Livin、Survivin蛋白在非小细胞肺癌中的表达及意义

目的研究Livin、Survivin蛋白在非小细胞肺癌(NSCLC)中的表达及意义。方法采用免疫组化SP法检测45例NSCLC病人的癌和癌旁组织标本中Livin及Survivin的表达,分析其与临床参数的关系以及二者表达的相关性,并通过随访研究其与NSCLC患者5年生存率的关系。结果 Livin和Survivin在NSCLC癌组织中的阳性表达率均显著高于癌旁组织(P0.05),在NSCLC癌组织中的表达与患者性别、年龄、是否吸烟、癌组织类型、肿瘤的大小、分化程度和TNM分期均无关(P0.05),而与是否有淋巴结转移有关(P0.05);Livin和Survivin的表达无相关性;Livin和Survivin表达阳性者5年生存率均明显低于表达阴性者(P0.05)。结论 Livin和Survivin蛋白与NSCLC发生、发展、转移及预后有关,对NSCLC临床诊断和预后判断具有一定的指导意义。     

Survivin和Livin蛋白在非小细胞肺癌中的表达及临床意义

目的 研究Survivin和Livin蛋白在非小细胞肺癌(NSCLC)组织中的表达及其临床意义,并分析两者的相关性.方法 用免疫组织化学SP法检测50例NSCLC组织、21例癌旁正常肺组织中Survivin和Livin蛋白的表达水平,并分析其与临床病理特征的关系.结果 Survivin蛋白在NSCLC中的阳性表达率显著高于癌旁正常肺组织(P＜0.05),Livin蛋白在NSCLC中的阳性表达率显著高于癌旁正常肺组织(P＜0.05).Survivin蛋白表达的阳性率与分化程度相关(P＜0.05),Livin蛋白表达的阳性率与淋巴结转移相关(P＜0.05).Survivin和Livin蛋白表达无相关性.结论 Survivin、Livin在NSCLC的发生、发展过程中起着重要的作用,联合检测可为NSCLC的的早期诊断、进一步治疗提供必要的理论依据.     

非小细胞肺癌中TFPI-2与Survivin表达关系的研究

目的 探讨非小细胞肺癌中组织因子途径抑制物-2(TFPI-2)的表达与Survivin的关系,从而评价其在肺癌细胞凋亡中的作用.方法 采用免疫组化法检测TFPI-2、Survivin蛋白在75例非小细胞肺癌和20例正常肺组织中的表达水平.结果 TFPI-2在非小细胞肺癌中的表达指数为55％,低于正常的肺组织85％.Survivin在非小细胞肺癌中的阳性表达水平为71％,在正常肺组织中大表达水平为5％.TFPI-2和Survivin在非小细胞肺癌中的阳性表达水平呈现负相关(r=9.62,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,其可能通过调控Survivin蛋白的表达来抑制肿瘤细胞的浸润转移.     

凋亡相关基因Survivin在非小细胞肺癌中的表达及意义

目的研究Survivin在非小细胞肺癌(NSCLC)中的表达及临床生物学意义。方法采用免疫组化S-P法检测Survivin在NSCLC及癌旁正常肺组织中的表达情况。采用TUNEL法检测凋亡细胞,计算凋亡指数(AI)。结果 60例NSCLC组织中Survivin的阳性表达率为46.7%,20例正常肺组织的阳性表达率为10.0%,差异有统计学意义(P<0.01)。Survivin的阳性表达与有无淋巴结转移、肿瘤的分化程度及TNM分期有关(P<0.05),与NSCLC患者的年龄、性别、肿瘤直径、病理分型、是否吸烟及有无胸膜转移无关(P>0.05)。结论 Survivin基因的异常表达可能在NSCLC的发生、发展中起到一定作用。检测Survivin可能有助于临床TNM分期和有无淋巴结转移的判断。     

