利用组织芯片技术研究胃癌及其癌前病变中Bax、p53、Survivin表达的关系及意义

Objective： To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods： Tissue microarray and immunohistochemistry were used in this study. Results： The positive rate of Bax protein in gastric cancer （17.7%, 17/96） was significantly lower than those in adjacent normal mucosa （51%）, intestinal metaplasia （69.2%） and dysplasia （75%）, P 〈 0.01. The positive rate of Survivin expression in gastric cancer （80.6%, 89/98） was significantly higher than that in adjacent normal mucosa （3.9%）, P 〈 0.01. The positive rates of Survivin expression in tumors with different organ metastases （in lymph node metastasis 86.2%, liver 100% and ovarian 100%） were statistically higher than in tumors without metastasis （64.3%）, P 〈 0.05. Bax expression was correlated with Survivin but not with rap53 that was closely related to Survivin expression （P 〈 0.05） in gastric cancer. Conclusion： The abnormal expressions of Bax, Survivin and rap53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis, and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.     

FHIT基因在结直肠癌中的表达及其与细胞凋亡抑制的相关性

Objective： To investigate the expression of fragile histidine triad （FHIT） protein in normal colorectal tissue, colorectal adenoma and colorectal cancer （CRC）, and to study the relationships between the expression of FHIT protein and the clinical pathology, the apoptosis-associated protein （Bcl-2, Bax, Survivin）, apoptosis in colorectal cancer. Methods： Tissue microarray （TMA） and immunohistochemistry SP were used to detect the expression of FHIT gene, Bcl-2, Bax and Survivin in 16 cases of the normal colorectal tissue, 16 cases of colorectal adenoma and 80 cases of the colorectal cancer. TUNEL was used to detect the apoptosis index （Al） in 80 cases of the colorectal cancer. Results： （1） The positive rates of FHIT gene expression in normal colorectal tissue, colorectal adenoma and adenocancer were 93.75%, 68.75% and 46.25% respectively. There were no significant differences in the relationships between the FHIT gene expression and histological types, the gender as well as the age （P〉0.05）. There were significant relationships between FHIT gene expression and lymph node metastasis, histological grades, Duke＇s system as well as the 5-year survival rate after operation. （2） The positive rates of Bax, Bcl-2 and Survivin in colorectal adenocancer were 72.50%, 51.25%, 77.50% respectively. The expression of FHIT gene was positively correlated with that of Bcl-2, Bax and Survivin. （3） The mean AI in FHIT negative tumors was significantly lower than that in FHIT positive tumors （P〈0.01）. Conclusion： FHIT gene may play a role in the oncogenesis and progression of colorectal cancer. The abnormal regulation of apoptosis may play an important role in the pathogenesis of colorectal cancer.     

Down-regulated expressions of PPARγ and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren＇s classification in gastric carcinoma

Objective： To explore the relationship between peroxisome proliferator activated receptor-gamma （PPARγ） and peroxisome proliferator-activated receptor-gamma coactivator-1 （PGC-1） expression in gastric carcinoma （GC）, and analyze their correlations with clinicopathological features and clinical outcomes of patients. Methods：The two-step immunohistochemical method was used to detect the expression of PPARγ and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting. Results： The positive rates of PPART and PGC-1 expression were significantly lower in GC （54.75%, 49.16%） than in normal gastric mucosa （70.37%, 71.30%）, respectively （P〈0.05）. The decreased expression of PGC-1 in GC was confirmed ha our Western blot analysis （P=0.004）. PPAR7 and PGC-1 expressions were related to Lauren＇s types ofGC （P〈0.05）. Positive correlation was found between PPART and PGC-1 expression in GC （rk=0.422, P〈0.001）. The survival time of PPART negative and positive patients was 36.6±3.0 vs. 38.5_＋2.7 months, and no statistical difference was found between the 5-year survival rates of two groups （34.4% vs. 44.1%, P=0.522, log-rank test）; the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups （32.0% vs. 48.2%, P=0.462, log-rank test） Conclusions＇. Decreased expression of PPARγand PGC-1 in GC was related to the Lauren＇s classification. Their expressions in GC were positively correlated, indicating that their fimctions in gastric carcinogenesis may be closely related.     

