非小细胞肺癌中WWOX蛋白、Ki67的表达及其意义

目的 探讨WWOX(WW domain-containing oxidoreductase)基因在非小细胞肺癌(NSCLC)组织中的表达及其临床意义.方法 用免疫组化方法检测50例鳞癌,31例腺癌及20例癌旁正常组织中WWOX基因蛋白的表达,并分析其与各临床病理指标、细胞增殖之间的关系.结果 WWOX基因在72.8%的NSCLC中失表达或表达减少,而在相邻正常肺组织中有80.0%正常表达.WWOX基因的表达与组织类型、腺癌细胞分化程度密切相关(r=0.262,r=0.457,P＜0.05),在鳞癌和低分化腺癌中WWOX基因失表达或表达减少.细胞增殖指数越高,WWOX基因表达越少,二者呈负相关(r=-0.252,P＜0.05).Ki67的表达与吸烟、组织分化、临床分期、淋巴结转移密切相关(均P＜0.05);与WWOX蛋白表达呈负相关(r=-0.252,P＜0.05).结论 WWOX蛋白在NSCLC组织中呈低表达,其表达的缺失可能在不同类型NSCLC的形成中发挥了不同的作用,而且与肿瘤的恶性程度及侵袭有关.Ki67蛋白的高表达提示预后不佳.     

C-myc基因和P16基因在肝细胞癌中的表达及其临床意义

目的探讨C-myc基因和P16基因表达在肝细胞癌(HCC)中的临床意义。方法采用免疫组化检测技术检测不同肝癌组织、癌旁组织及正常肝组织中的C-myc基因和P16基因表达产物。结果C-myc基因表达产物在肝癌组织中的表达明显高于癌旁组织和正常肝组织(P<0.05)。P16基因表达产物则在正常肝组织中和癌旁组织中表达明显高于肝癌组织(P<0.05)。C-myc基因的表达与HCC的发病年龄、性别、肿瘤大小、UICC分期无关(P>0.05),而与HCC的转移有关(P<0.05);P16基因的表达与HCC的发病年龄、性别、肿瘤大小无关(P>0.05),而与HCC的转移和UICC分期有关(P<0.05)。结论C-myc基因表达增强与P16基因表达障碍能促进HCC的发生发展,并可用来判断预后。     

精氨酸酶1在肝细胞癌中的表达及其临床病理意义

目的 检测人类精氨酸酶1(ARG1)在肝细胞癌(HCC)中的表达,分析其与患者临床病理特征的关系.方法 利用高通量组织芯片技术和免疫组织化学方法评价167例HCC及癌旁肝组织中ARG1蛋白的表达情况,采用x2检验和Spearman秩相关分析ARG1蛋白表达与各临床病理特征间的关系.应用实时荧光定量PCR方法检测68例HCC及其癌旁肝组织中的ARG1 mRNA表达水平.结果 HCC中ARG1蛋白表达水平为3.540±3.702,明显低于癌旁肝组织(10.290±2.303;t=-22.421,P=0.000).ARG1表达与HCC分化程度、组织学分级、微血管侵犯、术前甲胎蛋白水平、术后复发有关(P值均＜0.05).68例HCC组织中ARG1 mRNA表达水平为0.0997(0.213),低于癌旁肝组织0.563(0.459);u=-6.544,P=0.000].结论 ARG1在HCC中低表达,其可能参与HCC发生发展.检测ARG1表达可能有助于HCC辅助诊断、评估分化程度及预后判断.     

