乳腺癌中RUNX3、cyclin D1和p27kip1蛋白的表达及其意义

[目的]探讨乳腺癌组织中RUNX3、cyclinD1和p27^kip1基因的表达及其临床意义。[方法]采用免疫组织化学SP法检测88例乳腺癌、40例乳腺纤维腺瘤、40例乳腺增生病中RUNX3、cyclinD1和p27^kip1的表达。[结果]（1）RUNX3和p27^kip1在乳腺癌中的阳性表达率分别为35．23％和51．14％，明显低于在乳腺纤维腺瘤（85％和82．5％）及乳腺增生病（87．5％和85％）中的表达率（P〈0．05）。乳腺癌中cyclinD1的表达率（63．63％）明显高于良性病变中表达。（2）RUNX3和p27^kip1蛋白表达与乳腺癌的临床分期、淋巴结转移呈负相关。p27^kip1蛋白表达与病理分级呈负相关。cyclinD1蛋白表达与病理分级呈正相关。（3）乳腺癌中RUNX3与p27^kip1蛋白的表达呈正相关性（P〈0．05）．与cyclinD1的表达呈负相关性（P〉0．05）。[结论]RUNX3、cyclinD1和p27^kip1在乳腺癌的发生发展中起重要作用。检测乳腺癌组织中RUNX3、cyclinD1和p27^kip1基因的表达对于评价患者的预后有一定价值。     

skp2、p27kip1在正常胃黏膜和胃癌组织中的表达

[目的]探讨细胞S相激酶相关蛋白2（skp2）和细胞周期素依赖性激酶抑制蛋白27（p27^kip1）表达与胃癌发生的关系。[方法]用免疫组化SP法检测69例胃癌组织中skp2、p27^kip1蛋白的表达，并与28例正常胃黏膜作对比；用RT-PCR方法随机检测其中3例胃癌组织中skp2的mRNA表达，并与其正常胃黏膜作对比。[结果]p27^kip1蛋白阳性表达率在胃癌中为46.38％，而正常胃组织中为96．43％（P〈0．00。p27^kip1蛋白在胃癌中的阳性表达率随肿瘤分化程度的降低、浸润深度的加深、淋巴结转移、病理分期进展而降低（10〈0．05）。skp2 mRNA在胃癌组织中的表达明显上凋（P〈0．01）。skp2蛋白阳性表达率在胃癌中为33.33％，而正常胃组织中为10．71％（P〈0．05）。skp2蛋白阳性表达率随肿瘤的分化程度降低而升高fP〈0．05）。skp2、p27^kip1蛋白在胃癌中的表达呈负相关（P〈0．01）。[结论]p27^kip1、skp2蛋白检测有助于胃癌的临床诊断及判断预后。     

人脑胶质瘤中凋亡相关基因survivin和p53的表达研究

目的探讨凋亡相关基因survivin和p53在人脑胶质瘤发生发展中的作用及其相互关系。方法采用免疫组化S-P法检测10例正常脑组织及75例脑胶质瘤标本中survivin、p53的表达情况并分析二者之间的关系。结果survivin在正常对照组和胶质瘤组中的阳性表达率为0％和45．3％，差异有显著性（P〈0．05）。胶质瘤Ⅰ级、Ⅱ级和Ⅲ，Ⅳ级，survivin的阳性表达率分别为15．0％、33．3％、74．2％，差异有极显著性（P〈0．001）。p53在正常脑组织和人脑胶质瘤组织中阳性表达率为0％和41、3％，差异有显著性（P〈0．05）。胶质瘤Ⅰ级、Ⅱ级和Ⅲ-Ⅳ级，p53的阳性表达率0％、41．7％、67．7％，差异有极显著性（P〈0．001）。75例胶质瘤组织中survivin与p53共阳性23例，共阴性33例，二者的表达呈正相关（rs=0．438，P〈0．01）。结论1）survivin的阳性表达率随胶质瘤恶性程度而升高；2）突变型p53蛋白的活性表达与肿瘤的组织病理类型、分化程度有关，p53基因的突变参与脑胶质瘤的发生发展；3）p53的突变与survivin的激活在胶质瘤的发生发展中可能起协同作用。     

