Fas，FasL和cFLIP与宫颈癌研究现状

脂肪酸合成酶（Fas）是一种跨膜蛋白,属于肿瘤坏死因子（TNF）超家族。其与配体（FasL）相互作用是诱导细胞凋亡的主要途径之一。研究表明,Fas／FasL异常表达可引起肿瘤组织中细胞凋亡与增殖失衡。细胞型Fas相关死亡结构域蛋白样白细胞介素-1β转换酶抑制蛋白（cFLIP）是一种内源性凋亡抑制蛋白．可抑制多种凋亡受体。如Fas／FasL等诱导的细胞凋亡。近来发现,Fas/FasL、cFLIP在许多肿瘤组织中表达异常,可作为肿瘤治疗新靶点。已开展对三者在宫颈癌中的相关研究,将为宫颈癌诊断、治疗及预后判断提供新思路和手段。     

非小细胞肺癌组织中cFLIP和P53蛋白的表达

目的探讨非小细胞肺癌（NSCLC）组织中cFLIP、P53蛋白的表达及意义。方法采用免疫组化方法检测56例NSCLC组织和16例肺良性病变中cFLIP、P53蛋白表达情况，分析二者在肺癌组织学分型、分化程度、临床分期和淋巴结转移方面表达差异及其相关性。结果56例NSCLC标本中cFLIP和P53阳性表达率分别是58．9％（33／56）、62．5％（35／56），肺良性病变组织标本中阳性率分剐是18．75％（3／16）和0％。cFLIP和P53在Ⅰ、Ⅱ期、无淋巴结转移组中的表达分别低于Ⅲ、Ⅳ期和淋巴结转移组，而在病理组织学分型和不同分化组间无统计学意义。cFLIP和P53在肺癌组织中的表达呈正相关（r=0．328，P〈0．05）。结论cFLIP和P53可以作为肺癌预后的评价指标，P53对cFLIP的表达可能有调控作用。     

Differential effect of storage on molecular and ultra-molecular dilutions of histamine

Objectives and design:  In this study, we examine the relationship between C5a and activation of cysteine aspartic acid protease 8 (caspase 8) in human umbilical vein endothelial cells (HUVEC). Materials or subjects:  Primary cultures of HUVEC were used. Treatments:  Recombinant human C5a (50 ng/ml) was used in the presence or absence of 10 μg/ml cycloheximide (CHX). Methods:  HUVEC were treated with C5a alone and in the presence of CHX, then monitored for cell viability, poly- ADP-ribose 1 (PARP-1) and caspase 8 activities. Gene and protein expressions were assessed for caspase 8 and the caspase 8 homologue, FLICE –inhibitory protein (cFLIP). Results:  We found a 43.1 ± 6.9 percent reduction in viability of HUVEC stimulated for 18 h with 50 ng/ml C5a in the presence of 10 μg/ml CHX (p < 0.05). In contrast, the cell viability of cells stimulated for 18 h with 50 ng/ml C5a or 10 μg/ml CHX alone was not significantly different compared to the non-stimulated control. Treatment of HUVEC with C5a induced an increase in caspase 8 activity but did not significantly affect cFLIP levels. Conclusions:  These data suggest caspase 8 activation induced by C5a leads to cell death if protein synthesis of antiapoptotic protein(s) is blocked. Received 23 July 2008; returned for revision 10 September 2008; received for final revision 29 September 2008; accepted by M. Parnham 18 September 2008     

cFLIP反义寡核苷酸抑制结肠癌细胞SW620的增殖

目的 研究cFLIP反义寡核苷酸(cFLIP-asODN)对人结肠癌细胞株SW620细胞增殖的影响.方法 利用脂质体将cFLIP-asODN转染入SW620细胞,并设空载体+cFLIP-asODN转染组、脂质体+无意义ODN转染组和空白对照组作为对照.荧光倒置显微镜检测复合物对细胞的转染效率;荧光实时定量RT-PCR和...     

