CC10 在非小细胞肺癌中的表达及其与癌细胞凋亡的关系

目的：研究CC10蛋白在非小细胞肺癌（NSCLC）中的表达，并观察其与癌细胞凋亡的关系。方法：采用免疫组化技术检测CC10蛋白在43例NSCLC及20例癌旁正常肺组织石蜡标本中的表达，并借助HPIAS-1000图像系统对结果进行分析。应用TUNEL技术检测43例NSCLC中癌细胞的凋亡情况。结果：CC10蛋白在NSCLC中的表达率为46．5％（20／43），明显低于癌旁正常肺组织的85．0％（P〈0．01）；CC10蛋白在肺癌中的表达水平与分化程度、TNM分期及淋巴结转移有关，但与性别、年龄、肿瘤大小、肿瘤组织学分型无关（P〉0．05）；CC10蛋白阳性的肺癌组织细胞凋亡指数（AI）为（5．585±1．7822）％，CC10蛋白阴性的肺癌组织为（2．856±1．3990）％，差异有显著性，癌细胞AI与NSCLC中CC10蛋白的表达有显著相关性（rs=-0．0211，P〈0．05）。结论：CC10蛋白的表达下调可能在NSCLC的发生发展中起重要作用，NSCLC细胞的凋亡与CC10蛋白的表达下调密切相关     

乙酰肝素酶mRNA在非小细胞肺癌中的表达及意义

目的 探讨乙酰肝素酶(HPA)mRNA在非小细胞肺癌(NSCLC)组织中的表达及其与NSCLC临床病理特征的关系.方法 采用SYBR GreenⅠ实时荧光定量逆转录聚合酶链反应(real-time RT-PCR)方法检测HPA mRNA在48例NSCLC癌组织、10例癌旁正常肺组织以及10例肺良性疾病肺组织中的表达水平.结果 HPA mRNA在NSCLC组织平均表达水平(8.244±5.314)明显高于癌旁(1.043±0.478)及良性疾病肺组织(1.025±0.465)(P<0.01);在NSCLC组织中HPA的高表达与肿瘤病理类型(P<0.05)、淋巴结转移(P<0.05)和临床分期(P<0.01)有关,而与患者的年龄、性别、吸烟情况以及分化程度无关.结论 HPA在人肺癌组织中的表达量较正常肺组织明显上调并与非小细胞肺癌的侵袭、浸润以及转移有关.     

RhoE、p53和caspase-3在非小细胞肺癌中的表达及其临床意义

目的 探讨RhoE、p53和caspase-3蛋白在非小细胞肺癌(NSCLC)组织中的表达与不同临床病理特征的关系及三者在肺癌发生过程中可能存在的相关性.方法 采用SP法检测60例NSCLC组织和23例正常肺组织中RhoE、p53和caspase-3蛋白的表达情况.结果 非小细胞肺癌组织中RhoE、p53和caspase-3蛋白阳性表达率分别为8.33%、86.67%、68.33%.RhoE在NSCLC中的表达与TNM分期(P<0.01)和淋巴结转移有关(P<0.05).RhoE与p53和caspase-3蛋白的表达呈负相关(P<0.01,P<0.05).结论 RhoE在癌组织中表达下调,说明RhoE在肺癌的发生、发展中发挥重要作用;RhoE蛋白表达与肺癌的TNM分期密切相关,有可能作为判断病情和评价预后的新指标;RhoE与p53、caspase-3的表达均呈负相关,有望为肺癌基因治疗提供新的靶点.     

Skp2蛋白在非小细胞肺癌中的表达与预后

目的:研究Skp2蛋白在非小细胞肺癌中的表达及其指标的关系,以探讨其在预后中的意义。方法:纳入武汉大学人民医院1995-01/2001-1242例非小细胞肺癌(NSCLC)组织,10例肺良性病变及8例癌旁不典型增生石蜡组织切片。采用免疫组化技术检测Skp2蛋白在42例NSCLC、10例肺良性病变、8例癌旁不典型增生组织中的表达,并借助HPIAS-1000图像分析系统对结果进行分析。结果:肺癌组织中Skp2蛋白的阳性率为(24.83±13.64)%,明显高于肺良性病变组织(3.07±1.32)%(P<0.01),也高于癌旁不典型增生组织(13.89±3.95)%(P<0.01)。Skp2蛋白表达水平与分化程度、TNM分期及淋巴结转移有密切关系,但与年龄、性别、肿瘤组织学分型无明显关系。结论:Skp2蛋白的过量表达在NSCLC的发生发展中起重要作用,Skp2蛋白可能为肺癌的一个独立预后因子,与肺癌患者的生活质量可能有一定的关系。     

