凋亡调节蛋白Fas和Caspase-3在乳腺癌中的表达及意义

目的观察人乳腺癌组织中凋亡调节蛋白Fas和Caspase-3的表达,探讨Fas和Caspase-3与乳腺癌发生、发展的关系。方法收集手术切除的人乳腺癌组织和癌旁相对正常乳腺组织(距癌组织5 cm以上),用免疫组织化学方法对23例乳腺癌标本进行检测。结果在相对正常乳腺组织和乳腺癌组织中Fas蛋白的阳性表达率分别为86.9%和47.3%;乳腺癌组织中Fas的阳性表达率明显低于相对正常乳腺组织。在相对正常乳腺组织和乳腺癌组织中Caspase-3的阳性表达率分别为82.6%和43.5%;乳腺癌组织中Caspase-3的阳性表达率明显低于相对正常乳腺组织。乳腺癌组织中caspase-3与Fas的表达率均与淋巴结转移无关。相关性分析表明,乳腺癌癌中的表达caspase-3与Fas表达呈正相关。结论乳腺癌组织中Fas和Caspase-3表达下调,使肿瘤抗凋亡机制过度激活,可能在乳腺癌的发生和发展过程中起重要作用。     

P53、Fas、FasL在子宫内膜癌放射治疗前后的表达及意义

目的检测P53、Fas、Fasl在子宫内膜癌行放射治疗前后中的表达,探讨其与子宫内膜癌发生发展的关系及为放射治疗提供理论依据。方法采用免疫组化法检测2009年-2012年间在潍坊市妇幼保健院住院治疗的45例子宫内膜癌患者放射治疗前后P53、Fas、Fasl的表达情况。结果（1）P53在子宫内膜癌中的表达放疗后较放疗前减弱,差异有统计学意义（P〈0．05）（2）Fas在子宫内膜癌中的表达放疗后较放疗前增强,差异具有统计学意义（P〈0．05）。（3）Fasl在子宫内膜癌中的表达放疗后较放疗前相差不大,差异无统计学意义（P〉0．05）。结论P53、Fas、Fasl与子宫内膜癌的发生密切相关,术前放疗增加了子宫内膜癌手术疗效。     

乳腺癌淋巴结转移与P53蛋白异常表达的探讨

应用抗P53 抗体和免疫组化染色法检测 35例乳腺癌标本石蜡包埋切片及 19例乳腺组织良性增生病变标本的石蜡包埋切片的P53 蛋白表达 ,结果 35例乳腺癌标本中有 8例呈阳性 ,19例良性病变标本全阴性 .在原发和淋巴结转移配对标本中 ,同一病人不同部位的P53 表达无明显差异 ,提示P53 基因异常发生在肿瘤转移前 ;临床病理发现 ,乳腺癌淋巴结转移与P53 异常表达密切相关 ,检测P53 蛋白的表达可作乳腺癌淋巴结转移的参考指标 .     

乳腺癌淋巴结转移与P53蛋白异常表达的探讨

应用抗P53抗体和免疫组化染色法检测35例乳腺癌标本石蜡包埋切片及19例乳腺组织良性增生病变标本的石蜡包埋切片的P53蛋白表达,结果35例乳腺癌标本中有8例呈阳性,19例良性病变标本全阴性.在原发和淋巴结转移配对标本中,同一病人不同部位的P53表达无明显差异,提示P53基因异常发生在肿瘤转移前;临床病理发现,乳腺癌淋巴结转移与P53异常表达密切相关,检测P53蛋白的表达可作乳腺癌淋巴结转移的参考指标.     

P53调节蛋白ASPPs的分子生物学特性及其与肿瘤的关系

ASPPs(含有富含脯氨酸结构域、锚蛋白重复区及SH3结构域的蛋白)是一类新发现的凋亡调节蛋白,它们能够特异性地调节P53蛋白家族的凋亡活性。ASPPs由ASPP1、ASPP2和iASPP3个同源性很高的成员组成,其中ASPP1、ASPP2可正向调节P53活性,而iASPP的功能恰好与之相反;越来越多的研究表明,此类蛋白功能多样,可参与多条细胞信号通路。ASPPs的异常调控与肿瘤发生、发展密切相关,有望成为肿瘤治疗的新靶点。     

乳腺癌中p53基因缺失及p53蛋白的异常表达

乳腺癌中ｐ５３基因缺失及ｐ５３蛋白的异常表达郭文斌张嘉庆杨德启乔新民张庆广阚秀虞有智一、材料与方法１．材料来源：４７例乳腺癌及正常腺体均来自我院乳腺中心１９９４～１９９６年间手术切除标本。全部病例均有病理学诊断。２．Ｓｏｕｔｈｅｒｎ杂交：用酚、氯仿／...     