肝癌中Bcl-2、Bax和C-myc基因的表达及其临床意义

目的 探讨Bcl-2、Bax和C-myc基因表达在肝细胞癌(HCC)中的临床意义.方法 采用免疫组化技术检测不同HCC组织、癌旁组织及正常肝组织中的Bcl-2、Bax和C-myc蛋白表达.结果 Bcl-2、Bax和C-myc在HCC组织、癌旁组织和正常肝组织中均有部分阳性表达;Bcl-2和C-myc蛋白在HCC组织中呈高表达,其个体阳性率明显高于正常肝组织(P＜0.05);Bax蛋白在HCC组织中呈低表达,其个体阳性率明显低于正常肝组织(P＜0.05);Bcl-2基因的表达与HCC的发病年龄、性别、肿瘤大小、UICC分期和转移均无关;Bax基因的表达与HCC的发病年龄、性别、肿瘤大小和转移无关(P＞0.05),而与HCC的UICC分期有关(P＜0.05);C-myc基因的表达与HCC的发病年龄、性别、肿瘤大小和UICC分期无关(P＞0.05),而与HCC的转移有关(P＜0.05).结论 Bcl-2、Bax和C-myc基因相互协调作用,促进HCC的发生和发展.     

Pokemon基因在原发性肝癌组织中的表达及意义

采用免疫组化PV-9000二步法检测 Pokemon蛋白在原发性肝癌(HCC)癌组织、癌旁组织及正常肝组织中的表达情况,分析其表达与HCC临床病理特征的关系.结果 Pokemon蛋白在癌组织中的阳性率(54%)明显高于癌旁组织(30%)、正常组织(10%),其表达与肿瘤大小有关(P＜0.05).提示Pokemon基因可促进HCC的发生、发展.     

生存蛋白和半胱天冬酶-8在肝癌中的表达及其临床意义

目的 研究生存蛋白（survivin,Surv）和半胱天冬酶8（caspase8,Casp8）在肝细胞癌（HCC）（肝癌）中的表达与细胞凋亡的关系.方法 应用免疫组化SP法检测42例肝癌、42例癌旁组织和12例正常肝组织石蜡切片中Surv和Casp8的表达情况.结果 Surv在正常肝组织中无表达,在癌旁组织和HCC中的表达率分别为7.14%和78.6%,二者差异显著（P＜0.01）.阳性表达细胞表现为细胞质内有棕黄色颗粒,核内无表达;Casp8在正常肝组织中、癌旁组织和HCC中的表达率分别为91.7%、85.7%、57.14%,其中HCC与前二者比较差异显著（P＜0.05）,而癌旁组织和正常组织比较无差异（P＞0.05）.阳性表达细胞表现为细胞质内有棕黄色颗粒;二者的表达与肿瘤组织学分级和转移密切相关.组织学分级越低以及有肝内外转移或转移倾向者,Surv表达率越高（P＜0.05）,而Casp8表达率越低（P＜0.05）.结论 Surv在HCC中稳定高效表达,可通过抑制Casp8活性而抑制细胞凋亡;Surv高表达和Casp8低表达可作为HCC独立的不良预后因子.     

非小细胞肺癌中WWOX蛋白的表达及意义

目的 研究抑癌基因WWOX在非小细胞肺癌中的蛋白表达及临床意义.方法 应用免疫组织化学二步法检测40例非小细胞肺癌石蜡标本及21例癌旁正常肺组织中WWOX蛋白的表达.结果 ①癌旁正常肺组织中WWOX蛋白阳性表达率高于非小细胞肺癌组织(85.71％ vs 37.50％,P＜0.05),鳞癌中WWOX蛋白阳性表达率与腺癌差异无统计学意义(34.62％ vs 42.86％,P＞0.05);②男性非小细胞肺癌患者癌组织中WWOX蛋白阳性表达率低于女性非小细胞肺癌患者(25.00％ vs56.25％,P＜0.05),吸烟指数≥400的患者癌组织中WWOX蛋白阳性表达率低于吸烟指数＜400的患 者(19.05％ vs 57.89％,P＜0.05),而WWOX蛋白呈阳性表达的患者年龄与阴性表达者之间差异无统计学意义(P＞0.05);③分化不良的非小细胞肺癌组织中WWOX蛋白阳性表达率与中等分化和分化良好者相近(P＞0.05);④Ⅰ+Ⅱ期非小细胞肺癌患者癌组织中WWOX蛋白阳性表达率与Ⅲ+Ⅳ期患者相比差异无统计学意义(P＞0.05),转移病例的非小细胞肺癌组织中WWOX蛋白阳性表达率与无转移病例相近(P＞0.05).结论 WWOX蛋白在非小细胞肺癌组织中表达较癌旁正常肺组织降低,且与患者性别及吸烟指数密切相关,而与年龄、病理类型、组织分化程度、临床分期以及有无转移无明显关系.     

