Ki-67、端粒酶在结直肠良、恶性病变中的表达及其意义

目的　探讨Ki 67、端粒酶在正常结直肠粘膜、结直肠良、恶性病变中的表达及其临床意义。方法　流式细胞仪测定 41例结直肠癌、9例结直肠良性病变和 1 3例正常结直肠粘膜标本的Ki 67标记指数 ,半定量端粒重复扩增 (TRAP) 银染法测定其端粒酶活性 ,并行统计学处理。结果　正常结直肠粘膜、良、恶性病变的Ki 67标记指数与端粒酶相对值的组间比较均有显著性差异 (P <0 .0 5) ;结直肠癌病人的两指标在各临床资料的组间比较中均无显著性差异 (P >0 .0 5) ;两者联合检测鉴别结直肠良、恶性病变的灵敏度、特异性分别为 80 .49%、77.78% ;结直肠癌病人两指标线性相关系数为 0 .852 (P <0 .0 5)。结论　Ki 67表达、端粒酶活性是鉴别正常结直肠粘膜、结直肠良、恶性病变有价值的两项指标 ,但端粒酶活性鉴别结直肠良、恶性病变的灵敏度不理想 ;两指标与结直肠癌的一些临床指标无关 ;结直肠癌病人的两指标间存在线性相关关系。     

Ki-67和cyclin D1蛋白表达的检测对胃肠道间质瘤良恶性判断的意义

目的　探讨Ki -67和cyclinD 1蛋白表达的检测对胃肠道间质瘤(GISTs)良恶性判断的意义。方法　应用免疫组织化学EnVision二步法检测41例GISTs组织中Ki -67和cyclinD1蛋白表达情况。结果　41例GISTs分为良性组(6例)、交界组(13例)和恶性组(2 2例) ,良性组、交界组与恶性组GISTs的Ki- 67标记指数分别为(8.5±3 .9) %、(16.8±8.6) %和(2 1.8%±8.3 ) % ,3组Ki 67标记指数比较有非常显著性差异(P <0 .0 1) ;Ki- 67标记指数与核分裂像数目、肿瘤直径及肿瘤坏死有关。良性组、交界组与恶性组GISTs的cyclinD1阳性表达率分别为16.7% (1/6)、5 3 .8% (7/13 )和68.2 % (15 /2 2 ) ,3个组cyclinD 1阳性表达率比较有显著性差异(P <0 .0 5 ) ,且良性组与交界组以及良性组与恶性组间cyclinD1阳性表达率有显著性差异(P <0 .0 5 ) ,但交界组和恶性组cyclinD1阳性表达率比较无显著性差异(P >0 .0 5 ) ;cyclinD 1阳性表达率与核分裂象数目有关,而与肿瘤直径及肿瘤坏死无关。结论　Ki- 67和cyclinD1蛋白是胃肠道间质瘤良恶性判断的有价值参考指标,结合胃肠道间质瘤形态学综合分析,更能准确客观地判断胃肠道间质瘤的良恶性。     

大肠癌中MAGE-A1的表达及其与肿瘤细胞增殖的关系

目的 研究大肠癌中肿瘤特异性抗原MAGE-A1,Ki-67的表达及其相关性,探讨他们与大肠癌生物学行为的关系及其作为免疫治疗靶点的可行性. 方法 免疫组化S-P法,利用鼠抗人MAGE-A1、Ki-67单克隆抗体检测60例大肠癌标本中MAGE-A1,Ki-67表达水平.结果 60例大肠癌中MAGE-A1表达率为33.3%(20/60),高表达率为5%(3/60),低表达率为28.3%(17/60),正常组织表达率为3.33%,大肠癌和正常组织之间的表达具有显著性差异(P<0.05).Ki-67表达率为53.3%(32/60),高表达率为33.3%(20/60),低表达率为20%(12/60),正常组织表达率为16.6%(4/30),大肠癌和正常组织之间的表达具有显著性差异(P<0.05).MAGE-A1与分化程度、淋巴结转移有关(P<0.05),Ki-67与分化程度有关(P<0.05).MAGE-A1阳性表达的高低与Ki-67阳性表达的高低相关(r=0.384,P<0.05).结论 MAGE-A1在大肠癌中有较高的表达,并且与细胞增殖相关,正常组织不表达,MAGE-A1阳性患者的预后好,有望作为免疫治疗的靶点.     