人脑胶质瘤组织p57^kip2和P16蛋白表达及其临床意义的研究

目的：探讨p57^kip2蛋白、p16蛋白在人脑胶质瘤组织中的表达及其临床意义。方法：采用免疫组织化学SP法检测p57^kip2、p16在55例人脑胶质瘤和10例正常脑组织中的表达。结果：在55例胶质瘤组织中,p57^kip2蛋白阳性率为38．2％（21／55）,显著低于正常脑组织80．0％（8／10）,P=0．014。p57^kip2蛋白表达在低度恶性（Ⅰ～Ⅱ级）组显著高于高度恶性（Ⅲ～Ⅳ级）纽,P=0．029;生存时间≥2年组显著高于〈2年组,P=0．082。脑胶质瘤组织中p16蛋白表达阳性率为SO．9％（28／SS）,与正常脑组织相比差异无统计学意义,P=0．051。p16蛋白表达在高度恶性（Ⅲ～Ⅳ级）组显著高于低度恶性（Ⅰ～Ⅱ级）组（P=0．022）,生存时间〈2年组显著低于≥2年组,P=0．040。p57^kip2蛋白的表达与p16蛋白的表达存在正相关,rs=0．888,P=0．003。结论：p57^kip2蛋白和p16蛋白在脑胶质瘤中存在异常表达,p57^kip2蛋白和p16蛋白的表达程度与脑胶质瘤的分化程度和预后相关。     

脑胶质瘤组织p14^ARF、p53和p21^WAF1的表达及其意义

目的：探讨p14^ARF、p53和p21^WAF1蛋白在不同级别脑胶质瘤组织中的表达及其在胶质瘤发生、发展中的生物学意义。方法：应用免疫组化SP法检测Ⅱ级和Ⅳ级胶质瘤组织中p14^ARF、p53和p21^WAF1蛋白的表达,并分析其与胶质瘤组织学分级之间的关系。结果：Ⅱ级和Ⅳ级胶质瘤中,p53蛋白的阳性表达率分别为28．00％（7／25）及60．87％（14／23）（P=0．022）,其阳性表达率随胶质瘤恶性程度的增加而升高,Spearman等级相关分析显示,p53的表达与胶质瘤分级呈正相关（P〈0．05）;p21^WAF1的阳性表达率分别为76．00％（19／25）及39．13％（9／23）（P=0．010）,P14^ARF的阳性表达率分别为76．00％（19／25）及34．78％（8／23）（P=0．004）,二者阳性表达率均随胶质瘤恶性程度的增加而降低,Spearman等级相关分析显示,p21^WAF1、p14^ARF的表达与胶质瘤分级呈负相关（P〈0．05）。结论 胶质瘤组织中,p53呈不同程度的过表达,且随胶质瘤恶性程度的增加而表达水平升高;p21^WAF1、p14^ARF随胶质瘤恶性程度的增加表达水平降低。突变型p53蛋白的过表达以及p21^WAF1、p14^ARF蛋白的低表达,可促进胶质瘤的发生、发展。     

胶质瘤DNA倍体、SPF值及EGFR蛋白表达的研究

目的：检测胶质瘤DNA倍性、SPF及EGFR表达，探讨其与胶质瘤病理级别的关系及它们之间相关性。方法：46例手术切除的脑胶质瘤作为实验组；10例正常脑组织作为对照组。采用免疫组化SABC（Strept-Avidin-Bion Complex)法检测EGFR蛋白表达；采用流式细胞技术（Flow-Cytometry,FCM)检测DNA含量及SPF。结果：对照组均为二倍体且无EGFR表达；胶质瘤I级组、Ⅱ级组、Ⅲ－Ⅳ级组DNA异倍体率分别为13．3％、46．2％、77．8％，I级组与Ⅲ－Ⅳ级组、Ⅱ级组与Ⅲ－Ⅳ级组比较差异有显著性（P＜0．05）；EGFR阳性率分别为20．0％、69．2％和83．3％，I级组与Ⅱ级组、I级组与Ⅲ－Ⅳ级组比较差异有显著性（P＜0．05）；SPF值随胶质瘤级别增高而升高，各组比较差异有显著性（P＜0．05）；EGFR阳性胶质瘤DNA发生率及SPF值均明显高于EGFR阴性胶质瘤（P＜0．05）。结论：DNA异倍体的发生、SPF值、EGFR阳性率与胶质瘤恶性级别正相关。EGFR表达与DNA异倍体及SPF有相关性。     