Fas—FasL凋亡途径和白血病

Fas受体是TNFR/NGFR超家族成员 ,而Fas配体 (FasL)是TNF/NGF超家族成员。FasL与Fas受体交联 ,转导凋亡信号 ,致靶细胞迅速凋亡。Fas FasL信号转导途径是一独特的凋亡途径。多种白血病细胞表达有Fas受体 ,而FasL主要在CTL细胞上表达 ,因此Fas FasL凋亡途径是机体清除白血病细胞的重要机制之一。Fas FasL凋亡途径异常与白血病的发生、发展、耐药以及缓解后复发有着密切的关系。     

IL-18对系统性红斑狼疮患者淋巴细胞凋亡和P53蛋白表达的影响

目的　研究系统性红斑狼疮 (SLE)患者外周血淋巴细胞在体外IL 1 8刺激培养下细胞凋亡及P53蛋白表达情况。方法　AnnexinV联合PI染色定量法及免疫荧光染色法 ,分析了 44例SLE患者和 30例正常人外周淋巴细胞在体外IL 1 8刺激培养后凋亡发生率 ,凋亡相关基因P53蛋白的表达以及淋巴细胞凋亡发生与疾病活动性的相关性。结果　在IL 1 8刺激培养作用下 ,活动期SLE淋巴细胞凋亡发生率较正常人显著增高 (P <0 .0 1 ) ,而静止期则无明显变化 (P >0 .0 5)。P53蛋白表达在活动期SLE较正常人显著性下降 (P <0 .0 1 ) ,静止期无明显变化 (P >0 .0 5)。P53的表达与疾病活动指数SLEDAI之间有明显的相关性 (P <0 .0 1 )。结论　IL 1 8可引起SLE患者PBL凋亡率的增高 ,表明IL 1 8在体内凋亡或凋亡相关性免疫机制中起着一定的作用     

细胞核和线粒体的P53凋亡途径

与P53介导的细胞周期抑制相比，由DNA损伤、氧化作用以及致癌物引起的P53诱导的细胞凋亡机制还知之甚少，阐明P53肿癌抑制基因诱导凋亡是当务之急，P53作为抗癌靶分子主要在于它的凋亡作用，揭开P53诱导凋亡途径之谜，可以证明P53具有生化多样性，其功能远远超出一个单纯转录因子的功能。线粒体内P53蛋白诱导凋亡的证据表明，协同P53转录活性功能，将使P53诱导的调亡路径变得更加复杂。     

HER-2、P53、Ki-67、Nm23、ER、PR蛋白在乳腺癌中的表达及临床意义

探讨HER-2、P53、Ki-67、Nm23、ER、PR蛋白在乳腺癌组织中表达的特性,同时分析它们之间的相关性和临床意义.应用SP免疫组织化学法检测73例乳腺癌标本中HER-2、P53、Ki-67、Nm23、ER、PR蛋白的表达,并结合其临床和病理资料进行回顾性分析.HER-2、P53、Ki-67、Nm23、ER、PR...     

FasL相关蛋白SH3P12影响FasL细胞膜表达效应研究

目的 研究FasL相关蛋白SH3P12对FasL表达的影响。方法 构建SH3P12真核细胞表达载体，并与FasL共同短暂表达于人胚肾细胞293T细胞。以免疫共沉淀和免疫印迹法确定目的蛋白之间的相互作用，以免疫荧光染色结合激光共聚焦显微镜观察SH3P12与FasL在细胞内表达。结果 在转染的293T细胞中，SH3P12与FasL可形成免疫共沉淀的蛋白-蛋白复合物。荧光蛋白标记结合显微镜观察提示在无SH3P12存在时，FasL主要分布于293T细胞膜，并伴随部分蛋白表达在细胞内高尔基体或内含体样颗粒中；在有SH3P12存在时，FasL与SH3P12形成复合体，共同定位于细胞膜，此时细胞内表达FasL量明显降低。结论 SH3P12为FasL细胞内结合蛋白，其生物学活性可能为稳定FasL在细胞膜上的表达。     