P63蛋白在非小细胞肺癌中表达研究

目的研究宣威与非宣威地区非小细胞肺癌P63蛋白的表达,探讨其与生物学行为的关系。方法免疫组织化学法。结果 P63在肺鳞癌组织中高表达;非小细胞肺癌中,P63的表达与患者的TNM分期、组织分化程度及淋巴结转移情况有关,与患者性别无关;P63在非小细胞肺癌中在相同病理类型、分期、组织分化、淋巴结转移情况及相同性别的阳性表达率,宣威组与非宣威组比较,差异无统计学意义。结论P63的表达在宣威并无地区特异性,并不是宣威肺癌高发的原因。     

Survivin的表达与非小细胞肺癌生物学特征及预后的关系

目的探讨凋亡抑制基因Survivin的表达与非小细胞肺癌(NSCLC)生物学特征及临床预后的关系。方法应用免疫组化检测了70例NSCLC中Survivin的表达,并选取30例癌旁组织作为对照,比较Survivin的表达与NSCLC患者生物学特征及预后的关系。结果Survivin在NSCLC中的阳性表达率为74.3%,而癌旁组织无1例表达,Survivin的表达与肺癌患者年龄、性别、病理类型、分化程度无关(P0.05),与临床分期有关(P=0.008);Survivin表达阳性者生存时间明显低于阴性表达者(P=0.000),COX回归显示Survivin与NSCLC患者预后有关(P=0.001)。结论Survivin与NSCLC的发生发展有关,过度表达提示预后不良,Survivin有望成为肺癌诊断和基因治疗的新靶点。     

WDHD1蛋白在非小细胞肺癌中的表达及临床意义

目的探讨WDHD1蛋白在非小细胞肺癌发生,发展,浸润和转移中的作用。方法用免疫组化MaxVision法检测WDHD1蛋白在肺鳞癌,腺癌和正常肺组织中的表达。结果 WDHD1蛋白在非小细胞肺癌组织中的表达明显高于周围正常肺组织(P0.05),其表达与非小细胞肺癌临床分期(P0.05)、浸润范围(P0.05)、淋巴结转移(P0.05)和组织分化程度(P0.05)有关。结论 WDHD1蛋白在非小细胞肺癌中高表达,与非小细胞肺癌分化差、恶性程度、临床分期、淋巴结转移密切相关,在非小细胞肺癌的发生发展过程中可能起重要作用.     

肺癌耐药蛋白在非小细胞肺癌中的表达与临床相关性研究

目的：探讨肺癌耐药蛋白（LRP）在非小细胞肺癌（NSCLC）中的表达与临床相关性。方法：通过纤维支气管镜活检、经皮肺穿刺活检或手术切除而药取肺癌组织标本69例,其中男52例,女17例。I、Ⅱ期28例,Ⅲ、Ⅳ期41例。采用免疫组织化学法进行检测,胞浆呈棕黄色着染为LRP阳性。结果：LRP主要表达于胞浆,69例肺癌组织中,LRP表达阳性39例,男性56％（29／52）,女性59％（10／17）,总检出率57％（39／69）,各年龄段间差异无显著性。肺腺癌中检出率67％（18／27）,肺鳞癌中检出率55％（17／31）;T1－2中检出率52％（23／44）,T3－4中检出率64％（16／25）;N3中检出率83％（5／6）;在M0中检出率57％（36／63）,M1中检出率50%(3/6)。LRP表达与NSCLC中组织类型无相关性（P＞0．05）,与原发灶的侵犯范围（T）及转移情况（N、M）无关。LRP阳性组化疗有效率低于LRP阴性组（P＜0．05）。随访中LRP阳性组死亡7例,LRP阴性组死亡3例。结论：在肺腺癌与鳞癌中由LRP引起的耐药发生机率相等;TNM指标只代表肿瘤进展而不代表耐药性差异;LRP在NSCLC中的表达与化疗的有效率及预后有一定的相关性,LRP表达阳性者预后差。有研究报道LRP的表达与多药耐药有关,LRP的检测能指导化疗方案的选择,提高化疗疗效,因此,值得进一步深入研究。     

