SKP2、p53蛋白在非小细胞肺癌中的表达及其临床意义

目的:研究SKP2、p53蛋白在非小细胞肺癌(NSCLC)组织中的表达特征,探讨它们之间的关系及其对预后的影响.方法:利用组织芯片和免疫组化技术检测SKP2、p53蛋白在89例非小细胞肺癌,10例肺良性病变组织中的表达.结果:NSCLC组织中SKP2、p53蛋白表达阳性率分别为(23.52±13.57)%、( 50.58±24.15)%,均明显高于肺良性病变组织(2.91±1.27)%、(2.83±1.01)%(P=0.000、0.000).SKP2蛋白在NSCLC组织中的表达水平与细胞分化程度,病理类型,TNM分期密切相关(P=0.000,0.000,0.000),而与淋巴转移无统计学联系(P=0.051).p53蛋白在NSCLC组织中的表达水平与病理类型,TNM分期密切相关(P=0.000,0.004),而与细胞分化程度,淋巴转移无统计学联系(P=0.386,0.644).NSCLC组织中SKP2、p53蛋白表达呈正相关(r=0.391,P=0.000),二者同时高表达率20.22%(18/89),与细胞分化程度密切相关(P=0.007),而与病理类型,TNM分期,淋巴转移无统计学联系(P=0.197,0.547,0.302).单因素分析显示SKP2蛋白高表达的NSCLC患者5年生存率较SKP2蛋白低表达的患者降低(P=0.042/0.031);p53蛋白高表达的NSCLC患者5年生存率较p53蛋白低表达的患者无统计学差异(P=0.089/0.154);SKP2、p53蛋白同时高表达的NSCLC患者5年生存率较其他患者明显降低(P=0.015/0.015);多因素分析显示NSCLC患者5年生存率与细胞分化程度,TNM分期,术后放/化疗密切相关.结论:SKP2、p53蛋白在NSCLC的发生发展中起重要作用,且可能存在某种协同作用,但它们对NSCLC患者预后的影响尚需进一步研究.     

肺癌中细胞S期激酶相关蛋白2的表达及其对预后的影响

目的 研究细胞S期激酶相关蛋白2（SKP2）在肺癌中的表达特点及其对肺癌患者预后的影响。方法 利用组织芯片和免疫组化技术,检测SKP2蛋白在89例非小细胞肺癌（NSCLC）、13例小细胞肺癌（SCLC）、5例肺良性肿瘤、5例正常支气管和肺组织中的表达。结果 NSCLC组织中SKP2蛋白阳性率为（23．52±13．57）％,SCLC组织中SKP2蛋白阳性率为（53．85±12．26）％,肺良性肿瘤、正常支气管及肺组织中SKP2蛋白阳性率为（2．91±1．27）％,三者间差异均有统计学意义（P〈0．01）。SKP2蛋白在肺癌中的表达水平与细胞分化程度、淋巴转移及两类肺癌密切相关,差异有统计学意义（P〈0．01）,而与患者年龄、性别、TNM分期等无统计学意义（P值均〉0．05）。生存分析显示,SKP2蛋白表达阳性的肺癌患者5年生存率较SKP2表达阴性的肺癌患者降低（P值均〈0．01）。结论 SKP2蛋白在肺癌组织中的阳性表达明显高于肺良性病变或正常肺组织,尤其在SCLC组织中增高显著,SKP2是影响肺癌患者预后的一个独立因素。     