MAGE-4基因在肝细胞肝癌中的表达及临床意义

目的通过研究MAGE-4基因在肝细胞肝癌组织中的表达,并与患者临床资料进行分析,探讨 MAGE-4基因与肝细胞肝癌(HCC)患者临床指标及转移与复发的关系,为MAGE-4基因编码蛋白用于HCC患者免疫治疗提供依据. 方法用RT-PCR的方法对31例HCC患者癌组织及相应癌旁组织MAGE-4基因表达进行测定,对全部RT-PCR扩增产物中目的基因片段进行DNA测序以证实其为 MAGE-4基因,患者均测定并统计AFP、AFU、抗HCV、HBsAg、AFP mRNA、肿瘤直径等临床指标. 结果 31例HCC患者肝癌组织中MAGE-4基因表达的阳性率38.7% (12/31)明显高于癌旁组织中MAGE-4基因表达的阳性率0% (0/31),P＜0.01.HCC患者肝癌组织中MAGE-4基因表达的阳性率与患者AFP、AFU、抗HCV、HBV标志物、AFP mRNA、肿瘤直径等临床指标均无关,P＞0.05. 结论 MAGE-4基因在HCC患者肝癌组织中特异高表达,可能作为HCC患者免疫治疗攻击的靶点,HCC患者肝癌组织中 MAGE-4基因表达的阳性率与HCC患者肿瘤标志物、转移、复发均无关.     

Expression of histone deacetylase 1 and matrix metalloproteinase -2 in hepatoceilular carcinoma and its significance

目的 探讨组蛋白去乙酰化酶1( HDAC1)及基质金属蛋白酶-2(MMP -2)在肝细胞癌(HCC)患者肝组织中的表达及其临床意义.方法 采用免疫组织化学方法检测42例HCC和相应的癌旁组织中HDAC1及MMP -2蛋白的表达,并分析其与临床病理参数的关系.结果 HCC组织中,HDAC1及MMP -2蛋白的表达明显高于癌旁组织(P＜0.01,P＜0.05);HDAC1蛋白的表达与患者性别、年龄、肿瘤大小、AFP浓度、肿瘤分化程度、脉管癌栓无关联(P＞0.05),与肿瘤TNM分期相关联(P＜0.05);MMP -2蛋白的表达与患者性别、年龄、肿瘤大小、AFP浓度、肿瘤分化程度无关联(P＞0.05),与脉管癌栓、肿瘤TNM分期相关联(P＜0.05,P＜0.01 );HCC组织中,HDAC1及MMP -2蛋白的表达呈正相关(P＜0.01).结论 HDAC1及MMP -2在HCC患者肝组织中表达有一定的肿瘤特异性,二者的高表达提示HCC已属晚期.     

胃癌组织中FHIT蛋白的表达及意义

应用免疫组织化学SP法检测53例胃癌组织及14例癌旁组织中FHIT的表达.结果 胃癌组织FHIT蛋白阳性表达率(49.1%)显著低于癌旁组织(92.2%)(P＜0.05);53例胃癌组织中,高中分化组(54.8%)与低分化组间(40.9%),淋巴结转移组(44.7%)与无淋巴结转移组间(60.0%),Ⅰ Ⅱ期组(57.9%)与Ⅲ Ⅳ期组间(44.1%)FHIT蛋白阳性表达率差异均有统计学意义(P均＜0.05).认为FHIT基因与胃癌的发生、发展有关,FHIT蛋白可作为判定胃癌发生及转移能力的指标之一.     

