大肠腺瘤及癌变组织hMLH1和hMSH2表达与细胞凋亡的研究

目的：探讨hMLH1和hMSH2基因在大肠腺瘤及其癌变中的作用,及其表达对细胞凋亡的影响。方法：采用免疫组织化学染色检测63例大肠腺瘤、20例腺瘤癌变和20例大肠癌组织hMLH1和hMSH2表达;同时采用TUNEL法检测其细胞凋亡指数（AI）。结果：大肠腺瘤、腺瘤癌变和大肠癌组织错配修复基因hMLH1、hMSH2的表达率逐渐降低,与正常大肠相比相差显著,随腺瘤不典型增生程度增加其阳性率逐渐降低;大肠腺瘤、腺瘤癌变和大肠癌中hMLH1表达缺失者细胞凋亡指数较显著高于其阳性者,且大肠腺瘤不典型增生Ⅰ、Ⅱ、Ⅲ级hMLH1-与hMLH1＋组存在差异显著;而hMSH2-与hMSH2-间AI仅大肠腺瘤组有显著性差异,不典型增生Ⅰ、Ⅱ级组hMSH2-与hMSH2＋间AI差异显著,而不典型增生Ⅲ级组hMSH2蛋白的表达阴性与阳性间AI无统计学差异。结论：DNA错配修复基因突变或功能缺失与大肠癌的发生有关,可能系大肠癌发生过程中的早期事件,且可能与大肠肿瘤细胞凋亡活性增加相关。     

hMLH1和hMSH2蛋白表达与散发性大肠癌

目的通过对散发性大肠癌中错配修复基因表达的检测,探讨错配修复基因与大肠癌发生和演进的关系.方法采用蛋白提取技术提取肿瘤组织蛋白,利用免疫印记技术对hMSH2和hMLH1蛋白表达情况进行检测,应用方差分析和t检验对数据进行统计学分析.结果 70岁以上组hMLH1蛋白表达水平显著低于70岁以下两组,在不同分化各组间差异有显著性;右半结肠癌hMHL1蛋白表达显著低于除直肠以外其他部位的肿瘤;无转移肿瘤hMLH1蛋白的表达显著低于有转移肿瘤;其表达与性别无显著相关.hMSH2蛋白表达水平与患者性别、年龄、肿瘤部位、分化程度及转移间均无显著相关.结论高龄所造成的hMLH1基因蛋白表达降低可能是导致散发性大肠癌的相关因素之一;hMLH1基因表达降低与右半结肠癌的发生关系密切并影响其分化;hMLH1基因表达较高的肿瘤可能易出现转移.hMSH2基因与大肠癌临床病理间无密切联系.     

大肠癌组织COX-2的表达及其与肿瘤细胞增生和凋亡的关系

目的 探讨大肠癌中环氧化酶-2（c yclooxygenase-2,COX-2）表达及其与癌细胞增生和凋亡的关系.方法 采用免疫组织化学法检测60例大肠癌、20例大肠腺瘤和20例癌旁正常大肠黏膜中COX-2和PCNA的表达,并采用TUNEL法检测原位细胞凋亡水平.结果 大肠癌组织中COX-2阳性表达、PI及AI均显著高于大肠腺瘤及正常大肠黏膜组织（P＜0.05）;COX-2的高表达与大肠癌肿瘤大小、淋巴结转移和临床分期有关,与肿瘤生长部位、分化程度无关.COX-2阳性大肠癌组中PI高于COX-2阴性大肠癌组,AI低于COX-2阴性大肠癌组（P＜0.05）.结论 COX-2的过度表达可促进大肠癌细胞增生、抑制细胞凋亡,在大肠癌的发生、发展过程中起着重要的作用.     

错配修复基因hMLH1和hMSH2的表达与人卵巢癌顺铂耐药的关系

目的:探讨DNA错配修复基因hMLH1和hMSH2的表达在人卵巢癌细胞顺铂耐药现象中的作用.方法:MTT法检测卵巢癌细胞对顺铂的敏感性,Hoechst免疫荧光染色检测顺铂作用下敏感及耐药细胞的凋亡情况,并使用RT-PCR技术及West-ern blotting技术分别检测顺铂敏感性人卵巢癌细胞及耐药顺铂人卵巢癌细胞中错配修复基因hMLH1及hMSH2的转录与翻译表达变化.结果:同一顺铂浓度作用下,耐药顺铂人卵巢癌细胞的凋亡率明显低于顺铂敏感性人卵巢癌细胞,且后者的错配修复基因hMLH1和hMSH2的mRNA及蛋白表达水平均显著高于前者.结论:顺铂可诱导卵巢癌细胞凋亡.在耐药顺铂人卵巢癌细胞中,错配修复基因hMLH1和hMSH2低表达可能是导致顺铂耐药发生的重要原因.     