非小细胞肺癌组织COX-2和p53表达及其临床意义的探讨

目的:探讨COX-2 和突变性p53蛋白在非小细胞肺癌(NSCLC)发生、发展中的作用机制及两者之间的相关性.方法:流式细胞仪检测80例NSCLC组织和20例癌旁正常肺组织中COX-2 蛋白、突变型p53蛋白的表达情况.结果:NSCLC组织中COX-2蛋白较正常组织高表达,P<0.01.COX-2表达与有无淋巴结转移(P=0.002)和肿瘤大小(P=0.045)有关,与NSCLC患者性别、TNM分期、分化程度和组织学类型无关,P>0.05.NSCLC组织中p53蛋白较正常组织高表达,P<0.01.p53蛋白表达与有无淋巴结转移(P=0.01)有关;而与NSCLC患者性别、肿瘤的大小、TNM分期、肿瘤分化程度和组织学类型无关,P>0.05.NSCLC组织中p53和COX-2蛋白同时阳性表达率为47.82%(22/46),p53阴性COX-2蛋白阳性表达率为58.82%(20/34),两者表达无相关性,P=0.33.结论:COX-2的过表达及p53蛋白突变与NSCLC的发生发展有关,两者之间无相关性.     

非小细胞肺癌组织Livin和Smac蛋白表达及其临床意义的研究

目的:探讨Livin和Smac蛋白在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达及其对NSCLC患者预后的影响.方法:用免疫组织化学技术检测Livin和Smac蛋白在89例NSCLC组织和25例癌旁肺组织中的表达.结果:NSCLC组织中Livin和Smac蛋白阳性表达率分别为53.9%(48/89)和58.4%(52/89),高于癌旁肺组织中的8.0%(2/25)和12.0%(3/25),差异有统计学意义,x2值分别为16.723和16.848,P值均为0.000.Livin和Smac蛋白表达密切相关,x2=18.451,P=0.000,r=0.455.Livin蛋白表达水平与淋巴结转移、TNM分期及病理类型密切相关,x2值分别为19.433、17.161和7.772,P值分别为0.000、0.000和0.021;与性别、年龄、分化等无关,P均>0.05.Smac蛋白表达水平与淋巴结转移、TNM分期密切相关.x2值分别为7.748和7.064,P值分别为0.005和0.008;与性别、年龄和病理类型等无关,P均>0.05.Kaplan-Meier法分析显示,Livin蛋白表达阳性组的预后较阴性组差,x2=7.407,P=0.006;而Smac蛋白表达与预后无关,x2=0.945,P=0.331.结论:Livin蛋白表达与NSCLC的发生、发展密切相关,并对患者的预后产生不良影响.Smac蛋白表达与NSCLC的发生、发展相关,但与预后无关.Livin有可能成为评估NSCLC进展和预后的有价值指标.     

非小细胞肺癌组织中SKP2蛋白的表达及其对预后的影响

目的:探讨SKP2蛋白在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其对患者预后的影响。方法:利用组织芯片和免疫组化技术检测SKP2蛋白在89例NSCLC、5例肺良性肿瘤和5例正常支气管和肺组织中的表达。结果:NSCLC组织中SKP2蛋白表达阳性率为(23·52±13·57)%,明显高于肺良性肿瘤、正常支气管及肺组织(2·91±1·27)%,两者差异有统计学意义,t′=31·373,P=0·000。SKP2蛋白在NSCLC组织中的表达水平与细胞分化程度密切相关,χ2=14·402,P1=0·000;与年龄、性别、吸烟史、肿瘤位置、大小、病理类型、淋巴结转移和TNM分期等差异无统计学意义,P1值均>0·05。SKP2蛋白表达阳性的NSCLC患者5年生存率较阴性患者降低,χ2=4·119/4·636,P1=0·042/0·031;r=-0·186,P2=0·000。结论:SKP2蛋白表达在NSCLC的发生发展中起促进作用,并对患者的预后产生不良影响。     