FADD and TRADD expression and apoptosis in primary hepatocellular carcinoma

AIM To investigate the clinical features of FADD and TRADD expressions in primary hepatocellular carcinoma ( HCC ) and to determine their relationship with hepatic apoptosis. METHODS FADD and TRADD expressions were detected by immunohistochemistry and hepatic apoptosis were determined by in situ endlabeling ( ISEL). RESULTS Ten (25.6%) cases of HCC were detected to express FADD protein. The positive rate in HCC is lower than that in non-cancerous adjacent liver tissues (62.5%) (P＜0.05). In those of grade Ⅰ - Ⅱ, 8 (38.1%) cases were FADD positive, while only 2/18 (11. 1%) cases of grade Ⅲ - Ⅳ had detectable FADD protein (P＜0.05). No relationship was found between FADD expression and other clinical features,such as gender, age, tumor size, differentiation or metastasis. ISEL positive cells can be seen in all cases of HCC. The hepatic apoptosis was associated with FADD expression as more apoptotic cells were detected in those cases which had moderately to strongly positive FADD, as compared with negative or weak positive FADD cases (P＜ 0.05). No relationship was found between FADD expression and hepatic apoptosis in non-cancerous adjacent liver tissues. Fifteen of 39 (38.5%) cases of HCC were found positive for TRADD protein, and similar positive rate (37.5%) in non-cancerous adjacent liver tissues (P ＞0.05). The expression of TRADD is correlated with HCC differentiation,as only 22.2% of moderately to highly differentiated HCC showed positive TRADD protein, while as high as 52.4% of poorly differentiated HCC had TRADD (P＜0.05). No relationship was found between TRADD expression and gender, age, tumor size or grade or metastasis, although 42.9% of HCC of grade Ⅰ/Ⅱ showed positive TRADD which was slightly higher than that of grade Ⅲ/Ⅳ (33.3%,P ＞ 0.05). Hepatic apoptosis was not related to TRADD expression in HCC or non-cancerous adjacent liver tissues. CONCLUSION Loss of FADD expression plays an important role in HCC carcinogenesis, and expression of TRADD also contributes to HCC development. The cell apoptosis in HCC is associated with FADD expression. However, the expression of TRADD does not correlate well with hepatic apoptosis in HCC.     

Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis

AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor, and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC). METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001 and 2003. FHIT and proliferating cell nuclear antigen (PCNA) expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections. RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P= 0.001). The proportion of reduced FHIT expression in those carcinomas at stages Ⅲ-Ⅳ (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages HI (30.8%, P= 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P=0.030) and in those with negative FHIT expression (P=0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P= 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage, FHIT expression and metastasis. CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-prdiferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.     

骨桥蛋白下游信号分子在肝细胞癌中的表达

目的 通过肝癌组织芯片检测骨桥蛋白(OPN)下游的信号蛋白,以确定其在肝癌组织中的信号传导途径.方法构建肝细胞癌组织芯片,用免疫组织化学染色法检测并分析OPN及其相关分子、整合素αV、CD44v6、磷酸化黏着斑激酶(p-FAK)、p-Src、磷酸化细胞外信号调节激酶(p-ERK)、磷酸化蛋白激酶B(p-AKT)的表达水平及其关系.计数资料用卡方检验(或Fisher's确切概率法),各指标之间的相关性采用Spearman相关分析.结果OPN及其受体整合素αV、CD44v6和相关信号分子p-FAK、p-Src、Src、p-ERK、p-AKT在肝癌组织的表达水平均明显高于癌周正常肝组织(P＜0.05).FAK在肝癌和癌周组织中的表达差异无统计学意义(P＞0.05).OPN的表达与整合素oV(P＜0.01)、p-ERK(P＜0.01)、CD44v6(P＜0.05)密切相关,与p-FAK、p-Src、p-AKT无相关性(P＞0.05).但p-FAK(P＜0.05)、p-Src(P＜0.01)和p-AKT(P＜0.05)均与OPN受体整合素αV密切相关,p-FAK还与OPN的受体CD44v6密切相关(P＜0.01).结论 OPN通过其受体整合素αV、CD44v6激活下游的丝裂原活化蛋白激酶途径以促进肝癌转移.