免疫组化检测Survivin和Livin表达可预测Dukes'''' B期结直肠癌术后的复发和生存

Objective： To detect the expressions of Survivin and Livin in Dukes＇ B colorectal cancer tissues and analyze the prognosis after curative resection. Methods： The expressions of Survivin and Livin were evaluated immunohistochemically in Dukes＇ B colorectal cancer specimens from 81 patients after curative resection of the tumor. Their correlations to clinical characters and survival were also explored. Results： The positive rates of Survivin and Livin in colorectal cancer tissues were significantly higher than those in normal colorectal tissues （58.0% vs. 16.7% and 45.7% vs. 8.3% respectively, P 〈 0.05）. The expressions of Survivin and Livin were not related to gender, tumor site, primary size, T stage, pathologic category, and degree of differentiation （P 〉 0.05）, and no relationship was found between the expressions of Survivin and Livin （P 〉 0.05）. The expression rate of Survivin in patients older than 50 years was higher than that in patients younger than 50 years （70.6% vs. 36.7%, P 〈 0.05）. Both Survivin and Livin were related to recurrence and/or metastasis （P = 0.02 and P = 0.001, respectively）, and shorter survival （P = 0.039 and P = 0.001, respectively）. Cox multivariate analysis showed T4 and positive Livin expression were independent prognostic factors （P = 0.002 and P = 0.047, respectively）. Conclusion： Survivin and Livin are over-expressed in Dukes＇ B colorectal cancer tissues and are positively related to recurrence and/or metastasis and poor prognosis after curative resection of the tumor.     

Prognostic value of post-treatment 18F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy简

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.     

活检组织端粒酶活性检测评价肝癌合并肝硬化腹腔镜射频消融治疗的疗效

Objective： To explore the role of telomerase activity detected in biopsy samples for evaluating the efficacy of laparoscopic radiofrequency ablation （RFA） therapy in patients with hepatocellular carcinoma （HCC） and liver cirrhosis. Methods： From August 2001 to October 2004, 34 cirrhotic patients with HCC were treated by laparoscopic RFA under general anesthesia. A total of 34 tumors, with a mean maximum tumor diameter of 4.0 ＋ 1.0 cm, were all located on the liver surface or adjacent to the gallbladder. Laparoscopic ultrasound-guided core biopsy for liver lesions was performed before and immediately after RFA therapy. In these biopsy samples, telomerase activity was detected by the ELISA-based telomeric repeat amplification protocol （ELISA-TRAP） assay, and pathological examination was routinely performed. Results： Laparoscopic RFA was successfully performed in all the 34 patients. A complete tumor necrosis was achieved in all patients on the contrast-enhanced helical CT scanning one month after laparoscopic RFA. The positive rates of telomerase activity and histopathologic diagnosis in biopsy samples were 91.2% （31/34） and 100% （34/34） respectively before RFA, and 26.5% （9/34） and 0% respectively after RFA. During a median follow-up period of 35 months （range, 18-51 months）, the rates of local tumor recurrence at the ablation sites in post-RFA telomerase-positive and negative patients were 88.9% （8/9） and 4% （1/25） respectively （P 〈 0.01）, and the rates of distant recurrence within the livers were 0% （0/9） and 12% （3/25） respectively （P 〉 0.05）. Conclusion： For cirrhotic patients with HCC treated by laparoscopic RFA, detection of telomerase activity in biopsy samples may be useful for evaluating the therapeutic efficacy of RFA and predicting postoperative local tumor recurrence.     

核转录因子-κB在胰腺癌中的表达及其与上皮细胞间质转化的关系

 Objective　To investigate the expression of NF-κB and epithelial-mesenchymal transition(EMT) related markers E-cadherin and Vimentin proteins in human pancreatic cancer tissues and its relation with the malignant features． Methods　The expression of NF-κB、E-cadherin and Vimentin proteins in 62 cases of pancreatic cancer tissues were detected by using immunohistochemistry and compared with the clinicopathological data of pancreatic cancer. Results　The positive expression rate of NF-κB was 81 ％ (50/62), Vimentin protein increased of expression was 61 ％ (38/62), and E-cadherin protein loss of expression was 55 ％ (34/62) in pancreatic cancer. The positive expression rate of NF-κB was significantly related with the lymph node metastasis (χ2=11.761, P ＜0.05), distant metastasis(χ2＝9.225, P ＜0.05), the absent expression of epithelial marker E-cadherin protein (r =0．352, P <0．05) and the positive expression of mesenchymal marker Vimentin protein (r =0．343, P <0．05), but there was no relation with the patients gender, age, tumor location, tumor type and tumor differentiation (P ＞0．05)． In addition, the significant correlation of E-cadherin expression loss and Vimentin expression with tumor lymph node metastasis and distant metastasis was found (χ2＝6.914, 4.984, 7.753, 5.144, P <0.05). Conclusion　The overexpression of NF-κB in pancreatic cancer may accelerate invasion and metastasis of pancreatic cancer through inducing EMT．     

