肝细胞癌细胞凋亡相关蛋白bcl-2和bax的表达及意义

目的:探讨原发性肝细胞癌(简称肝癌)细胞凋亡相关蛋白bcl-2和bax的表达情况及其意义.方法:采用免疫组化ABC法检测bcl-2和bax蛋白在66例人肝癌组织和24例人正常肝组织,以及3种人肝癌细胞系HCC-9204、SMMC-7721、HHCC和1种人正常肝细胞系QZG的表达情况,并分析肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间的关系.结果:bcl-2蛋白在正常肝组织中表达的阳性率只有4.2 %(1/24),在肝癌组织中的阳性率为25.8 %(17/66),二者具有显著性差异(P＜0.05).bax蛋白在正常肝组织中表达的阳性率为70.8 %(17/24),在肝癌组织中的阳性率为43.9 %(29/66),二者也具有显著性差异(P＜0.05).肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间均未见明显的相关性.在正常肝和肝癌组织中,bcl-2蛋白的阳性率均明显低于bax蛋白(P＜0.01,P＜0.05).在正常肝细胞系QZG中未见明显的bcl-2阳性信号,bax蛋白的阳性细胞计数率为61.0%.肝癌细胞系SMMC-7721和HHCC的bcl-2蛋白阳性细胞计数率分别为14.3%和11.8%,bax蛋白阳性细胞计数率分别为58.3%和47.1%.肝癌细胞系HCC-9204中未见明显的bcl-2阳性信号,bax蛋白阳性细胞计数率为43.2%.结论:与正常肝组织相比,肝癌组织可出现bcl-2蛋白表达低度升高,bax蛋白表达下降.正常肝和肝癌组织的bcl-2蛋白表达水平均低于bax蛋白.肝癌和正常肝细胞系的bcl-2蛋白表达水平很低,可见中等程度的bax蛋白表达.     

肝癌细胞及正常肝细胞中间隙连接蛋白Cx32、Cx43的表达--激光扫描共聚焦显微镜研究

目的研究间隙连接蛋白Cx32、Cx43在肝癌细胞系HHCC、SMMC-7721及正常肝细胞系QZG中的表达.方法采用免疫荧光标记技术,对HHCC、SMMC-7721及QZG细胞中Cx32、Cx43蛋白进行激光扫描共聚焦显微镜(LSCM)分析.结果Cx2、Cx43蛋白定位于肝细胞胞质中,在HHCC、SMMC-7721中阳性细胞率、阳性细胞的荧光强度较QZG中明显减弱.结论Cx32、Cx43蛋白表达降低可能与肝细胞癌的发生有关.     

肝细胞癌HLA—DR抗原的研究及意义

目的：探讨人白细胞DR抗原(HLA-DR)在人原发性肝细胞癌(简称肝癌)的表达情况及其意义。方法：分别采用免疫组化ABC法和流式细胞仪检测了HLA-DR在46例人肝癌组织和4种培养的人肝癌细胞系(SMMC-7721、HCC-9204、BEL-7402和HHCC)的表达情况。结果：39.1％(18／46例)的肝癌组织癌细胞可表达HLA-DR,而在癌旁非肿瘤细胞为阴性。4种肝癌细胞系都基本上不表达HLA-DR。结论：肝癌组织可在一定程度上表达HLA-DR,但是培养的肝癌细胞系基本上不表达。HLA—DR与肝癌发生、发展的关系及其在抗肝癌免疫应答中的作用有待进一步研究。     