胆管癌组织中TGF-β1、TβRⅡ及p27kip1蛋白的表达及其意义

目的探讨胆管癌组织中TGF—β1、TβRⅡ及p27^kip1表达的相互关系及它们在胆管癌发生发展中的作用。方法应用免疫组织化学S-P法检测49例肝外胆管癌及8例正常胆，营，管组织中TGF—β1、TβRⅡ、p27^kip1的表达，分析其与临床病理学特征的相关性。结果49例胆管癌组织TGF—p1、TβRⅡ和p27^kip1阳性表达率分别为71．43％（35／49）、36．73％（18／49）和40．82％（20／49），而在正常胆管组织分别为12．50％（1／8）、100．00％（8／8）和87．50％（7／8）；TGF-β1、p27^kip1蛋白表达与胆管癌临床分期及转移相关，Ⅲ～Ⅳ期胆管癌的TβRⅡ阳性表达率（25，81%）明显低于Ⅰ～Ⅱ期（55．56％），P〈0，05；TGF—β1及其Ⅱ型受体的共同表达与胆管癌临床分期相关（P〈0．05）；TβRⅡ与；p27^kip1在胆管痛中的表达呈正相关（γs=0．724，P〈0．01）；p27^kip1表达与TGF—β1及TBRⅡ共同表达相关（P〈0，01）。结论TGF-β1表达增高伴TβRⅡ、p27^kip1表达降低提示胆管癌生物学行为不良；胆管癌中p27^kip1蛋白的调控可能与TGF-β1信号转导有关。     

乳腺癌组织p27^kip1的表达及其与细胞增殖的关系

目的：研究乳腺癌组织中细胞周期抑制剂 p27^kip1的表达及其意义,并探讨其与细胞增殖的关系。方法：应用免疫组化SP法检测80例乳腺癌和20例癌旁正常组织中 p27^kip1和增殖细胞核抗原（proliferative cell nuclear antigen,PCNA）的表达。结果：乳腺癌组织中 p27^kip1高表达率为53．75％（43／80）,明显低于癌旁正常组织（P〈0．01）。 p27^kip1表达与组织学分级、TNM分期及淋巴结转移均相关,P〈0．05。乳腺癌组织中 p27^kip1的表达与PCNALI呈负相关,r=0．372,P〈0．05。 p27^kip1高表达的乳腺癌术后5年无病生存率（DFS）明显高于 p27^kip1低表达者（P〈0．05）。结论： p27^kip1表达缺失可促进肿瘤细胞增殖,是判断乳腺癌发生、发展及预后的有效生物学指标。     

人乳头瘤病毒感染对宫颈腺癌中p27^kip1蛋白表达的影响

目的探讨人乳头瘤病毒（HPV）感染对宫颈腺癌中细胞周期调控因子p27^kip1蛋白表达的影响以及二者在宫颈腺癌发生过程的作用。方法采用原位杂交和免疫组化（二步法）检测24例慢性宫颈炎和86例宫颈腺癌组织的HPV16／18DNA和p27^kip1蛋白表达情况。结果HPV16/18DNA在宫颈腺癌组织中的阳性率为65．1％，显著高于慢性宫颈炎组织8．3％（P〈0．01）。p27^kip1蛋白表达在宫颈腺癌组织中的阳性率为55．8％，明显低于慢性宫颈炎组织79.2％（P〈0．05）．HPV16／18感染与宫颈腺癌的组织学类型无关，但与p27^kip1表达呈负相关（P〈0．05）。p27^kip1表达与官颈腺癌组织学类型有明显相关性，透明细胞腺癌p27^kip1阳性表达率明显低于其它类型宫颈腺癌（P〈0．05）。结论HPV16／18感染可能引起p27^kip1蛋白表达异常，从而导致宫颈腺癌发生。     

应用组织微阵列技术研究细胞周期调控因子p27^kip1和p16^Ink4a在宫颈腺癌中的表达

目的 研究细胞周期调控因子p27^kip1、p16^Ink4a在宫颈腺中的表达及临床意义。方法 应用组织微阵列技术结合免疫组化（二步法）检测106例宫颈腺癌组织和22例慢性宫颈炎组织中p27^kip1和p16^Ink4a的表达。结果 宫颈腺癌组织中p27^kip1蛋白阳性表达率为58．5％，明显低于慢性宫颈炎组织（P〈0．05），p16^Ink4a在宫颈腺癌组织中的阳性表达率为70．8％，明显高于慢性宫颈炎组织（P〈0．01）；p16^Ink4a蛋白表达与宫颈腺癌病理分级和组织学类型无明显相关性；p27^kip1蛋白表达与官颈腺癌病理分级无明显相关性，而与组织学类型相关，透明细胞腺癌p27^kip1阳性表达率明显低于其它类型宫颈腺癌（P〈0．05）。结论 p27^kip1和p16^Ink4a在宫颈腺癌的癌变发生过程中起重要作用，二者可能作为宫颈腺癌恶性化的参考指标。     

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.