Significance of combined detection of LunX mRNA and tumor markers in diagnosis of lung carcinoma简

Objective：To evaluate the significance of combined detection of LunX mRNA,carcinoembryonic antigen （CEA）,neuron-specific enolase （NSE）,and cytokeratin 21-1 fragment （CYFRA21-1） in clinical diagnosis of lung carcinoma.Methods：Based on the quantitative RT-PCR and chemiluminescence immunoassay,the expression levels of LunX mRNA,CEA,NSE,and CYFRA21-1 in 113 patients with lung carcinoma （case group） and 30 healthy participants （control group） were detected.Meantime,the sensitivity,specificity,and accuracy of the combination detection were also explored.Results：The positive rates of LunX mRNA in peripheral blood and CEA,NSE,and CYFRA21-1 in serum were significandy higher in case group than those in control group （x2=17.295,16.825,19.148,and 17.450; P＜0.05）.There was no statistical significance when positive rate of LunX mRNA was evaluated among different pathological types （x2=0.047,P＞0.05）.The positive rate of LunX mRNA in stage Ⅰ ＋ Ⅱ,Ⅲ,and Ⅳ had a significandy increasing tendency （x2=10.565,32.462,P＜0.05）.The positive rate of CYFRA21-1 was highest in squamous carcinoma （78.5％）,the positive rate of NSE was highest in small cell carcinoma （86.7％）,and the positive rate of CEA wag highest in lung adenocarcinoma （80.4％）.The sensitivity and accuracy of the combination detection were 91.1％ and 88.1％,respectively.Conclusions：The combined detection of LunX mRNA and tumor markers （TMs） including CEA,NSE,and CYFRA21-1 in peripheral blood is helpful to increase the diagnostic accuracy of lmg cancer.Also,it can inform the pathological typing of lung carcinoma.     

凋亡抑制蛋白survivin在骨肉瘤中的表达对其发生和预后的意义

目的研究survivin凋亡抑制蛋白在骨肉瘤中的表达.探讨其在骨肉瘤发生及其预后中的可能作用.方法用免疫组化SP方法检测survivin蛋白在39例骨肉瘤和19例骨软骨瘤中的表达情况,并检查骨肉瘤患者的远处转移情况.结果Survivin在骨肉瘤中的阳性率为56.4%(22/39),明显高于对照组骨软骨瘤15.7%(3/19)的阳性率(x2=3.612,P＜0.05).在26例伴有远处转移的骨肉瘤病例中,survivin阳性率为61.5%(16/26),显著高于不伴有远处转移的骨肉瘤病例的阳性率30.8%(4/13)(x2=3.172,P＜0.05).结论Survivin的表达升高与骨肉瘤的发生机制有关,可能与骨肉瘤的远处转移相关.     

Survivin基因在骨肉瘤中的表达及其与临床耐药的相关性研究

目的探讨Survivin基因在骨肉瘤中的表达及其与临床耐药的相关性。方法采用免疫组织化学S-P法检测凋亡抑制基因Survivin在骨肉瘤、骨软骨瘤和正常骨组织中的表达及P-糖蛋白在骨肉瘤中的表达。结果Survivin基因在骨肉瘤中的阳性表达率为65.71%,在骨软骨瘤和正常骨组织中未见表达;Survivin阳性表达与患者的年龄、性别及肿瘤部位无关,与Enneking外科分期及WHO组织学分型有相关性;P一糖蛋白阳性表达率分别为45.71%,Survivin的表达与P-糖蛋白表达密切相关。结论Survivin在骨肉瘤中呈高表达,与临床耐药密切相关,有望成为骨肉瘤靶向治疗的一个新靶点。     

Survivin基因在骨肉瘤中的表达及其与临床耐药的相关性研究(英文)