流式细胞术Ki67/DNA双标记法在实体肿瘤中的应用

目的 探讨流式细胞术双标记法检测恶性实体肿瘤细胞DNA含量、细胞周期和Ki67表达和组织学分级之间的关系.方法 利用流式细胞术Ki67/DNA双标记法同时检测87例新鲜恶性实体肿瘤的DNA含量、细胞周期和增殖核抗原Ki67的表达.结果 异倍体发生率为40.2%,其中高分化肿瘤为11.1%,中分化肿瘤为37.5%,低分化肿瘤为46.3%.Ki67阳性细胞为0.5%～87%(17.36%±16.6%).S期细胞百分比为0～24%(5.28%±4.85%).高分化肿瘤S期细胞百分比及增殖核抗原Ki67的表达明显低于中分化和低分化肿瘤.统计学上有显著性差异(P＜0.01).中分化和低分化肿瘤之间则差异无显著性(P＞0.05).异倍体肿瘤S期细胞百分比高于二倍体肿瘤,差异有显著性(P＜0.01),而Ki67的表达在两者之间无显著性差异.结论 流式细胞术Ki67/DNA双标记法可同时检测实体恶性肿瘤细胞的DNA含量、细胞周期和增殖核抗原Ki67的表达,并能进一步阐明这些参数与组织学分级的关系.方法 简便、快速,有利于对肿瘤生物学特性的了解.     

APC、β-catenin、C-myc和Cyclin D1在大肠癌组织中的表达及其意义

背景与目的:Wnt信号转导通路成员各癌基因、抑癌基因的异常,激活下游相关靶基因的转录,在肿瘤发生发展中起重要作用.本研究通过检测不同大肠组织中APC、β-catenin、C-myc和Cyclin D1的表达情况,探讨其在大肠癌发生中的意义.方法:应用免疫组织化学方法检测30例正常大肠粘膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC、β-catenin、C-myc和Cyclin D1蛋白的表达情况.以β-catenin在细胞膜表达为正常表达,而在胞浆和/或胞核表达为异位表达.结果:大肠癌和大肠腺瘤恶变组织APC阳性率分别为44.0%和40.0%,显著低于大肠腺瘤(86.7%)和正常大肠粘膜(100%)(P＜0.01).大肠癌、大肠腺瘤恶变组织和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为62.0%、50.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤(P＜0.01).大肠癌、大肠腺瘤恶变组织、大肠腺瘤中C-myc表达率分别为56.0%、60.0%、46.7%,均显著高于正常大肠粘膜(0%)(P＜0.01),而Cyclin D1阳性率分别为66.0%、60.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01).大肠癌Cyclin D1表达率显著高于大肠腺瘤(P＜0.01).大肠癌中β-catenin异位表达与C-myc和Cyclin D1表达呈正相关关系(r=0.63,P＜0.01;r=0.57,P＜0.01),而与APC表达呈负相关关系(r=-0.39,P＜0.05).结论:大肠癌组织中存在APC低表达和/或β-catenin异位表达,以及C-myc和Cyclin D1的过度表达,4种基因蛋白可能在大肠癌发生过程中起重要作用.     