Abstract：

Objective Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. Methods The expressions of OPN, intergrin α V, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis. The relationship of OPN with P-ERK, P-Src and P-AKT were explored and the role in HCC metastasis was analysed. Results The expression levels of OPN, intergrin α V, CD44v6, P-FAK, P-Src, Src, P-ERK and P-AKT in HCC tissue were significantly higher than that in normal tissue (P ＜ 0.05). No significant difference was found between the expression levels of FAK in HCC tissue and normal tissue (P ＞0.05). OPN expression was significantly associated with Integrin α v (P ＜ 0.01 ), CD44V6 (P ＜ 0.01) and P-ERK (P ＜ 0.05) but not with P-Stc, P-FAK and P-AKT (P ＞ 0.05). The expressions of P-FAK (P ＜ 0.05), P-Src (P ＜ 0.01) and P-AKT (P ＜ 0.05) were significantly associated with Integrin α v and the P-FAK expression was also significantly associated with CD44V6 (P ＜ 0.01). Conclusion OPN promotes HCC metastasis though Integrin α v/CD44V6/MAPK pathway in human HCC.     

蛋白酶激活受体1在癌旁组织中的高表达与肝癌早期患者术后预后不良相关

目的 研究蛋白酶激活受体1(PAR1)在肝细胞肝癌(HCC)及癌旁组织的表达水平,探讨其与HCC早期患者预后的相关性.方法 应用实时定量聚合酶链反应检测随机选择的41例经根治性切除的HCC早期患者癌组织及对应的癌旁组织中PAR1的mRNA表达水平,并分析其与肝细胞肝癌预后的相关性.另随机选择49例H C C早期患者组织石蜡切片做免疫组织化学染色,分析其与HCC临床病理特征及预后的相关性.计数资料比较采用卡方或Fisher精确概率法;计量资料比较用两组间比较的t检验或Wilcoxon符号秩检验;生存率的判定使用Kaplan-Meier方法,差异性使用Log-rank检验评估.结果 癌旁组织中,复发组的PAR1 mRNA表达水平明显高于非复发组(0.591±0.458比0.361±0.177,T=-2.379,P＜0.05).PAR1蛋白在癌旁组织的表达水平与肿瘤分化程度相关(P＜0.05).PAR1阳性组患者生存时间为(58.39±4.59)个月,1、3、5年累计生存率分别为90.3%、83.9%和61.8%; PAR1阴性组患者生存时间为(75.84±1.87)个月,1、3、5年累计生存率分别为100.0%、100.0%和94.1%.PAR1阳性组患者至复发时间为(51.97±4.30)个月,1、3、5年累计复发率分别为10.2%、25.2%和40.6%;阴性组患者至复发时间为(71.92±3.77)个月,1、3、5年累计复发率分别为0、5.6%和21.3%.癌旁组织PAR1蛋白阳性表达组1、3、5年总生存率明显低于阴性表达组(x2=5.297,P＜0.05),累计复发率明显高于阴性表达组(x2=4.682,P＜0.05).结论 PAR1在HCC早期患者癌旁组织中的表达与术后患者的预后密切相关,其可能参与了凝血酶介导的肝细胞肝癌的恶性侵袭行为,并可能成为判断预后的预测指标.

Abstract：

Objective To evaluate the relationship between PAR1 (Protease-Activated Receptor 1)expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection. Methods Real-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage.Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated. Results Peritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P＜0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P＜0.05). KaplanMeier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival(OS) (P＜0.05) of HCC patients and the time to recurrence (TTR) (P＜0.05). The 1,3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue. Conclusion Peritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.     