HLA-DR抗原在培养的肝细胞癌细胞表面的表达及意义

HLA-DR是人类MHCⅡ类分子的主要类型之一,在机体免疫应答及免疫调节过程中发挥着重要的作用.MHCⅡ在肿瘤细胞的表达主要表现为其主要类型HLA-DR的表达,并且其阳性率与多种肿瘤的分化程度和预后密切相关.但是关于HLA-DR在培养的原发性肝细胞癌细胞表面的表达情况尚未见报道.本文采用对生长于盖玻片上的贴壁培养细胞进行免疫组化ANC法染色,检测了HLA-DR在HHCC、SMMC-7721、BEL-7402和HCC-9204等4种培养的人肝细胞癌细胞系以及正常人肝细胞系QZG表面的表达情况.阳性肝癌细胞呈现棕黄染色.如果>5%左右的肝癌细胞为阳性,则认为该种细胞阳性,否则为阴性.两人双盲法阅片,观察结果一致.结果表明,4种肝癌细胞中只有部分SMMC-7721细胞表面呈阳性,多次实验的结果经多个样本率的X~2检验,具有显著差异(P<0.05).阳性肝癌细胞着色略呈细颗粒状,阳性信号普遍较弱,HLA-DR在QZC细胞表面未见表达.说明HLA-DR可以在某些培养的肝细胞癌细胞系中表达.     

原发性肝细胞癌细胞凋亡相关蛋白bcl—2和bak的表达及意义

目的探讨细胞凋亡相关蛋白bcl-2和bak与肝癌的关系及其意义.方法采用免疫组化S-P方法,检测22例肝癌、22例肝癌伴肝硬变、20例肝硬变和10例正常肝组织中bcl-2及其相关蛋白bak的表达.结果 bcl-2蛋白在肝癌中表达阳性率为50.0%(22/44),而正常肝组织为60.0%(6/10),差异有显著性(P<0.05).在肝癌组织中bak蛋白表达阳性率为88.6%(39/44),而肝硬变组织为95.0%(19/20),差异无显著性(P>0.05).结论 bcl-2在肝癌和肝硬变组织呈中等表达,而bak在肝癌和肝硬变均呈高表达.     

乙醇诱导肝癌细胞凋亡及其相关蛋白的研究

目的探讨乙醇对肝细胞癌(简称肝癌)细胞凋亡的诱导作用,并对其相关蛋白的表达进行初步分析。方法用含6%乙醇的培养液培养6h诱导肝癌细胞系HCC-9204细胞凋亡,进行台盼蓝染色、Hoechst33258荧光染色、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测和流式细胞仪DNA含量分析。SDS-PAGE电泳分析诱导凋亡前后的细胞蛋白表达的情况。结果6%乙醇可使HCC-9204细胞产生明显的凋亡形态学变化。大部分细胞呈台盼蓝拒染,并且为TUNEL阳性着色。流式细胞仪分析可见亚二倍体凋亡峰。SDS-PAGE电泳显示,乙醇诱导凋亡的HCC-9204细胞中有新的分子量约大于97.4kD的蛋白产生。结论低剂量乙醇能够明显地诱导HCC-9204肝癌细胞凋亡,并且可使其产生新的大分子量蛋白质。     

新基因pp3774的亚细胞定位以及在肝癌细胞系和组织中的表达谱研究

目的探讨新基因pp3774在肝癌细胞系、人肝癌及癌旁肝、肝硬化以及正常肝组织中的表达差异及其生物学功能.方法脂质体转染-荧光观察pp3774-GFP融合蛋白的亚细胞定位;合成新基因pp3774特异性多肽,制备兔源性多克隆抗体;用RT-PCR、蛋白印迹、免疫细胞化学及免疫组化方法检测pp3774基因在7个肝癌细胞系及214例肝细胞癌、18例肝硬化及10例正常肝组织中的表达差异.流式细胞术检测转染pp3774基因的SMMC-7721细胞的凋亡率.结果 pp3774蛋白主要定位于细胞质(内质网为主);RT-PCR检测结果表明pp3774 mRNA在肝癌细胞系BEL-7402、Huh-7、MHCC-97L及HepG2中高表达,SMMC-7721、MHCC-LM3及人永生化肝细胞系L-02中度表达,而在Hep3B中低表达;肝癌及癌旁组织中pp3774 mRNA的表达表现为癌旁高于癌(P<0.05);免疫组化结果显示pp3774蛋白表达程度依次为正常肝≥肝硬化≥癌旁肝组织>肝癌.转染pp3774基因的SMMC-7721细胞的凋亡发生率高于对照组约10%.结论 pp3774基因是一个具有抑制肝癌细胞生长功能的新基因.     