非小细胞肺癌中DLEC1的表达缺失与临床病理因素的相关研究

目的:探讨DLEC1蛋白在非小细胞肺癌(NSCLC)中的表达及其临床意义.方法:应用免疫组织化学Elivision法检测83例NSCLC及83例相应癌旁组织中DLEC1的表达,分析在不同临床病理指标下DLEC1蛋白的表达情况.结果:NSCLC组织中DLEC1蛋白的失表达率为74.70%(62/83),显著高于癌旁组织中的失表达率32.53%(27/83)(P<0.05).DLEC1的表达与NSCLC组织学类型、淋巴结转移及TNM临床分期密切相关(P<0.05),但与患者的年龄、性别、肿块大小、分化程度无关(P>0.05).结论:DLEC1在非小细胞肺癌中失表达,可能对NSCLC的发生发展起着一定的作用.     

凋亡抑制蛋白Livin在非小细胞肺癌中的表达及临床意义

目的:研究凋亡抑制蛋白Livin两种异构体Livinα、Livinβ在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与NSCLC生物学特点的相关性。方法:采用逆转录聚合酶链反应法检测48例NSCLC组织、29例癌旁组织和13例良性病变肺组织中LivinmRNA,并用组织芯片免疫组织化学SP法检测Livin蛋白的表达水平,结合临床病理资料进行分析。结果:Livinα和Livinβ在NSCLC组织中多同时表达,LivinmRNA和Livin蛋白的表达水平基本一致。Livin在NSCLC组织、癌旁组织和良性病变肺组织中的表达阳性率分别为66.7%、6.9%和0(P<0.05)。在淋巴结转移组,其表达阳性率为76.5%,高于无转移组的42.9%(P<0.05),而与NSCLC的病理类型、分化水平和临床分期无明显相关性(P>0.05)。结论:Livin在NSCLC组织中特异性地高表达,可能成为NSCLC诊断上新的标记物和治疗上新的靶点。     

非小细胞肺癌p53凋亡刺激蛋白家族表达临床研究

目的:探讨非小细胞肺癌p53凋亡刺激蛋白家族(apoptosis-stimulating protein of p53,ASPP)1,ASPP2mRNA表达与P53蛋白表达状态的关系及ASPP1,ASPP2 mRNA的表达与非小细胞肺癌发生的相关性.方法:应用实时荧光定量RT-PCR方法检测37例非小细胞肺癌患者癌组织、癌旁组织、正常肺组织ASPP1,ASPP2 mRNA表达,免疫组织化学法检测肺癌组织P53蛋白表达状态.结果:肺癌组织、癌旁组织、正常肺组织中ASPP1、ASPP2 mRNA表达均逐渐升高,肺癌组织ASPP1,ASPP2 mRNA表达低于癌旁组织和正常肺组织(P<0.05),癌旁组织和正常肺组织ASPP1、ASPP2 mRNA表达差异无统计学意义(P>0.05).肺癌组织中ASPP1,ASPP2 mRNA表达在P53阴性组中明显低于P53阳性组(P<0.05).结论:肺癌组织ASPP1、ASPP2 mRNA表达降低与非小细胞肺癌的发生密切相关,ASPP mRNA的表达可在基因水平检测肿瘤的发生.     

肝细胞核因子3β在人类肺癌组织中的表达及意义

目的 探讨肝细胞核因子3β蛋白(HNF-3β)在非小细胞肺癌(NSCLC)组织和癌旁正常肺组 织中的表达情况,探讨其临床意义.方法 分别采用免疫组化法和RT-PCR 方法检测50 例NSCLC 组织及癌 旁正常肺组织中HNF-3β蛋白和mRNA 的表达.结果 HNF-3β蛋白在NSCLC 和正常癌旁组织中的半定量 评分分别为0.42 ±0.13,2.28 ±0.28,差异有统计学意义(P <0.05).HNF-3βmRNA 在NSCLC 和正常癌旁 组织中的半定量评分分别为1.32 ±0.23,3.68 ±0.32,差异有统计学意义(P <0.05).结论 初步认定HNF- 3β对人类非小细胞肺癌的形成起抑制作用.     