肿瘤拒绝抗原1在肝硬化和肝癌组织中的表达及其与肝癌临床病理学特征的关系

目的 探讨肿瘤拒绝抗原1(TRA1)在肝细胞癌(HCC)和肝硬化组织中的表达水平及其与HCC临床病理学特征的关系.方法 采用RT-PCR法、Western blot和免疫组织化学法分别检测了HCC和肝硬化组织中TRA1 mRNA和蛋白的表达水平,并与HCC临床病理学特征进行相关分析.RT-PCR和Western blot结果采用单因素方差分析;免疫组织化学结果分析采用Fisher's确切概率法;相关性分析采用Spearman等级相关.结果 经对RT-PCR结果分析,HCC和肝硬化组织中TRA1 mRNA表达水平高于正常肝组织水平(F值分别为20.821和12.311,P值均＜0.05).Western blot检测结果显示,HCC和肝硬化组织中TRA1蛋白表达水平也高于正常肝组织(F值分别为21.231和20.125,P值均＜0.05).经免疫组织化学分析,TRA1蛋白在正常对照组、肝硬化组和HCC组的表达逐渐增强,阳性表达率分别为57.14%、78.95%和93.75%.其表达水平与HCC分化程度呈负相关(r=-0.4655,P＜0.01);与HCC患者TNM分期呈正相关(r=0.5157,P＜0.01).结论 TRA1在肝硬化和HCC中的过表达可能与肝癌的发生和发展有关,并有可能成为一个潜在的HCC早期诊断标志物;TRA1的检测有助于判断HCC的分化程度,与HBV的感染有一定关系,同时可作为判断预后的指标.     

Cigarette smoking extract causes hypermethylation and inactivation of WWOX gene in T-24 human bladder cancer cells

Genomic, epigenetic and expression alterations of WW domain containing oxidoreductase (WWOX) have been implicated in multiple tumor types. The current study was designed to examine the expression of WWOX in tumor tissues of human bladder transitional cell carcinoma (BTCC) and the influence of cigarette smoke extract (CSE) on WWOX expression and methylation status in T-24 bladder cancer cells. WWOX protein expression was evaluated by immunohistochemistry staining in a series of tumor samples from 78 patients with BTCC and 26 normal bladder tissues. The expression level and methylation status of WWOX in CSE-treated cells were examined by using quantitative Real-Time RT-PCR and methylation specific PCR, respectively. The expression levels of DNA methyltransferases (DNMTs) 1, 3A and 3B were also detected. We found that WWOX expression was absent or reduced in 79.5% (62/78) of BTCC tissues, but only in 19.2% (5/26) of normal bladder tissues. Loss of WWOX expression was correlated with tumor grade (P=0.019) and cigarette smoking (P=0.031), but was not associated with age, gender, tumor size and tumor number. Hypermethylation of WWOX promoter and exon 1 was specifically induced by CSE with a kinetics concurrent to the suppression of WWOX mRNA in T-24 cells. Furthermore, CSE treatment induced a significant time-dependent increase in the level of DNMT1, but has no effects on DNMT3A and DNMT3B. Taken together, these novel findings suggest that hypermethylation of WWOX induced by cigarette smoking may represent one underlying mechanism for the loss expression of WWOX in bladder cancer.     

Expression of transforming growth factor-α and hepatitis B surface antigen in human hepatocellular carcinoma tissues and its significance

AIM: To evaluate the expression of transforming growth factor-alpha (TGF-α) and hepatitis B surface antigen (HBsAg) in human hepatocellular carcinoma (HCC) tissues and its significance. METHODS: Seventy specimens of HCC tissues were detected by immunohistochemical method. Five specimens of normal human liver tissues were used as control. RESULTS: The TGF-α positive expression rates in HCC and its surrounding tissues were 74.3%(52/70) and 88. t%(52/59), respectively. TGF-α positive granules were mainly in the cytoplasm and fewer existed on the karyotheca. The TGF-α positive expressing rate in well differentiated HCC was significantly higher than that in moderately and poorly differentiated HCC (P＜0.05). The TGF-α positive expression also was observed in intrahepatic bile ducts (part of those were hyperplastic ducts). The HBsAg positive expression rates in HCC and its surrounding tissues were 21.4%(15/70) and 79.7%(47/59), respectively. HBsAg positive granules were in the cytoplasm, inclusion and on the karyotheca. There was a prominent positive correlation between TGF-α and HBsAg expression in HCC surrounding tissues (P＜0.05, γ=0.34). TGF-α was usually existed with HBsAg in regenerated and/or dysplastic liver cells. In the five normal liver tissues, TGF-α and HBsAg were not detectable in hepatocytes and bile ducts.CONCLUSION: Hepatitis B virus infection is closely related with hepatocarcinogenesis. The overexpression of TGF-α in the liver seems to be associated with the regeneration of hepatocytes injured by HBsAg. The continued expression of TGF-α might lead to dysplasia of liver cells and development of HCC. Furthermore, TGF-α might play a role in morphogenesis and regeneration of intrahepatic bile ducts.     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