Cellular (FLICE) like inhibitory protein (cFLIP) expression in diffuse large B-cell lymphoma identifies a poor prognostic subset, but fails to predict the molecular subtype

Immunohistochemistry can sub‐classify diffuse large B‐cell lymphoma (DLBCL) into germinal centre B‐cell like (GCB) and non‐GCB subtypes. The latter consists predominately of the activated B‐cell like subgroup in which nuclear factor kappa‐B activation is its characteristic. Expression of cellular caspase 8 (FLICE)‐like inhibitory protein (cFLIP), a caspase 8 homologue, is regulated by nuclear factor kappa‐B signalling, and it is the main inhibitor of Fas ligand activated apoptosis. To determine if cFLIP expression was confined to non‐GCB subtype, we studied 66 cases of DLBCL. cFLIP expression showed no significant correlation to DLBCL subtypes (GCB or non‐GCB) but was associated with a worse clinical outcome. For cFLIP positive and negative patients, the five‐year event free survival was 20 and 31%, respectively (p = 0.049), and the five‐year overall survival was 20 and 57%, respectively (p = 0.041). Copyright © 2011 John Wiley & Sons, Ltd.     

Differential Expression of Intracellular Apoptotic Signaling Molecules in Tumor and Tumor-Infiltrating Lymphocytes During Development of Invasion and/or Metastasis of Gastric Carcinoma

The presence and functional status of intracellular expression of caspase 8, caspase 10, cFLIP, caspase 3, survivin, and NF-kappaB was investigated in permeabilized tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (N = 20) from primary locus, metastatic gastric carcinoma (N = 22) from malignant ascites, and benign gastric mucosa (N = 20) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the six intracellular molecules were constitutively expressed in primary and metastatic carcinomas as well as normal epithelium in nearly all the patients. In particular, metastatic carcinoma revealed to significantly overexpress these molecules. In the analysis of TIL, the expression of these six molecules could usually be observed in carcinoma and normal epithelium. There was aberrant expression of these molecules in immune TIL within metastatic carcinoma nests. Taken together, the results showed the significantly different expression of the signaling molecules in both tumor and TIL between primary and metastatic carcinoma nests. Increased expression of cFLIP, survivin, and NF-kappaB in carcinoma might play an important role in hindering an intracellular apoptotic process, followed by accelerating the cancer invasion and/or metastasis.     

Fas、FasL及cFLIP在宫颈病变中的表达与宫颈癌发生发展相关性的初步探讨

背景与目的:虽然机体有一系列免疫监视机制,但肿瘤仍能发生并持续发展。本研究通过检测Fas、Fas配体(FasL)、cFLIP在宫颈癌及宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)中的表达,探讨其在宫颈癌发生发展中作用。方法:应用免疫组织化学染色的方法,检测40例宫颈癌、20例CIN及20例正常宫颈上皮中Fas、FasL和cFLIP的表达,并进行相关临床病理因素分析。结果:Fas在宫颈癌和CIN中的阳性表达率(47.5%,45.0%)明显低于在正常宫颈组织的表达率(90.0%,P<0.05),其阳性表达率的高低与CIN的分级、临床分期及组织学分级有关(P<0.05);FasL在宫颈癌和CIN中的表达率(50.0%,40.0%)则明显高于正常宫颈组织中的表达率(5.0%,P<0.05),其阳性表达率的高低与CIN的分级,临床分期,及组织学分级有关(P<0.05),且有淋巴结转移者明显高于无淋巴结转移者(P<0.05);cFLIP在宫颈癌和CIN中的表达率(92.5%,70.0%)明显高于在正常宫颈组织中的表达率(10.0%,P<0.05),cFLIP的表达与CIN的分级有关(P<0.05),与宫颈癌的临床分期、组织学分级、病理类型、淋巴结是否转移无关(P>0.05)。Fas与FasL的表达呈负相关(ra=-0.69,P<0.05),cFLIP与Fas的表达密切相关(ra=0.368,P<0.05)。结论:宫颈癌细胞通过Fas低表达和FasL、cFLIP高表达逃避机体免疫监视并进行免疫反击以促使肿瘤发生、发展及转移。     

胃腺癌组织中cFLIP mRNA的表达及细胞凋亡检测

目的:检测胃腺癌组织中cFLIP mRNA的表达及胃腺癌细胞的凋亡.方法:采用原位杂交技术检测45例胃腺癌、23例癌旁不典型增生及21例正常胃黏膜组织中cFLIP mRNA的表达;运用TUNEL法检测胃腺癌细胞凋亡情况,计算凋亡指数(AI).结果:胃腺癌组织中cFLIP mRNA的阳性表达率高于正常黏膜及不典型增生组织...