应用组织芯片技术检测非小细胞肺癌中骨桥蛋白和基质金属蛋白酶-9的表达及其临床意义

目的:探讨人非小细胞肺癌(NSCLC)组织中骨桥蛋白(OPN)和基质金属蛋白酶-9(MMP-9)蛋白的表达及临床意义。方法:利用组织芯片技术结合免疫组化法检测48例NSCLC组织、19例癌旁组织及13例良性病变组织中OPN和MMP-9蛋白的表达。结果:OPN和MMP-9的阳性表达率在癌组织中分别是75.0%、70.8%;在癌旁组织中分别是13.8%、17.2%;在良性病变组织分别是23.1%、30.8%。NSCLC组织中OPN和MMP-9蛋白表达均显著高于癌旁组织及良性病变组织,差异具有统计学意义(P<0.05)。此外,OPN和MMP-9表达率与患者组织学类型、TNM分期及淋巴结转移有密切关系(P<0.05)。OPN与MMP-9蛋白表达存在正相关(r=0.58,P<0.05)。结论:OPN和MMP-9的表达与NSCLC的发生、发展有关,联合检测有助于判断NSCLC患者的预后。     

组织因子途径抑制物-2在非小细胞肺癌中的表达及其与细胞凋亡的关系

目的:探讨非小细胞肺癌中组织因子途径抑制物-2(TFPI-2)的表达及其与细胞凋亡的关系.评价其与肺癌恶性程度的关系.方法:收集非小细胞肺癌石蜡标本、临床资料和临床分期.采用免疫组化法检测TFPI-2蛋白在60例非小细胞肺癌和15例正常肺组织中的表达水平.并应用末端脱氧核苷酸转移酶介导的标记染色法(TUNEL法)检测细胞凋亡,计算凋亡指数(AI).结果:TFPI-2在非小细胞肺癌中的表达指数为60.0%,低于正常肺组织的89.5%.Ⅰ、Ⅱ期及无转移的非小细胞肺癌组织中TFPI.2表达指数(70.9%)及 AI值[(9.58±4.52)%]均高于Ⅲ、Ⅳ期[48.3%、(6.36±1.98)%]及有转移的非小细胞肺癌组织[57.1%、(6.10±2.68)%],差异有统计学意义(P<0.05).结论:TFPI-2在正常肺组织中的表达水平明显高于非小细胞肺癌组织,TFPI-2可能在诱导非小细胞凋亡中起到重要作用.     

Small cell lung cancer

Lung cancer is the most common cause of cancer death in the United States, with approximately 135,000 men and women dying each year. While much has been learned about the etiologic risk factors, less progress has been made in therapy. Five-year survival rates remain at less than 10%. However, there has been some progress in the therapy of one histological subtype of lung cancer, small cell lung cancer. Totaling around 20% of lung cancer cases, small cell lung cancer is distinct from the other histologic subtypes in its biologic behavior and responsiveness to therapy. In the 1960s, the median survival for patients with small cell lung cancer was approximately 3 months. With combination chemotherapy and radiotherapy median survivals now range from 1 to 2 years, and there is evidence for a curative potential since approximately 10% of patients who initially present with limited disease survive greater than 2 years. The unique clinical aspects of this histological subtype potentially relate to its underlying cell of origin. This behavior is reflected in the numerous paraneoplastic syndromes that frequently accompany small cell lung cancer. Its propensity for early dissemination have made staging the extent of disease an important part of the clinical evaluation. Since small cell lung cancer is sensitive to both chemotherapy and radiation therapy, there have been multiple clinical trials evaluating drug/radiotherapy combinations. This article will briefly describe the unique aspects of small cell lung cancer as opposed to other histological subtypes of lung cancer and give an overview of the current clinical approach and treatment of this disease.     