目的探讨 Survivin 基因在骨肉瘤中的表达及其与临床耐药的相关性。方法采用免疫组织化学 S-P 法检测凋亡抑制基因 Survivin 在骨肉瘤、骨软骨瘤和正常骨组织中的表达及 P-糖蛋白在骨肉瘤中的表达。结果 Survivin 基因在骨肉瘤中的阳性表达率为65.71%,在骨软骨瘤和正常骨组织中未见表达;Survivin 阳性表达与患者的年龄、性别及肿瘤部位无关,与 Enneking 外科分期及 WHO 组织学分型有相关性;P-糖蛋白阳性表达率分别为45.7l%,Survivin 的表达与P-糖蛋白表达密切相关。结论 Survivin 在骨肉瘤中呈高表达,与临床耐药密切相关,有望成为骨肉瘤靶向治疗的一个新靶点。     

骨肉瘤组织中Survivin基因表达及其与细胞周期蛋白D1表达的关系

目的 :探讨骨肉瘤中抗凋亡基因Survivin的表达状态及其与细胞周期蛋白D1(cyclinD1)表达的关系。方法 :采用原位杂交、免疫组织化学技术、DNA原位末端标记 (TUNEL)法检测 3 8例骨肉瘤、15例骨软骨瘤、5例正常骨组织中SurvivinmRNA表达及骨肉瘤组织中cyclinD1表达和细胞凋亡情况 ,比较SurvivinmRNA表达与骨肉瘤临床病理参数及cyclinD1表达的关系。结果 :SurvivinmRNA在正常骨和骨软骨瘤组织无明显表达 ,但显著表达于骨肉瘤中 65 8% ( 2 5 /3 8) ,其表达率与骨肉瘤组织学分级无关 ,与WHO分型及转移有关 ,P <0 0 5 ;骨肉瘤细胞凋亡指数(AI)均值为 8 3 % ( 0～ 17% ) ,Survivin阴性组AI值显著高于阳性组 ,P <0 0 1;骨肉瘤中cyclinD1过度表达 ( 71 1% ,2 7/3 8) ,其与Survivin表达正相关 ,rs=0 3 70 ,P <0 0 5。结论 :Survivin选择性表达于骨肉瘤组织 ,通过抑制细胞凋亡 ,并与cyclinD1协同作用参与骨肉瘤的发生发展 ,Sur vivin可能是评价骨肉瘤预后的重要参考指标     

Skp2 、p27 在骨肉瘤中的表达及其临床意义

 目的 探讨骨肉瘤中Skp2和p27蛋白的表达与患者临床病理和预后的关系以及两种蛋白之间的相关性。方法 用免疫组织化学SP法检测16例骨软骨瘤和48例骨肉瘤组织中Skp2和p27蛋白的表达情况。结果 Skp2蛋白在骨软骨瘤中的表达均为阴性，而在骨肉瘤中的表达阳性率为43．75％（21／48），后者的阳性率显著高于前者（P〈0．01）。Skp2蛋白表达与临床分期、肺转移及分化程度显著正相关（P〈0．05）。p27蛋白在骨软骨瘤、骨肉瘤中阳性率分别为81．25％（13／16）、47．92％（23／48），两者比较，差异有统计学意义（P〈0．05）。p27蛋白表达与临床分期、肺转移及分化程度呈负相关（P〈0．05）。Skp2蛋白在骨肉瘤中表达与p27蛋白呈负相关（P〈0．05）。结论 Skp2可能通过对细胞周期抑制因子p27蛋白的降解而参与骨肉瘤的发生、发展，联合检测Skp2及p27蛋白的表达对骨肉瘤患者的早期诊断，判定恶性程度及预后具有指导意义。     

乳腺癌组织Survivin表达与细胞增殖的关系

目的:探讨乳腺癌组织中Survivin表达的临床病理学意义及其与癌细胞增殖的关系.方法:应用免疫组织化学SP法检测Survivin、Ki-67蛋白在96例乳腺癌组织中及20例正常乳腺组织的表达,分析Survivin 表达与Ki-67增殖指数及各临床病理因素的关系.结果:Survivin阳性表达乳腺癌的Ki-67增殖指数(35.32±21.28%)明显高于Survivin阴性者(20.42±11.34%),Survivin表达与肿瘤细胞增殖呈正相关(P<0.01);Survivin在乳腺癌组织中的表达率为70.83%(68/96),正常乳腺组织未见Survivin表达;Survivin蛋白的表达与临床分期、淋巴结转移和5年生存率有关(P<0.05),与年龄、是否绝经、肿瘤大小和组织学分级均无关.结论: Survivin不仅参与凋亡的调控,还促进细胞增殖. Survivin蛋白在乳腺癌中表达上调,提示其通过抑制凋亡在乳腺癌发生、发展中起重要作用,过度表达提示预后不良.     