非小细胞肺癌组织p53基因家族成员的不同表达及意义

目的探讨p53基因家族成员p53、p63和p73在非小细胞肺癌(NSCLC)中的不同表达及其临床意义.方法利用免疫组化S-P法在60例NSCLC和7例正常肺组织中检测p53、p63和p73蛋白的表达.结果在NSCLC中,p53、p63和p73蛋白的阳性表达率分别为61.67%(37/60)、80.00%(48/60)和73.33%(44/60);与正常肺组织相比,p53、p63和p73蛋白阳性表达率的差异均有显著性(P＜0.05).p53蛋白表达与肺癌细胞分化程度有密切关系(P=0.023),而与组织学类型、淋巴结转移和临床分期均无明显关系(P＞0.05).p63蛋白表达与肺癌组织学类型(P=0.001)和淋巴结转移(P=0.028)有密切关系,而与细胞分化程度和临床分期无明显关系(P＞0.05).p73蛋白表达与肺癌的临床病理特征均无明显关系(P＞0.05).在NSCLC中,p63和p73蛋白表达之间呈显著正相关(P=0.000 1),p73与p53蛋白表达之间无显著相关性(P＞0.05).结论p53基因家族可能与NSCLC的发生发展有关.p63和p73蛋白有不同于p53蛋白的生物学功能,二者可能均起癌基因的作用.     

Survivin、P53、Bcl-2蛋白与非小细胞肺癌临床病理因素的关系

目的探讨survivin、p53、Bcl-2蛋白在非小细胞肺癌(NSCLC)中的表达及与临床病理因素的关系。方法应用免疫组织化学法(SP)检测80例NSCLC肿瘤组织、20例肺良性病变组织中survivin、p53、Bcl-2蛋白表达情况。结果survivin、p53、Bcl-2蛋白在肺癌组织中的阳性表达率分别为61.3%(49/80)、55.0%(44/80)和50.0%(40/80),高于肺良性病变组织中的表达水平(P<0.05)。survivin蛋白的表达在不同的TNM分期之间有显著性差异,但与肺癌组织的细胞类型、分化程度及淋巴结转移无明显关系;P53蛋白的表达在不同的淋巴结转移情况之间以及在不同的TNM分期之间有显著性差异;Bcl-2蛋白的表达在不同的细胞类型之间有显著性差异(P<0.05)。肺癌组织中p53,Bcl-2蛋白与survivin蛋白表达显著相关(P<0.05)。结论survivin、P53、Bcl-2蛋白与肺癌的发生和发展密切相关,并可能起协同作用,其综合检测对肺癌的病情判断和预后评价具有一定价值。     

Survivin、p53、Bcl-2蛋白在非小细胞肺癌中的表达及意义

目的:探讨Survivin基因在非小细胞肺癌(NSCLC)中的表达,以及与P53,Bcl-2蛋白表达的相互关系。方法:应用免疫组织化学法(SP)检测80例NSCLC肿瘤组织、20例肺良性病变组织中Survivin蛋白、P53蛋白、Bcl-2蛋白表达情况,并将结果进行了相关分析。结果:Survivin蛋白在肺良性病变组织中不表达,在61.3%(49/80)的NSCLC组织中有表达,且Survivin的表达与肺癌患者的TNM分期有关,但与肺癌的细胞类型、分化程度及淋巴结转移无明显关系;肺癌组织p53蛋白阳性表达率55.0%(44/80),与肺癌的TNM分期及淋巴结转移有关,肺良性病变组织中无p53蛋白表达;肺癌组织Bcl-2蛋白阳性表达率50.0%(40/80)明显高于肺良性病变组织的10.0%(2/20),其中鳞癌组织的表达率62.2%,明显高于腺癌组织的表达率34.3%(P<0.05);肺癌组织中P53,Bcl-2蛋白与Survivin蛋白表达显著相关(P<0.05)。结论:Survivin蛋白在肺癌组织中表达上调,提示该基因对NSCLC的发生发展起重要作用。Survivin基因有望成为肺癌基因治疗的新靶点;Survivin蛋白表达与肺癌的TNM分期密切相关,提示可作为判断病情和评价预后的指标。Sur vivin蛋白的表达与p53蛋白、Bcl-2蛋白的表达均呈正相关,三者在肺癌的发生中可能起协同作用。     