P27蛋白在非小细胞肺癌中表达的预后意义

Ｐ2 7蛋白具有限制性调节细胞周期进程的作用 ,这一作用主要通过抑制细胞周期蛋白依赖性激酶 (ＣＤＫＳ)复合物的功能来实现。Ｐ2 7蛋白表达与预后的关系在乳癌、淋巴瘤、前列腺癌以及消化道肿瘤已有报道[1] ,而在肺癌中的研究甚少。我们运用免疫组化法检测Ｐ2 7在非小细胞性肺癌组织中的表达水平 ,从而探讨其在非小细胞性肺癌中的意义。对象和方法　 1 对象 :5 6例非小细胞肺癌 (ＮＳＣＬＣ)病例均在本院接受治疗及随访。其中男 42例 ,女 14例 ,年龄39～ 77岁 ,平均 6 0岁。中位随访时间 2年 (1～ 5年 ) ,5 6例ＮＳＣＬＣ中 ,腺癌 36例 ,鳞…     

Survivin表达与非小细胞肺癌预后关系的Meta分析

目的探讨细胞凋亡抑制蛋白存活素(Survivin)的表达与非小细胞肺癌预后的关系。方法检索PubMed以及CNKI中文数据库中研究Survivin表达与非小细胞肺癌预后关系的文献,并根据纳入和排除标准进行筛选,收集纳入文献的生存率,应用RevMan5软件对文献进行Meta分析。结果共入选10篇文献,累计病例980例。对入选10篇文献进行一致性检验,P<0.01,适用随机效应模型,合并相对危险度(RR)为1.55,95%可信区间为1.21～1.97,P<0.001。结论 Survivin的阳性表达可能是非小细胞肺癌不良预后的一个标志。     

Survivin与肺癌关系的研究进展

survivin是凋亡抑制蛋白（inhibitor of apoptosis protein,IAP）家族中的新成员,具有抑制细胞凋亡和调节细胞分裂的双重功能。survivin基因广泛表达于胚胎发育组织,在成人终末分化组织低表达或不表达,而在绝大多数肿瘤组织中高表达。研究显示,survivin在肿瘤的发生发展中起重要作用,与肿瘤预后密切相关,有望成为一种新的肿瘤诊断标志物,并可能成为抗肿瘤治疗的理想标靶。本文就survivin在肺癌中研究进展综述如下。     

Role of vindesine in induction chemotherapy in locally-advanced non-small-cell lung cancer

Locally advanced non-small-cell lung cancer (NSCLC) in most cases is not curable at the present time. Owing to the local extent of the tumor, the rate of complete resections is low and, therefore, survival in these patients is poor. For this reason, induction chemotherapy is being investigated in patients expected to have a poor prognosis after standard surgery and radiotherapy. The rationale for induction chemotherapy is to increase the rate of complete resections and achieve early elimination of micrometastases. Clinical investigations have reported an improvement of survival in stage III NSCLC after induction chemotherapy by using different combinations of cytotoxic drugs. Vindesine ranks among the most active single agents in this disease and has been part of a number of combination regimens in induction chemotherapy. The combination of mitomycin, vindesine or vinblastine and cisplatin has produced encouraging results in several studies, indicating a possible improvement of survival in stage III NSCLC, although its superiority to other combinations yet has to be demonstrated. Received: 11 July 1997 / Accepted: 30 September 1997     

Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications

Purpose  The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors. Methods  This study accrued subjects suspected to have lung cancer who underwent diagnostic bronchoscopy. Bronchoscopically-biopsied specimens were subjected to routine pathologic examination, and immunohistochemical studies were then performed if lung cancer was diagnosed. Chromogranin-A, synaptophysin, neural cell adhesion molecule, and Leu7 were used to demonstrate NE differentiation. Results  A total of 280 subjects were accrued to this study over a period of 2 years. Among them, 149 subjects were assessable for this study, and 130 were diagnosed as having NSCLC tumors (55 adenocarcinomas, 50 squamous cell carcinomas, 24 NSCLCs not otherwise specified, and 1 typical carcinoid). Large cell NE carcinoma was not observed in this study. Immunohistochemically, NE differentiation was detected in 16% of NSCLC tumors excluding typical carcinoid. By status of NE differentiation of NSCLC tumors, progression-free survivals were similar in 73 patients undergoing non-surgical treatment (positive, n = 10; negative, n = 63) and 43 patients undergoing surgical resection (positive, n = 8; negative, n = 35), respectively. Overall survival of patients with NE-positive tumors appeared to be favorable both for those undergoing non-surgical treatment and those undergoing surgical resection, though the differences in survival were not significant (P = 0.11 and 0.35, respectively). Conclusions  NE differentiation was detected in 16% of NSCLC tumors in our study. However, the prognostic implications of the presence of this feature could not be clearly determined in this study.     

Correlation between survivin expression and prognosis in non-small cell lung cancer

AIMS AND BACKGROUND: Survivin is a recently identified protein as an inhibitor of apoptosis, which supresses programmed cell death and regulates cell division. In this study, we investigated the prognostic significance of both nuclear and cytoplasmic survivin expression in non-small cell lung cancer (NSCLC) and examined the association with clinicopathological parameters. METHODS: The study comprised 58 male patients diagnosed NSCLC with a mean age of 57.29+/-8.82 years; range 40-76 years. Patients underwent lobectomy (64%) or pneumonectomy (36%) with hilar and mediastinal lymph node sampling. Paraffin embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin. Clinicopathological data, stage and survival of patients were all determined. RESULTS: Cytoplasmic staining was found significantly increased in squamous cell carcinoma (P=0.003), whereas there was no association between nuclear staining and histopathological type (P=0.837). Also, both nuclear and cytoplasmic staining did not show any association with tumor stage (P>0.05). In univariate analysis there was significant correlation between nuclear survivin and short survival (P=0.0002). In multivariate survival analysis using Cox regression, only nuclear staining of survivin was determined as an independent prognostic factor (P=0.004). CONCLUSIONS: Localization of survivin expression might have an important regulatory mechanism in carcinogenesis and tumor progression. Nuclear survivin expression in tumor tissues might predict the prognosis in NSCLC, whereas cytoplasmic survivin has no prognostic significance.     

A practical prognostic index for inoperable non-small-cell lung cancer

Radical radiotherapy is widely used to treat inoperable non-small-cell lung cancer (NSCLC) although only a small number of patients benefit in the long run from this intensive treatment. There is a small proportion of long-term survivors who might derive advantage from even more aggressive radiotherapy combined with chemotherapy. In order to support optimal treatment selection we have carried out univariate and multivariate analyses of possible prognostic variables in the retrospective data of 502 NSCLC patients treated at one institute with external radiotherapy, both with curative and palliative intent. To obtain more accurate tools for a rational treatment decision, we identified, by using Cox's proportional-hazards model, the five most powerful determinants of overall survival and combined them to a prognostic index. On the basis of only the number of these risk factors (advanced stage, general or metastatic symptoms, poor performance status, anemia and tumor size of at least 7 cm), the patient falls into one of the six possible prognostic groups and these groups turned out to be identifiable as separate prognostic clusters. Thirty-one per cent of the patients have three or more risk factors and a median survival of 5–7 months compared with 18 months for patients without any non-favorable factor. Furthermore, the prognostic factors were so strong that multivariate analyses did not reveal the treatment selection to have any significant influence on survival. As each of the five variables have the advantage of being routinely available, our index is simple enough to be used in daily clinical practice. The clinical value of the prognostic index should be verified by using independent data.Abbreviation NSCLC non-small-cell lung cancer This study was supported financially by the Finnish Cancer Society and Medical Research Fund of Tampere University Hospital     

