大肠癌组织中STAT3的表达及其对肿瘤血管生成的影响

目的:探讨大肠癌组织中信号转导子与转录活化子3(STAT3)的表达,并研究STAT3的表达对肿瘤血管生成的影响.方法:采用免疫组化方法检测大肠癌中STAT3、CD34的表达情况.结果:大肠癌中STAT3蛋白表达阳性率为63.6%(21/33).显著高于正常大肠组织的阳性率(P＜0.01);大肠癌组织中MVD为47.55±12.15,而正常大肠组织中MVD为11.67±1.08,两者相比具有显著差异(P＜0.01);大肠癌组织中STAT3的表达和MVD与肿瘤的恶性程度、Doke's分期有关及有无淋巴结转移有关(P＜0.05).相关分析表明STAT3表达和MVD呈显著正相关(r=0.788).结论:大肠癌组织中存在STAT3的高表达,STAT3的表达在大肠癌的病程发展及转移过程中发挥重要的作用.大肠癌的发生过程中STAT3可能调控肿瘤血管的生成,STAT3可能会成为大肠癌的抗血管生成新的治疗靶点.     

STAT3、 Bcl-xL、 Bax和CyclinD1在非小细胞肺癌中的表达

目的：分析STAT3、 Bcl-xL、 Bax和CyclinD1在非小细胞肺癌和正常肺组织中的表达及关系, 以进一步探讨其与非小细胞肺癌发生发展的关系.方法：利用SABC免疫组织化学技术检测84例非小细胞肺癌组织及30例正常肺组织中STAT3、 Bcl-xL、 Bax和CyclinD1的表达.结果：（1）STAT3、 Bcl-xL和CyclinD1在非小细胞肺癌组织中的表达水平明显高于正常肺组织（P＜0.05）, Bax在非小细胞肺癌组织有一定表达, 但与其在正常肺组织的表达比较无统计学意义（P＞0.05）;（2）STAT3、 Bcl-xL表达水平与非小细胞肺癌组织学类型有关, 在腺癌组织中的表达明显高于鳞癌, 与肿瘤大小、组织分化程度、 TNM分期及淋巴结转移无关;（3）Bax、 CyclinD1的表达水平与与组织学类型、肿瘤大小、组织分化程度、 TNM分期及淋巴结转移无关（P＞0.05）.结论：STAT3、 Bcl-xL和CyclinD1可能在肺癌的发生发展中发挥重要作用, 由此可望寻找到新的非小细胞肺癌的诊断方法和治疗靶点.     

紫外线光疗抑制早期蕈样肉芽肿皮损组织中BCL-2、STAT3、CCL17和CCL27的表达

<正>BCL-2是研究最早的与细胞凋亡相关的一类原癌基因。目前有关治疗前后BCL-2蛋白表达变化的研究仍较少,探讨治疗前后BCL-2蛋白表达的变化是目前需要进一步研究的问题。STAT3是信号传导和转录活化因子家族中与肿瘤关系最密切的基因之一,STAT3持续活化与肿瘤的发生发展和预后相关。CCL17和CCL27在淋巴细胞归巢机制中起重要作用,与受体结     

STAT3、WWOX与c-myc在非小细胞肺癌组织中的表达及相关性分析

目的:研究信号转导与转录激活因子3(STAT3)、包含氧化还原酶的WW结构域(WWOX)及原癌基因c-myc在非小细胞肺癌(NSCLC)及肺正常组织中的表达以及三者之间的关系。方法:应用免疫组化染色S-P法,检测STAT3、WWOX及c-myc在40例NSCLC组织和20例正常肺组织中的表达情况,并分析其与各个临床病理指标之间的关系。结果:(1)STAT3和c-myc在NSCLC组织中的阳性表达率分别为92.5%和90%,均明显高于肺正常组织(20%和15%,P0.01);WWOX在NSCLC中的阳性表达率为30%,明显低于肺正常组织(75%,P0.01)。(2)STAT3、c-myc的表达水平与NSCLC的组织学类型有关,在腺癌组织中的表达明显高于鳞癌组织(P0.01);与年龄、性别、肿瘤组织的分化程度、肿瘤大小、TNM分期及淋巴结转移无关;WWOX基因的表达与是否有淋巴结转移相关(P0.01),在有淋巴结转移的肺癌组织中其表达更低或缺失。(3)STAT3与WWOX在NSCLC组织中的表达呈显著负相关(r=-0.443,P0.01);STAT3与c-myc蛋白,WWOX与c-myc在NSCLC组织中的表达均不相关(分别为r=-0.084,r=0.115)。结论:在NSCLC组织中存在STAT3和c-myc的过度表达,WWOX在NSCLC组织中呈低表达或表达缺失,提示三者可能参与了NSCLC的发生与发展;在NSCLC的发生过程中,STAT3蛋白与WWOX在NSCLC中的表达呈负相关;而STAT3与c-myc、WWOX与c-myc的表达均无相关性,它们二者之间可能是通过两条不同的途径影响肺癌的发生与发展。     