AIM To study the phase cancer tissue intercellular adhesion molecule-1 (ICAM-1) expression of human cancer metastasis model in nude mice, and to analyze the relationship between ICAM-1 expression and the metastasis and recurrence of hepatocellular cancinoma (HCC).METHODS HCC tissues from liver cancer metastasis model in nude mice (LCI-D20) was orthotopically implanted, and ICAM-1 expression in HCC tissues at different growing time were detected by immunodot blot. Tumor size, intrahepatic and extrahepatic metastasis foci were observed by naked eyes and under light microscope.RESULTS ICAM-1 was positively correlated to the tumor growing time (r=0.88, P＜0.01) and tumor size r=0.5, P＜0.05). It was higher in metastatic HCC than in nonmetastatic HCC (8.24±0.95 vs 3.03±0.51, P＜0.01). ICAM-1 content in cancer tissues increased suddenly after metastasis occurred and then maintained in a high level. ICAM-1 was also higher in multimetastasis group than in monometastasis group (10.05±1.17 vs 5.48±0.49, P＜0.05).CONCLUSION Tissue ICAM-1 could predict not only the metastasis of human liver cancer metastasis model in nude mice early and sensitively, but also the metastasis degree. So tissue ICAM-1 may be a potential index indicating the status of metastasis of HCC patients.     

STAT5和WWOX在非小细胞肺癌中的表达及相关性研究

目的 探讨信号转导和转录激活因子5(STAT5)和WW结构域氧化还原酶(WWOX)在非小细胞肺癌(NSCLC)中的表达及相关性研究.方法 用免疫组化SP法检测40例手术切除的NSCLC组织和20例正常肺组织中STAT5和WWOX的蛋白表达.结果 STAT5蛋白在NSCLC中的表达明显高于正常肺组织,而WWOX在NSCLC中的表达明显低于正常肺组织(P<0.01);STAT5表达水平与NSCLC组织学类型有关,在腺癌组织中的表达明显高于鳞癌(P<0.01),WWOX的表达与淋巴结转移相关,有淋巴结转移的表达低于无淋巴结结转移(P<0.01);STAT5蛋白和WWOX蛋白在NSCLC组织中的表达呈负相关(P<0.05).结论 在NSCLC中存在STAT5的过度表达以及WWOX的失表达,STAT5表达水平与NSCLC组织学类型有关,而WWOX的表达与淋巴结转移相关.提示在NSCLC的发生机制中,WWOX可能通过抑制STAT5系统,促进细胞凋亡,起到抑癌作用.     

抑癌基因WWOX在哈萨克族食管鳞癌中表达的研究

目的探讨哈萨克族食管鳞癌中抑癌基因WWOX表达及意义,为哈萨克族的食管癌的早期诊断提供依据。方法收集新疆哈萨克族食管鳞癌患者癌组织、癌旁组织和正常食管组织标本各20例,HE染色观察癌组织的细胞学分型;免疫组化检测各组标本中WWOX的表达;RT-PCR检测各组标本中WWOX mRNA的表达。结果 WWOX蛋白在哈萨克族食管正常组织(65%)、癌旁组织(45%)及食管癌组织中(20%)的表达依次降低,各组间比较差异有统计学意义(P<0.05);WWOX mRNA的表达量在食管正常组织、食管癌旁组织及食管癌组织中的表达也依次降低,组间比较差异有统计学意义(P<0.05)。结论抑癌基因WWOX的低表达可能与哈萨克族食管癌的发生有关,对其表达的检测可能会成为哈萨克族食管癌早期诊断手段之一。