非小细胞肺癌的联合靶向治疗

虽然化疗对于晚期非小细胞肺癌患者的预后有一定疗效,但已进入一个平台期.特别对于化疗无效的患者,亟需新的、更有效的治疗方法.随着研究人员对肿瘤细胞生长、运动、转移以及肿瘤血管生成机制的深入了解,靶向治疗成为研究的热点.本文综述了现在主要使用的分子靶向药物及重要的临床试验,并对联合靶向治疗进行了阐述.     

非小细胞肺癌146例诊断来源分析

目的进一步规范非小细胞肺癌的诊断,为其治疗和判断预后提供依据。方法统计2002年2月至2005年8月沈阳军区总医院接受治疗的146例非小细胞肺癌的诊断结果。结果总体有完整病理诊断的123例,占84·2%。其中经手术获得病理诊断的42例,占28·8%;未手术的104例中,经痰细胞学检查、淋巴结针吸活检、胸腔积液细胞学和支气管镜获得诊断的分别为31例(21·2%)、18例(12·3%)、15例(10·3%)和11例(7·5%)。经临床诊断(无明确病理诊断,依据临床体征和影像学检查)的23例,占15·7%。结论在治疗前对非小细胞肺癌作出明确的病理诊断,会使治疗更准确无误,对判定肿瘤的发展和预后更有帮助。     

吉西他滨联合铂类治疗晚期非小细胞肺癌的临床分析

目的评价吉西他滨联合不同铂类化疗药物治疗ⅢB～Ⅳ期非小细胞肺癌（NSCL）的临床疗效和毒副反应。方法45例经细胞学或病理学证实ⅢB～Ⅳ期NSCLC患者（初治35例,复治10例）,患者的预计生存时间均超过2个月。按三种方案联合化疗：（1）吉西他滨＋顺铂（GEM／DDP）,每3周重复1次;（2）吉西他滨＋卡铂（GEM／CBP）,每3周重复1次;（3）吉西他滨＋顺铂（GEM／DDP）,每4周重复1次。按美国癌症研究所（NCI）实体瘤疗效评价标准（Recist标准）对目标病灶评价,毒性反应按2007中国肺癌临床指南（NCI—CTCV2．0）标准进行评价。随访患者中位生存时间并计算1年生存率。结果共完成158个周期全身化疗,平均每个病人接受3．5个周期化疗。吉西他滨联合顺铂3周及4周方案、吉西他滨联合卡铂三种方案的有效率分别为45．8％（11／24）、45．5％（5／11）和50％（5／10）,总有效率为46．7％（21／45）,35例初治患者中有效18例,有效率51．4％,10例复治患者中有效3例,有效率30％。毒副反应主要为白细胞减少、血小板减少、消化道反应、皮疹和搔痒。中位生存时间（MST）为8．9个月,1年生存率为38．7％。结论吉西他滨联合铂类化疗药物治疗晚期NSCL疗效较好,且毒性反应少,耐受性好。     

survivin与非小细胞肺癌关系的研究进展

生存素(survivin)作为一种凋亡抑制因子,具有抑制细胞凋亡和调节细胞分裂双重功能,它通过作用于细胞凋亡途径中的酶促进细胞增殖,参与血管形成,且survivin在大多数肿瘤组织中特别是非小细胞肺癌中表达而在成人正常组织中不表达或低表达.因此无论是通过病理组织还是近几年的对于非小细胞肺癌患者外周血的检测均发现,survivin有望在在非小细胞肺癌的诊断、治疗及预后的评估等方面有广阔的临床应用前景.本文主要综述了实验和临床研究的各种证据,总结survivin与非小细胞肺癌关系的研究进展.