bcl-2和bax蛋白表达与鼻咽癌放射敏感性相关关系的探讨

目的:探讨bcl-2和bax蛋白的表达与鼻咽癌放射敏感性的关系.方法:应用免疫组化法检测51例放疗前鼻咽癌活检组织中bcl-2和bax蛋白的表达.结果:51例鼻咽癌组织中bcl-2和bax蛋白表达阳性者均为47例(92.2%);鼻咽癌组织中bcl-2和bax蛋白的表达强度呈显著相关(P＜0.05);bcl-2蛋白的表达与鼻咽癌放射敏感性呈负相关(P＜0.05),而bax蛋白的表达与鼻咽癌放射敏感性无关(P＞0.05);bcl-2/bax的比率与鼻咽癌放射敏感性呈负相关(P＜0.05).结论:bcl-2蛋白和bcl-2/bax的比率是反映鼻咽癌放射敏感性和预测鼻咽癌放疗效果的重要指标,而bax蛋白不能单独作为判断鼻咽癌放射敏感性的指标.     

bcl-2基因在胃癌和肝癌中的表达及意义

bcl-2基因及其家族作为重要的凋亡调控基因在多种肿瘤中得到研究.胃癌细胞中可能并不出现理论上的bcl-2表达增加,bax表达下降,而是存在恰好相反的情况.bcl-2在肠型胃癌中的表达高于弥漫型胃癌,在胃癌的早期发生及表型分化方面起着重要作用.肝癌中bcl-2蛋白表达水平上调和bax蛋白表达水平下降导致bax/bcl-2比例下调,在肝癌发生过程的调控中可能具有一定的意义,并且可能与肝胆管癌发生有关,而在肝细胞癌发生过程中的作用有限,bcl-2和bax蛋白表达的阳性率与肝癌病理分级之间均未见明显的相关性.     

TC21/R-Ras 2在肝癌中的表达、亚细胞定位及意义

目的:探讨TC21基因在肝癌细胞、肝癌及癌旁组织中的表达、亚细胞定位及意义。方法:用RT-PCR检测TC 21在肝癌细胞系及人肝癌及癌旁组织中mRNA水平的表达,用免疫组化及Western印迹检测TC21蛋白在肝癌相关组织中的表达差异,用组织芯片技术结合免疫组化检测TC21蛋白的亚细胞定位。结果:RT-PCR检测结果表明TC21 mRNA在SMMC-7721、BEL-7402、Huh-7、Hep3B、HepG2、MHCC-97L、MHCC-LM3 7个肝癌细胞系及L-02和Chang liver 2株永生化人肝细胞系、7对肝癌及对应癌旁肝组织中均有较高表达;Western印迹结果表明上述细胞系中TC21蛋白表达与mRNA表达一致,TC21在4对肝癌及癌旁组织中均呈较高水平的表达;免疫组化检测结果表明TC21在人原发性肝癌、癌旁组织、硬化肝组织与正常肝组织中的表达阳性率分别为84.2%、77.2%、41.7%、0%,肝癌与肝硬化、正常肝相比显著高表达(P<0.05,P<0.01),与癌旁组织比无统计学意义(P>0.05);统计学分析结果表明TC21蛋白表达与肿瘤大小呈正相关(P<0.05),与是否肝硬化呈负相关(P<0.05);肝癌组织中TC21主要定位于肝癌细胞核,部分定位于胞质,膜定位不明显,TC21蛋白在肝癌细胞中的核定位显著高于癌旁肝细胞(P<0.001)。结论:本研究首次揭示TC21蛋白在肝癌组织中的高表达及核定位预示其在肝细胞恶性转化及肝癌发生发展中发挥重要作用。     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.