PCNA和EGFR在不同性质大肠肿瘤中表达的研究

目的探讨PCNA和EGFR在不同性质大肠肿瘤中的表达及意义。方法采取正常大肠粘膜10例,大肠腺瘤20例,大肠癌粘膜30例。应用免疫组化染色方法（SP法）,在连续切片上同步检测PCNA和EGFR的表达。结果PCNA染色阳性物质主要定位于细胞核,EGFR染色阳性物质主要定位于细胞膜。PCNA和EGFR阳性细胞在大肠腺瘤和大肠癌中的分布呈不同程度的异质性。正常大肠粘膜、大肠腺瘤和大肠癌粘膜PCNA阳性细胞数分别为2．42±1．02、10．17±4．96和20．21±6．58,各组间比较均有极显著性差异（P＜0．01）;EGFR阳性率分别为0、30％和73．33％．各组间比较也有显著性差异（P＜0．05）。PCNA和EGFR的表达与大肠癌的分化程度、分期和淋巴结转移有关,与组织学类型无关。30例大肠癌粘膜PCNA和EGFR的表达里显著性正相关（P＜0．05）;60例不同性质大肠粘膜PCNA和EGFR的表达里极显著性正相关关系（P＜0．01）。结论PCNA和EGFR都是反映细胞增殖活性的重要指标。结合病理形态学观察,同时检测PCNA和EGFR的表达,能更客观更准确地判断大肠癌的恶性程度和生物学特性。     

早期大肠癌中环氧化酶-2的表达及其临床意义

目的　研究早期大肠癌中COX 2的表达及其临床意义。方法　使用免疫组化染色法分别检测了 32例早期大肠癌外科术后石蜡标本、33例大肠腺瘤、18例正常大肠粘膜活检组织中COX 1和COX 2蛋白的表达。结果　依表达程度由 ( )至 (+++)四级计算 ,COX 2的表达率在正常结肠粘膜中分别为 83.3%、16 .7%、0 %、0 % ;在结肠腺瘤中分别为 12 .1%、4 2 .4 %、36 .4 %、9.1% ;早期大肠癌中分别为 6 .3%、2 8.1%、4 6 .9%、18.7%。早期大肠癌、大肠腺瘤中COX 2的表达率均明显高于正常粘膜 (P <0 .0 1) ,但早期大肠癌与大肠腺瘤中COX 2的表达率无显著性差异。COX 2的表达与早期大肠癌、大肠腺瘤各项被研究的临床病理特征无关。COX 1在早期大肠癌 ,大肠腺瘤及正常肠粘膜中呈低水平表达。结论　COX 2的表达在由正常大肠粘膜至大肠腺瘤、早期癌的发展过程中呈上调趋势。COX 2的表达是大肠肿瘤形成过程中的早期事件 ,不能作为大肠癌早期诊断的癌标记物。     

大肠癌组织中TGF-β1表达与癌细胞增殖活性的关系

目的:研究大肠癌组织中转化生长因子β1(transforminggrowthfactorβ1,TGFβ1)表达的意义及其与癌细胞增殖活性的关系。方法:运用免疫组化SP法检测70例大肠癌和10例正常大肠黏膜TGFβ1与Ki67抗原的表达。结果:大肠癌TGFβ1表达率(52.9%)与Ki67LI值(38.6±10.2)明显高于正常大肠黏膜(10.0%,12.1±6.5),P值分别为0.011和0.000。淋巴结转移组TGFβ1表达率(65.0%)明显高于无淋巴结转移组(36.7%),P=0.019;Duke’sC期TGFβ1表达率(64.3%)明显高于A期(27.3%)和B期(41.2%),P=0.049。Ki67表达与大肠癌淋巴结转移、Duke’s分期、组织学类型和分化程度均无关,P值分别为0.076、0.723、0.250和0.056。大肠癌TGFβ1阳性表达组Ki67LI值(42.2±9.6)明显高于TGFβ1阴性表达组(36.1±7.3),P=0.004。结论:TGFβ1过表达的大肠癌组织细胞具有较强的增殖活性,TGFβ1不能抑制癌细胞增殖。TGFβ1促进大肠癌细胞浸润和转移。TGFβ1过表达可作为评估大肠癌生物学行为的参考指标。     

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.