淋巴结阴性乳腺癌p21waf1、c-erbB-2和p53蛋白表达及其临床意义

目的：探讨腋淋巴结阴性乳腺癌组织中p21^waf1、c-erbB-2和p53基因蛋白表达及其与临床病理参数和预后的关系。方法：应用免疫组化LSAB方法检测121例腋淋巴结阴性乳腺部石蜡切片中p21^waf1、c-erbB-2和p53蛋白的表达情况;同时应用Kaplan-Meier法及多变量Cox比例风险模型,分析3种蛋白表达与预后的关系。结果：（1）p21^waf1蛋白表达率为48．8％,与病理组织学分级、ER状态有关;p53蛋白表达率为36．4％,c-erbB－2蛋白表达率为26．4％,与组织学分级有关;（2）p21^waf1阳性表达与p53表达呈负相关（P＜0．01）;Cox阳性组患者无瘤生存率高于阴性组（P＜0．05）;c-erbB－2阳性组患者无瘤生存率明显低于阴性组（P＜0．01）;Cox模型分析显示仅有c-erbB－2表达对预后有显著影响。结论：乳腺癌组织p21^waf1、c-erbB-2表达与病理组织学分级有相关性;p^21waf1表达依赖于p53途径刺激;p^21waf1、c-erbB－2表达与腋淋巴结阴性乳腺癌预后有关,且c-erbB-2表达是一个独立的预后指标。     

p53在宫颈鳞癌组织中的表达及其意义

目的 通过检测宫颈鳞癌组织p53功能表达状况，观察p53功能表达对宫颈鳞癌预后的影响，以指导治疗。方法 采用western印迹法检测60例宫颈鳞癌组织中p53功能表达。60例宫颈癌患者中位年龄44岁；FIGO分期：Ⅰa期3例，Ⅰb期31例，Ⅱa期10例，Ⅱb期16例。用SPSS10．0统计软件包分析不同的p53功能表达对宫颈鳞癌生物学行为的影响及预后的差异。结果 p53功能表达异常之宫颈鳞癌（16例），其病理分级以Ⅲ级为主（P〈0．01），深肌层浸润及淋巴结转移较p53功能表达正常者（44例）常见（P〈0．01），有50．0％（8／16）的病例在1年内复发（P〈0．01），3年生存率（42．6％）较p53功能表达正常者（78、3％）为低（P〈0、01），平均生存时间（32，93个月）较p53功能表达正常者（60．69个月）明显为短（P〈0．01）。结论 p53功能表达异常者，癌的恶性程度及复发率高，患者的生存期短。     

血管内皮生长因子-C和环氧合酶-2表达与口腔鳞癌淋巴结转移的关系

目的研究环氧合酶-2（COX-2）和血管内皮生长因子-C（VEGF-C）在口腔鳞状细胞癌（OSCC）中的表达及相关性，探讨其与肿瘤淋巴转移的关系。方法采用免疫组化S—P法检测60例OSCC、23例癌前病变、19例良性病变中COX-2、VEGF—C，结合临床病理因素进行分析。结果OSCC中VEGF—C和COX-2表达明显高于口腔癌前病变和良性病变（P〈0．05）。OSCC中VEGF—C蛋白表达与淋巴结转移有明显关系（P〈0．01）；COX-2表达与淋巴结转移、临床分期明显相关（P〈0．05），而与患者年龄、性别、部位、组织学分级无关。VEGF—C和COX-2的表达呈正相关（r=0．519，P〈0．01）。结论COX-2可能参与VEGF-C淋巴管生成通路，在OSCC淋巴结转移中发挥重要作用。     