PCNA,P53在大肠腺癌,腺癌中的表达及相关性研究

采用免疫组织化学方法，对１５０例大肠腺瘤、腺癌进行ＰＣＮＡ及Ｐ５３癌基因蛋白检测，并用１４例正常大肠粘膜对照。结果显示；ＰＣＮＡ的表达，在腺瘤不典型增生１级组，腺癌不典型增生Ⅱ、Ⅲ组组、腺瘤癌变组及腺癌高、中、低分化各 中明显呈递增趋势。Ｐ５３癌基因蛋白在畜产品组中表达最高。两者之间的相关性无统计学意义，但在腺瘤不典型增生Ⅱ、Ⅲ级及腺瘤癌变组中，两者的表达具有显著性差异。提示ＰＣＮＡ及Ｐ５３癌基因     

错配修复基因的异常表达与淮安食管癌发病的关系

背景与目的： 研究错配修复相关基因hMLH1和hMSH2的mRNA表达水平与食管癌发病的关系。 材料与方法： 收集112例淮安地区食管癌新发病例的食管癌组织及远端癌旁组织,采用实时荧光定量PCR方法定量分析食管癌组织与癌旁组织中hMLH1和hMSH2基因的表达水平,应用t检验和logistic回归分析评价基因的表达水平与食管癌的关系。 结果： hMSH1基因的mRNA表达水平在食管癌与癌旁组织间的差异不明显,而hMSH2基因的mRNA表达水平在食管癌组织显著低于癌旁组织(下调了51.2％),条件logistic回归分析表明hMSH2的表达下调与食管组织癌变有统计学关联(OR=1.311,95％CI：1.075~1.599)。 结论： 错配修复相关基因hMSH2的表达水平下降提示食管癌组织错配修复能力异常,可能是淮安地区食管癌发病的危险因素之一。     

X线照射对鼻咽癌细胞hMSH2和hMLH1表达的影响

目的研究X线照射对鼻咽癌细胞中错配修复基因hMSH2和hMLH1表达的影响,探讨放射损伤后肿瘤细胞的DNA错配修复机制。方法将鼻咽癌CNE-1细胞分为实验组和对照组,对2组细胞进行X线分次外照射。实验组每次照射剂量为2Gy,总剂量为10Gy。对照组每次照射剂量为0Gy。应用RT-PCR、免疫细胞化学及Western blot方法,检测照射终止后不同时间点细胞hMSH2和hMLH1的表达。结果实验组细胞在照射后hMSH2mRNA和蛋白的表达均显著强于对照组(P<0.01);hMLH1mRNA及蛋白表达与对照组比较无显著差异(P>0.05)。结论放射可以诱导鼻咽癌细胞hMSH2表达;hMSH2对放射造成的DNA损伤可能有修复作用,这可能是临床上鼻咽癌放疗敏感性降低的原因之一。     

散发性大肠癌的错配修复缺陷研究

目的探讨错配修复缺陷的散发性大肠癌的临床病理特征及错配修复缺陷检测手段的应用。方法对71例散发性大肠癌行hMLH1启动子甲基化检测、微卫星不稳定检测以及hMLH1和hMSH2的免疫组化检测,分析错配修复缺陷的散发性大肠癌的临床病理特征,探讨三种检测方法的应用价值。结果hMLH1基因启动子甲基化、微卫星不稳定和错配修复蛋白表达的阳性率分别为9.9%,9.9%和71.0%,三者密切相关。hMLH1启动子甲基化和微卫星不稳定的散发性大肠癌均具有结肠癌多发和低分化腺癌相对多见的特征。错配修复蛋白表达阴性的散发性大肠癌仅具有低分化腺癌相对多见的特征。结论错配修复缺陷的散发性大肠癌具有结肠癌和低分化腺癌多发的倾向,hMLH1启动子甲基化和微卫星不稳定以及错配修复蛋白的失表达三者密切相关。     

PCNA、p53在大肠腺瘤、腺癌中的表达及相关性研究

采用免疫组织化学方法，对150例大肠腺癌、腺癌进行PCNA及P53癌基因蛋白检测，并用14例正常大肠粘膜作对照。结果显示：PCNA的表达，在腺癌不典型增生Ⅰ级组、腺癌不典型增生Ⅱ、Ⅲ级组、腺癌癌变组及腺癌高、中、低分化各组中明显呈递增趋势。p53癌基因蛋白则在腺癌癌变组中表达最高。两者之间的相关性无统计学意义，但在腺瘤术典型增生Ⅱ、Ⅲ级组及腺癌癌变组中，两者的表达均具有显著性差异。提示PCNA及p53癌基因蛋白的检测，对大肠腺癌癌变的诊断具有重要意义。     

c-met基因表达与大肠腺瘤演化与癌变过程相关性的研究

目的:评价大肠腺瘤演化与恶变过程中c-met基因的表达及其临床意义。方法:利用组织微阵列技术检测41例不同阶段的不典型增生的大肠腺瘤、16例早期癌变的大肠腺瘤和56例进展期大肠癌标本中的c-met基因。结果:在大肠腺瘤非不典型增生、轻度不典型增生、中重度不典型增生、早期癌变和进展期癌的演变中,c-met基因的阳性率分别为43.75%、50.0%、66.7%、75.0%和82.1%;过表达率分别为18.8%、10.0%、46.7%、50.0%和66.1%。而且进展期癌c-met基因的阳性率和过表达率均显著高于大肠腺瘤非不典型增生,P<0.01。大肠腺瘤演变程度与c-met阳性表达强度之间的密切关系分析显示,两者显著相关,P=0.011。结论:c-met基因表达与大肠腺瘤演化的程度及恶变相关;大肠腺瘤不典型增生级别越高,c-met基因表达越强。大肠腺瘤早期癌变时c-met基因已呈过表达状态。     

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.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.     

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.     

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.