心肌缺血损伤大鼠心肌细胞凋亡与Fas、FasL基因表达的变化

目的探讨异丙肾上腺素(isoprenaline,ISO)诱导的心肌缺血损伤大鼠心肌细胞凋亡与Fas和FasL基因表达变化。方法健康成年SD大鼠随机分为对照组及心肌缺血损伤组(损伤组),腹腔大剂量注射异丙肾上腺素,造成心肌缺血损伤模型。采用原位末端缺口标记(TUNEL)法观察心肌细胞凋亡的改变;应用Western blotting和免疫组化方法检测Fas和FasL蛋白表达的变化,并使用HPIAS10009图像分析仪进行定量分析。结果与对照组比较,缺血损伤组大鼠心肌细胞凋亡率明显增加(P<0.01)、心肌组织Fas、FasL蛋白表达水平显著升高(P<0.01)。结论心肌细胞凋亡及Fas、FasL基因过表达可能参与了心肌缺血损伤的发生和发展。     

P53蛋白在肺癌中表达的研究

应用免疫组化技术,检测了82例原发性肺癌组织标本P53蛋白的异常表达,阳性表达率为53.65％(44/82),其与组织学分型、分级无关。P53蛋白表达与肺腺癌有无局部淋巴结癌转移及患者预后有明显关系(P<0.05),而在肺鳞癌以上各组间差异均无显著性(P>0.05)。提示P53基因突变在肺腺癌、肺鳞癌的演变过程中可能发挥的不同作用。     

Fas/FasL和Bcl-2在人乳腺癌组织中的表达及其与浸润淋巴细胞的关系

目的通过观察乳腺癌组织中凋亡调节蛋白Fas、FasL、Bcl-2的表达及其与肿瘤浸润淋巴细胞(TIL)的关系,探讨Fas、FasL、Bcl-2与乳腺癌发生、发展的关系,为乳腺癌的生物治疗提供实验依据。方法收集手术切除的人乳腺癌组织和癌旁相对正常乳腺组织。用免疫组织化学方法和图像分析技术对21例乳腺癌标本进行检测。结果乳腺癌组织中Fas的阳性表达率明显低于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织中Fas的阳性表达明显低于非浸润性乳腺癌组织(P<0.05);乳腺癌组织中FasL、Bcl-2的阳性表达率明显高于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织明显高于非淋巴细胞浸润性乳腺癌组织(P<0.05);乳腺癌组织中Fas阳性淋巴细胞的数量与相对正常乳腺组织相比明显增多(P<0.05);乳腺癌组织Bcl-2阳性淋巴细胞的数量与相对正常乳腺组织相比明显减少(P<0.05)。结论①乳腺癌组织中Fas表达下调和FasL的过度表达,逃避了免疫监视,诱导Fas敏感的TIL凋亡,从而导致肿瘤的生长;②乳腺癌组织中癌基因Bcl-2过度表达及Bcl-2阳性淋巴细胞的低表达,使肿瘤抗凋亡机制过度激活,肿瘤细胞对Fas/FasL易感性较淋巴细胞相对低,导致TIL死亡,而不是肿瘤细胞死亡。     

Enhanced expression of Fas and FasL modulates apoptosis in the lungs of severe P. falciparum malaria patients with pulmonary edema

Apoptosis mediated by Fas/FasL has been implicated in pulmonary disorders. However, little is known about the relationship between Fas and FasL in the process of lung injury during malaria infection. Paraffin-embedded lung tissues from malaria patients were divided into two groups: those with pulmonary edema (PE) and those without pulmonary edema (non-PE). Normal lung tissues were used as the control group. Cellular expression of Fas, FasL, and the markers of apoptotic caspases, including cleaved caspase-3 and cleaved caspase-8 in the lung tissues were investigated by the immunohistochemistry (IHC) method. Semi-quantitative analysis of IHC staining revealed that cellular expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-3 were significantly increased in the lungs of patients with PE compared with the lungs of patients with non-PE and control groups (all P < 0.05). In addition, significant positive correlations were obtained between Fas and apoptosis (r_s = 0.937, P < 0.001) and FasL and apoptosis (r_s = 0.808, P < 0.001). Significant positive correlations were found between Fas and FasL expression (r_s = 0.827, P < 0.001) and between cleaved caspase-8 and cleaved caspase-3 expression (r_s = 0.823, P < 0.001), which suggests that Fas-dependent initiator and effector caspases, including cleaved caspase-8 and caspase-3, are necessary for inducing apoptosis in the lungs of patients with severe P. falciparum malaria. The Fas/FasL system and downstream activation of caspases are important mediators of apoptosis and may be involved in the pathogenesis of pulmonary edema in severe P. falciparum malaria patients. The proper regulation of the Fas/FasL pathway can be a potential treatment for pulmonary complications in falciparum malaria patients.     