叉头框蛋白M1在骨肉瘤组织中的表达及其与预后的相关性

目的:探讨骨肉瘤组织中叉头框蛋白M1(forkhead box protein M1，FOXM1)的表达及其与预后的相关性。 方法:采用免疫组化SP法分别检测FOXM1在96例骨肉瘤组织和30例骨软骨瘤组织中的表达；分析FOXM1表达情况与骨肉瘤临床病理特征的关系；采用Log-Rank检验及Cox回归分析FOXM1与骨肉瘤患者预后的相关性，并通过Kaplan-Meier法绘制生存曲线。 结果:骨肉瘤组FOXM1高表达率高于对照组(P<0.05)；骨肉瘤组织中FOXM1高表达与肿瘤临床分期和肺部转移相关(P<0.05)；单因素分析显示，FOXM1蛋白高表达、肺部是否转移、临床分期是影响生存预后的独立因素(P<0.05)；FOXM1蛋白高表达组的5年生存率为65.15%，低于低表达或无表达组的86.67%，差异有统计学意义(P<0.05)；多因素分析显示，FOXM1蛋白高表达、临床分期和肺部转移是影响骨肉瘤患者生存预后的独立危险因素(P<0.05)。 结论:FOXM1蛋白在骨肉瘤组织中高表达，与患者的肺部转移及临床分期等病理特征有关，且高表达与较差预后相关。     

p53基因在骨肉瘤中的表达及其临床意义

目的:探讨p53基因在骨肉瘤组织中的表达及其临床意义。方法:应用免疫组化方法(S-P法)测定p53蛋白在36例骨肉瘤和17例骨软骨瘤组织中的表达,并随访骨肉瘤患者生存时间。36例骨肉瘤中男19例,女17例,年龄平均19.9岁。Ennek ing分期Ⅱa3例,Ⅱb27例,Ⅲb6例,并发病理性骨折7例。结果:36例骨肉瘤随访时间平均3年6个月,其中存活3年及以上者13例,存活3年以下者23例,死亡病例均因骨肉瘤远处转移全身衰竭致死。36例骨肉瘤p53蛋白阳性表达率为52.8%,显著高于骨软骨瘤组,有显著性差异(P<0.01)。p53蛋白表达在不同Ennek ing外科分期组间无显著性差异(P>0.05),在生存时间3年以上组及3年以下组间有显著性差异(P<0.01)。结论:p53基因突变对骨肉瘤的发病可能产生影响,对患者预后评估具有一定价值。     

乳腺癌组织Survivin表达与细胞增殖的关系

目的：探讨乳腺癌组织中Survivin表达的临床病理学意义及其与癌细胞增殖的关系。方法：应用免疫组织化学SP法检测Survivin、Ki-67蛋白在96例乳腺癌组织中及20例正常乳腺组织的表达,分析Survivin表达与Ki-67增殖指数及各临床病理因素的关系。结果：Survivin阳性表达乳腺癌的Ki-67增殖指数（35．32±21．28％）明显高于Survivin阴性者（20．42±11．34％）,Survivin表达与肿瘤细胞增殖呈正相关（P〈0．01）;Survivin在乳腺癌组织中的表达率为70．83％（68／96）,正常乳腺组织未见Survivin表达;Survivin蛋白的表达与临床分期、淋巴结转移和5年生存率有关（P〈0．05）,与年龄、是否绝经、肿瘤大小和组织学分级均无关。结论：Survivin不仅参与凋亡的调控,还促进细胞增殖。Survivin蛋白在乳腺癌中表达上调,提示其通过抑制凋亡在乳腺癌发生、发展中起重要作用,过度表达提示预后不良。     

CXCR7在骨肉瘤组织中的表达及其临床意义

目的：探讨趋化因子受体7（CXCR7）在骨肉瘤组织中的表达及其与临床病理特征之间的关系。方法：采用免疫组化检测48例骨肉瘤组织标本、10例骨软骨瘤组织中 CXCR7的表达,分析其表达与患者临床病理参数之间的关系。结果：CXCR7在骨肉瘤组织和骨软骨瘤组织的阳性表达率是分别为75％和20％,差异具有统计学意义。CXCR7的表达与临床分期、有无转移密切相关（P ＜0．05）,与性别、年龄及肿瘤分化程度无明显关系（P ＞0．05）。结论：CXCR7在介导骨肉瘤侵袭及转移过程中可能起重要作用,有望作为骨肉瘤治疗的分子靶点。