1 protein in pancreatic carcinoma and the biological behavior characteristics of tumors. Methods Forty-three patients were recruited who had undergone surgical resection for pancreatic carcinoma between 2002 and 2009. The PTEN and B7-H1 protein expressions in the tissue specimens of these 43 patients and 5 non-pancreatic carcinoma people' s pancreatic tissue specimens were evaluated by immunohistochemistry ELPS technique, and the clinical and pathological features of these specimens and the follow-up information were analyzed. Results PTEN expressions were significantly lower in pancreatic carcinoma tissues than in non-pancreatic carcinoma people' s pancreatic tissues but B7-H1 expressions were significantly higher ( P ＜ 0. 01 ). The expression of PTEN was negatively correlated to that of B7-H1 (r = -0.414 ,P ＜0. 01). PTEN and B7-H1 expressions correlated with the pathological grade and tumor-node-metastasis ( TNM ) stage, peripancreatic invasion, regional lymph node involvement,respectively (P＜0. 05). B7-H1 expressions also significantly correlated with the ages (P＜0. 01). Furthermore, PTEN and B7-H1 expressions showed significant prognostic effects (P＜0.01) and there are correlations existed between combined PTEN/B7-H1 expression and prognostic effects (P ＜0. 05). Conclusion The expression of PTEN and B7-H1 may be significantly correlated to the carcinogenesis,development and prognosis of pancreatic carcinoma.     

胰腺癌中磷酸酶和张力蛋白同源物基因及B7-H1蛋白的表达及其临床意义

Objective To investigate the probable correlation between the expressions of phosphatase and tensin homologue deleted on chromosometen (PTEN) and B7-H1 protein in pancreatic carcinoma and the biological behavior characteristics of tumors. Methods Forty-three patients were recruited who had undergone surgical resection for pancreatic carcinoma between 2002 and 2009. The PTEN and B7-H1 protein expressions in the tissue specimens of these 43 patients and 5 non-pancreatic carcinoma people' s pancreatic tissue specimens were evaluated by immunohistochemistry ELPS technique, and the clinical and pathological features of these specimens and the follow-up information were analyzed. Results PTEN expressions were significantly lower in pancreatic carcinoma tissues than in non-pancreatic carcinoma people' s pancreatic tissues but B7-H1 expressions were significantly higher ( P ＜ 0. 01 ). The expression of PTEN was negatively correlated to that of B7-H1 (r = -0.414 ,P ＜0. 01). PTEN and B7-H1 expressions correlated with the pathological grade and tumor-node-metastasis ( TNM ) stage, peripancreatic invasion, regional lymph node involvement,respectively (P＜0. 05). B7-H1 expressions also significantly correlated with the ages (P＜0. 01). Furthermore, PTEN and B7-H1 expressions showed significant prognostic effects (P＜0.01) and there are correlations existed between combined PTEN/B7-H1 expression and prognostic effects (P ＜0. 05). Conclusion The expression of PTEN and B7-H1 may be significantly correlated to the carcinogenesis,development and prognosis of pancreatic carcinoma.     

共刺激分子B7-H4在胃癌组织中表达及其与预后的关系

H4的高表达与胃癌患者的生存时间成负相关,证实了B7-H4为一负性调节分子,可作为判断胃癌生存期的指标;CIK细胞治疗可以显著延长胃癌患者的生存期.     

肾移植患者血清中可溶性B7-H3水平的变化及其临床意义

Objective To detect the serum soluble B7-H3 (sB7-H3) in patients before and after renal transplantation, and to investigate the clinical significance. Methods The serum level of sB7-H3 in 34 patients were determined before and 3, 6, 12 months after renal transplantation. Besides, 11 health adults were elected as controls. These 34 patients were divided into two groups according to HLA and/or MICA antibodies using Luminex before operation. After transplantation, all the patients were divided into two groups according to their conditions; group Ⅰ with rejection; group S with stable renal function and no rejection. Results The serum level of sB7-H3 in all 34 patients before operation was significantly higher than health controls [(27. 10 ± 13. 61) μg/L,n = 34 vs (11.61 ±3.77) μg/L,n = 11 ,P ＜0. 01], and significantly higher in patients with antibodies than in those without before operation [(34. 96 ± 17. 37) (μ/L, n = 11 vs (23. 34 ± 9. 75) (μg/L, n = 23, P ＜ 0. 05]. There was no significant difference in the serum level of sB7-H3 between control group and S group after operation (P ＞0. 05). In group Ⅰ, the serum level of sB7-H3 was increased obviously when rejection occurred [(20. 63 ±4. 28) μg/L,n = 12; (18. 95 ±2.98) μg/L,n=6; (28.36 ±19. 83) μg/L,n = 10] , as compared with group S and control group (P＜0. 01), while at the time without rejection, there was no difference among them (P ＞0. 05). Conclusion Monitoring serum sB7-H3 after renal transplantation would be clinically useful in indicating therapeutic effect and outcome of the patients.     

肾移植患者血清中可溶性B7-H3水平的变化及其临床意义

Objective To detect the serum soluble B7-H3 (sB7-H3) in patients before and after renal transplantation, and to investigate the clinical significance. Methods The serum level of sB7-H3 in 34 patients were determined before and 3, 6, 12 months after renal transplantation. Besides, 11 health adults were elected as controls. These 34 patients were divided into two groups according to HLA and/or MICA antibodies using Luminex before operation. After transplantation, all the patients were divided into two groups according to their conditions; group Ⅰ with rejection; group S with stable renal function and no rejection. Results The serum level of sB7-H3 in all 34 patients before operation was significantly higher than health controls [(27. 10 ± 13. 61) μg/L,n = 34 vs (11.61 ±3.77) μg/L,n = 11 ,P ＜0. 01], and significantly higher in patients with antibodies than in those without before operation [(34. 96 ± 17. 37) (μ/L, n = 11 vs (23. 34 ± 9. 75) (μg/L, n = 23, P ＜ 0. 05]. There was no significant difference in the serum level of sB7-H3 between control group and S group after operation (P ＞0. 05). In group Ⅰ, the serum level of sB7-H3 was increased obviously when rejection occurred [(20. 63 ±4. 28) μg/L,n = 12; (18. 95 ±2.98) μg/L,n=6; (28.36 ±19. 83) μg/L,n = 10] , as compared with group S and control group (P＜0. 01), while at the time without rejection, there was no difference among them (P ＞0. 05). Conclusion Monitoring serum sB7-H3 after renal transplantation would be clinically useful in indicating therapeutic effect and outcome of the patients.