P21 (WAF1) Expression in Colorectal Cancer: Correlation with P53 and Cyclin D1 Expression, Clinicopathological Parameters and Prognosis

P21 (WAF1), P53 and cyclin D1 belong to the cell cycle-regulating family of proteins, and the loss of activity of proteins P53 and P21 (WAF1) seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. The purpose of this study was to assess the relationship between P21 (WAF1), P53 and cyclin D1 immunoreactivity, and to evaluate the prognostic significance of their expression. Tissue sections from 122 paraffin-embedded colorectal carcinomas were immunostained with monoclonal antibodies. Positivity for P21 (WAF1) was found in 48 cases (39%), positivity for P53 in 96 cases (70%) and positivity for cyclin D1 in all the cases (100%). Statistical analyses revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity, as well as an inverse correlation between P21 (WAF1) expression and clinical stage. In univariate analysis, down-regulation of P21 (WAFI) expression was associated with poor prognosis, but multivariate analysis did not confirm its independent prognostic significance. In Cox's analysis only regional lymph node invasion and hepatic metastases were proven as independent prognostic parameters. Our investigation results suggest that in colorectal cancer, the induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. P21 (WAF1), as the main cyclin-dependent kinase (CDK)-inhibitor, may also inhibit the activity of cyclins such as cyclin D1.     

KiSS-1 Expression in Human Breast Cancer

The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using β-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3124±1262 vs 2397±1181) and significantly increased in node positive tumours compared to node negative (3637±1719 vs 2653±1994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4631±3024 vs 2280±1403) whereas expression of the receptor was reduced (480±162 vs 195±134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.     

P16、P53和CyclinD1蛋白在卵巢浆液性肿瘤中的表达及意义

目的 探讨浆液性卵巢上皮性肿瘤中P16、P53和CyclinD1蛋白的表达情况及意义.方法 应用免疫组化法对2010-2011年本院45例浆液性卵巢癌(低级别19例,高级别26例)、25例卵巢交界性浆液性囊腺瘤及21例卵巢浆液性囊腺瘤组织进行P16、P53、CyclinDl蛋白检测,并分析其临床病理意义.结果 P16在良性、交界性与癌组的阳性表达率分别为24％、72％及89％,良性肿瘤组与交界性和癌组之间差异有统计学意义(P＜0.05).P53在良性、交界性与恶癌组的阳性表达率分别为5％、4％及42％,良性和交界性肿瘤组与癌组之间差异有统计学意义(P＜0.05).CyclinD1在良性、交界性与癌组的阳性表达率分别为10％、64％及47％.良性肿瘤组、交界性肿瘤组与癌组之间差异均有统计学意义,P＜0.05.P53、CyclinD1在卵巢浆液性癌高低级间别比较差异均有统计学意义,两者表现为负相关,r=0.211.结论 P16的阳性表达常见于卵巢交界性浆液性囊腺瘤和卵巢浆液性癌中,P53的阳性表达更多见于高级别卵巢浆液性癌中,CyclinD1的阳性表达更多见于卵巢交界性浆液性肿瘤与低级别浆液性癌组织中.卵巢高级别癌与低级别癌的发病机制不同.     

Significance of Fas and FasL protein expression in cardiac carcinoma and local lymph node tissues

Objective: To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of cardiac carcinoma. Methods: Immunohistochemistry was used to detect Fas and FasL protein expression in 64 cardiac carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed. Results: The Fas expression level was significantly higher in normal gastric tissue samples than in cardiac carcinoma tissue samples (85.0% vs. 25.0%, P<0.001), while the FasL expression level was significantly lower in normal gastric tissue samples than in cardiac carcinoma tissue samples (30.0% vs. 81.3%, P<0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs. 56.5%, P<0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated cardiac carcinoma tissue samples (50.0% vs. 18.0%, P=0.015). The FasL expression level was significantly lower in well-differentiated cardiac carcinoma tissue samples than in poorly- differentiated cardiac carcinoma tissue samples (42.9% vs. 84.0%, P=0.021). The Fas and FasL expression levels (25.0% and 81.3%) were significantly different in cardiac carcinoma tissue samples (P<0.001), but had a non-linear correlation (P=0.575). Conclusion: Abnormal Fas and FasL expressions in cardiac carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.