肺癌中p53和p63 蛋白表达的高通量组织微阵研究

目的探讨p53和p63蛋白在肺癌中的表达及意义,并比较两者之间的表达关系.方法组织微阵(tissue microarray,TMA)技术和免疫组化S-P方法(immunohistochemistry,IHC).结果p53蛋白IHC染色中,TMA有价值的肿瘤标本为234(72.9%),总的表达率(+、++、+++)率为48.3%(113/234).随着肺鳞状细胞癌(squamous cell carcinoma,SCC)和腺癌(adenocarcinoma,Ad)分级升高,p53蛋白表达增强,与肺SCC及Ad病理分级有明显相关性(P＜0.05).p53蛋白表达与生存期呈明显负相关性(P＜0.05).p53蛋白表达与病理分型和临床分期等无明显相关性(P＞0.05).p53蛋白表达在肺癌原发肿瘤和转移淋巴结之间无明显差异(P＞0.05).p63蛋白IHC染色中,TMA有价值的肿瘤标本为264(82.2%),总的表达率(+、++、+++)为67.8%(179/264).p63蛋白在小细胞肺癌(small cell lung carcinoma,SCLC)表达最低16.0%(4/25),非小细胞肺癌(non-small cell lung carcinoma,NSCLC)与SCLC之间表达存在明显差异(P＜0.05).p63蛋白表达与病理组织分级、临床分期、生存期等无明显相关性(P＞0.05).p63蛋白表达在肺癌原发肿瘤和转移淋巴结之间无明显差异(P＞0.05).结论1.p53是肺癌的独立预后指标;2.p63蛋白在肺癌的不同病理类型的不同表达,说明肺癌的不同病理类型分子机理有所不同;3.p53蛋白和p63蛋白表达之间无明显相关性;4.TMA可以有效分析比较组织中肿瘤标记物的表达情况.     

肺癌组织中雌激素受体α和雌激素受体β的表达及临床意义

目的 研究雌激素受体α(ERα)和雌激素受体β(ERβ)在肺癌组织中的表达及与患者临床病理特征和预后的关系.方法 将698例肺癌石蜡标本构建组织芯片,其中非小细胞肺癌(NSCLC)651例(包括腺癌309例,鳞癌342例),小细胞肺癌(SCLC)47例.采用免疫组化法检测ERα和ERβ蛋白在肺癌组织和正常肺组织中的表达,并分析ERα和ERβ蛋白的表达与NSCLC患者临床病理特征和预后的关系.结果 ERα和ERβ蛋白在正常肺组织中的阳性表达率分别为0和25.0％.ERα蛋白在腺癌、鳞癌和SCLC组织中的阳性表达率分别为70.8％ (209/295)、51.2％ (169/330)19.1％ (9/47),差异有统计学意义(P＜0.001).ERβ蛋白在腺癌、鳞癌和SCLC组织中的阳性表达率分别为67.3％ (200/297)、43.5％(140/322)和66.0％ (31/47),差异有统计学意义(P＜0.001).ERα蛋白的表达与NSCLC患者的吸烟史、病理分期和淋巴结转移有关(均P＜0.05),而与性别、年龄、肿瘤大小和分化程度无关(均P＞0.05).ERβ蛋白的表达与患者的性别、吸烟史、病理分期和淋巴结转移有关(均P ＜0.05),而与患者的年龄、肿瘤大小和分化程度无关(均P＞0.05).398例NSCLC患者完成随访,ERα和ERβ蛋白在不同分期和不同组织类型NSCLC中的表达均与患者的预后无关(均P ＞0.05).结论 ERα和ERβ蛋白在肺腺癌、鳞癌和SCLC组织中的表达存在明显差异.在NSCLC中,ERα和ERβ蛋白的表达与吸烟、病理分期、淋巴结转移均有关,且女性NSCLC患者ERβ蛋白的表达高于男性.     

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.