IL-6和AG490对Burkitt淋巴瘤细胞生长的影响

 目的: 观察IL-6和AG490对Raji细胞生长的影响,探讨信号转导及转录激活因子3(STAT3)及survivin在Burkitt淋巴瘤发生发展中的作用,为寻找淋巴瘤生物治疗的新靶标提供实验依据。方法: 培养Raji细胞,分别加入STAT3的激动剂IL-6和抑制剂AG490,用real-time PCR和Western blot检测STAT3、survivin的表达情况及STAT3的磷酸化,MTT法检查细胞活力,流式细胞术检测细胞凋亡和细胞周期变化。结果: 培养细胞中加入IL-6或AG490后,细胞生长受明显影响并呈现药物浓度依赖关系(P<0.05);与相应的对照组比较,IL-6组Raji细胞中STAT3、survivin mRNA的表达明显升高,AG490组Raij细胞中STAT3、survivin的mRNA表达明显降低。不同浓度的IL-6组之间、不同浓度的AG490组之间,STAT3和survivin mRNA的表达亦有显著差异(P<0.05),且2种基因mRNA表达都呈现出药物浓度依赖关系。p-STAT3、STAT3和survivin的蛋白水平在IL-6作用下表达增高,AG490作用下表达降低;细胞凋亡率在IL-6作用下逐渐降低,在AG490作用下逐渐升高,且都呈现出药物浓度依赖关系;经AG490处理后,G₁期Raji细胞明显增加,S期细胞无明显改变,G₁/S比值增加,而在IL-6组中,S期细胞明显降低。结论: IL-6和AG490对Raji细胞生长有明显影响,STAT3及其下游靶基因survivin的表达改变可能是IL-6及AG490影响Raji细胞生长的重要分子机制。     

EB病毒与乳腺癌相关性的研究进展

肿瘤病因学纷繁复杂,人们试图从病毒方面来阐明肿瘤的发生机制,包括探索EB病毒(EBV)与各种肿瘤的关系.目前认为EBV与多种淋巴瘤(例如Burkitt淋巴瘤、Hodgkin淋巴瘤和移植后淋巴组织增生性疾病等)以及一些上皮源性恶性肿瘤(例如鼻咽癌、胃腺癌等)的发生相关.     

Diffuse Large B Cell Lymphoma in Hyper-IgE Syndrome Due To <Emphasis Type="Italic">STAT3</Emphasis> Mutation

The Job or hyper-immunoglobulinemia E syndrome is a primary immunodeficiency that is usually inherited in an autosomal dominant fashion. With the discovery of mutations in the STAT3 gene in the majority of autosomal dominant cases, it is now possible to make a molecular diagnosis of hyper-IgE syndrome. Both primary and secondary immunodeficiencies, including hyper-IgE syndrome, may predispose for malignancies, especially lymphomas, mainly mature B cell lymphomas, and classical Hodgkin lymphoma. Here, we report of a 48-year-old male with hyper-IgE syndrome who developed a primary parotid gland diffuse large B cell lymphoma. Analysis for STAT3 mutations demonstrated that the causal mutation of hyper-IgE syndrome, R382Q, arose de novo in the patient and it was transmitted to three of his five children, all three of whom are clinically affected. We review the literature regarding lymphoma in hyper-IgE syndrome and the possible etiologic relationship with STAT3 mutations.     

Pax5 expression in non-Hodgkin's lymphomas and acute leukemias

The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffin embedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.     

Cyclin D3 expression in normal,reactive and neoplastic tissues

Cyclin D3 immunohistochemical expression was investigated in normal, reactive, and neoplastic human embryonal and adult tissues. In the fetus, cyclin D3 was expressed in selected developmental phases of a limited number of cell systems. In normal adult tissues, cyclin D3 showed two patterns of distribution: in lymphoid tissues it was expressed in proliferative compartments, while in most other tissues it was expressed by terminally differentiated/quiescent cells. This dual role in proliferation and differentiation was partially conserved in neoplasms. In non-Hodgkin lymphomas, cyclin D3 immunolabelling was correlated with proliferative activity and progression; a significant exception was seen in cyclin D1-positive mantle cell lymphomas, which were cyclin D3-negative. Benign endocrine tumours were frequently strongly cyclin D3-positive, while high-grade (small cell) neuroendocrine carcinomas were always negative. In most other epithelial neoplasms, cyclin D3 immunostaining was heterogeneous. In breast carcinomas, no relationship was seen between ER status and MIB1 labelling; cyclins D3 and D1 were frequently expressed in the same tumour, while occasional tumours showed an inverse quantitative relationship between cyclins D1 and D3, and rare tumours were negative for both. In soft tissue neoplasms, cyclin D3 was consistently expressed in some tumours, such as stromal tumours of the gastrointestinal tract and embryonal rhabdomyosarcomas. Our data suggest that cyclin D3 has a dual role in proliferation and differentiation in normal tissues and in some neoplastic conditions; that the cyclin D3 expression pattern is different from cyclin D1, suggesting non-redundant functions; that cyclin D3 expression is strong in endocrine cells secreting steroid hormones, and in their neoplastic counterparts; and that cyclin D3 deregulation may be of pathogenetic relevance in lymphomagenesis and could be diagnostically useful. © 1998 John Wiley & Sons, Ltd.