Non-small cell lung cancer

Lung cancer stands as the most important malignant neoplasm in the United States because of its high prevalence, increasing incidence, high rate of mortality, and great potential for prevention through the control of cigarette smoking. The World Health Organization (WHO) classification of lung cancer identifies four major types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and small cell carcinoma. These tumors are commonly divided into two groups based on differences in their biology and treatment: small cell (SCLC) and non-small cell carcinomas (NSCLC). This review analyzes NSCLC with a strong emphasis on the practical aspects of treatment. We give recommendations about smoking cessation and early diagnosis through screening of high-risk individuals. We review contemporary diagnostic and staging techniques in the context of the new international TNM system of staging. Subsequent discussions of treatment are based on this new staging system. We stress the pivotal role of surgery for the management of local disease, and in addition present the potential contributions of newer radiation therapy techniques. We examine chemotherapy in detail, including a review of the comparative activity of the available cytotoxic agents against NSCLC, the relative contribution of combination chemotherapy, and the role of surgical adjuvant treatment with either chemotherapy or immunotherapy. We advise that patients with NSCLC be treated under the aegis of modern clinical trials of new therapy whenever possible. When this is not possible, we recommend an individualized approach based on such factors as the patient's age, general state of health, cardiopulmonary status, psychosocial status, and personal system of values.     

Small cell lung cancer

Small cell lung cancer accounts for approximately 15% of bronchogenic carcinomas. It is the cancer most commonly associated with various paraneoplastic syndromes, including the syndrome of inappropriate antidiuretic hormone secretion, paraneoplastic cerebellar degeneration, and Lambert-Eaton myasthenic syndrome. Because of the high propensity of small cell lung cancer to metastasize early, surgery has a limited role as primary therapy. Although the disease is highly sensitive to chemotherapy and radiation, cure is difficult to achieve. The combination of platinum and etoposide is the accepted standard chemotherapeutic regimen. It is also the accepted standard therapy in combination with thoracic radiotherapy (TRT) for limited-stage disease. Adding TRT increases absolute survival by approximately 5% over chemotherapy alone. Thoracic radiotherapy administered concurrently with chemotherapy is more efficacious than sequential therapy. Furthermore, the survival benefit is greater if TRT is given early rather than late in the course of chemotherapy. Regardless of disease stage, no relevant survival benefit results from increased chemotherapy dose intensity or dose density, altered mode of administration (eg, alternating or sequential administration) of various chemotherapeutic agents, or maintenance chemotherapy. Prophylactic cranial radiation prevents central nervous system recurrence and can improve survival. In Japan and some other Asian countries, the combination of irinotecan and cisplatin is the standard chemotherapeutic regimen. Clinical trials using thalidomide, gefitinib, imatinib, temsirolimus, and farnesyltransferase inhibitors have not shown clinical benefit. Other novel agents such as bevacizumab have shown promising early results and are being evaluated in larger trials.     

肿瘤坏死因子凋亡诱导配体蛋白对前列腺癌及膀胱癌细胞抑制作用的研究

目的研究重组并纯化的肿瘤坏死因子凋亡诱导配体蛋白(TRAIL)对前列腺癌(PC-3)及膀胱癌细胞(5637)的抑制作用。方法 PC-3和5637细胞分为对照组(仅加培养液)和实验组(加入40 ng/ml的TRAIL蛋白处理),细胞培养12 h后加入TRAIL蛋白,24 h后应用PCR、Western blot技术检测细胞内抗凋亡蛋白Bcl-2及凋亡信号通路中Caspase-3和Caspase-8基因和蛋白的表达。结果应用SPSS统计分析软件,组间比较采用t检验,结果显示:PC3和5637细胞在TRAIL蛋白作用24 h后Bcl-2基因和蛋白表达水平均降低,而Caspase-8、Caspase-3基因和蛋白表达则增加。与对照组相比,其差异具显著性意义。结论 TRAIL蛋白通过下调抗凋亡基因Bcl-2的表达,增强Caspase-8、Caspase-3的表达从而诱导两种肿瘤细胞的凋亡达到抑癌效应。     

Treatment of small cell lung cancer

The prognosis for patients with small cell lung cancer has improved over the past ten years from a median survival of 2.5 months to 8 to 10 months for patients with extensive metastatic disease and 12 to 16 months for patients with limited disease. This progress has been primarily through advances in chemotherapy. A small percentage of patients are having prolonged disease-free survival. Methods of staging are reviewed. The best current chemotherapeutic programs are discussed, as well as the present role of radiation therapy in the management of small cell lung cancer.