血管内皮生长因子与膜型基质金属蛋白酶-1在口腔鳞状细胞癌表达及意义

[目的]检测血管内皮生长因子（VEGF）和膜型基质金属蛋白酶-1（MT1-MMP）在口腔鳞状细胞癌（OSCC）中的表达,并探讨其意义。[方法]采用免疫组织化学SP法检测VEGF、MT1-MMP在40例OSCC和10例口腔正常黏膜组织中的表达。[结果]VEGF和MT1-MMP在OSCC组织中的阳性表达率分别为67．50％和75．00％,在正常口腔黏膜组织中均阴性表达．差异有显著性（P〈0．001）。VEGF表达与OSCC的临床分期（P〈0．05）及淋巴结转移显著相关（P〈0．011,与肿瘤的分化程度无关。MT1-MMP表达与OSCC的分化程度（P〈0．05）及淋巴结转移显著相关（P〈0．01）,但与肿瘤的临床分期无相关性。VEGF与MT1-MMP表达呈正相关（rs=0．650,P〈0．001）。[结论]VEGF与MT1-MMP在OSCC发生发展中起重要作用,共同促进OSCC的浸润转移。     

p33ING1、p53在结直肠癌中的表达及其相互关系

目的：探讨p33^ING1、p53在结直肠癌中的表达及其相互关系。方法：应用免疫组化SP法检测60例结直肠癌组织及相应正常黏膜组织中p33^ING1、p53的表达。结果：结直肠癌组织、相应正常黏膜组织中p33^ING1蛋白的阳性表达率分别为43．3％（26／60）、100％（60／60）（P〈O．01），p53蛋白分别为51．6％（31／60）、0％（0／60）。p33^ING1在无淋巴结转移组及淋巴结转移组癌组织中的阳性表达率分别为57．6％（19／33）、25．9％（7／27）（P〈0．05）；在DukesA、B期、Dukes C、D期病例中分别为56．7％（17／30）、30．0％（9／30）（P〈0．05）。在p53表达阴性的29例中有12例（41．4％，12／29）p33^ING1表达缺失，而p53阳性的31例病例中有22例（71．0％，22／31）p33^ING1表达阴性（P〈0．05），在p53蛋白表达阳性的病例中p33^ING1蛋白表达明显缺失，两者表达呈负相关。结论：p33^ING1在结直肠癌组织中低表达，与p53互相协同，在结直肠癌的发生、发展中可能起重要作用。     

食管癌p53、p16、PCNA蛋白表达的临床意义

[目的]探讨p53、p16、PCNA蛋白在食管癌中的表达及临床价值。[方法] 用免疫组织化学染色SP法对50例食管癌标本进行p53、p16、PCNA蛋白测定。[结果] 50例食管癌中，p53、PCNA蛋白阳性表达均为74％（37／50），P16缺失率52％（26／50）。p16缺失与肿瘤浸润深度、淋巴结转移密切相关（P〈0．05、p〈0．01）。而p53、PCNA蛋白同时表达56％（28／50），亦与肿瘤浸润深度、淋巴结转移密切相关（P〈0．05、p〈0．01）。[结论] 食管癌p53、PCNA蛋白同时表达及p16缺失可视为危险预后因素。     

非小细胞肺癌表达p53蛋白与放疗敏感性

目的：研究p53蛋白在非小细胞肺癌（NSCLC）组织中的表达水平与放疗敏感性的关系。方法：采用常规的10％甲醛固定，石蜡包埋标本，包括组化分析p53蛋白的表达及其与放疗敏感性的关系。结果：p53蛋白表达阳性率为40％（20／50），70％（21／30）％的p53蛋白（－）肿瘤放疗有效，而p53蛋白（＋）中仅15％（3／20）有效（P＜0．01）。结论：p53蛋白可作NSCLC放疗敏感性预测的参考指标。     

乳腺癌组织中HPV16 18E6及p53 MCM7蛋白的表达及意义

目的：探讨人乳腺癌及乳腺良性病变中高危型HPV16、18感染和细胞周期复制调控蛋白p53、MCM7异常表达与人乳腺癌发生、发展的关系方法：采用免疫组织化学SP法，检测30例正常乳腺、30例乳腺腺痛，55例乳腺癌、5例导管原位癌及其癌旁组织中HPV16、18E6，p53和MCM7蛋白的表达。结果：55例乳腺癌组织中HPV16、18E6，p53和MCM7蛋白的阳性表达率分别为58．18％、38．18％和96.36％，均显著高于正常组和腺病组（P〈0．01、P〈0．001、P〈0．05）浸润性导管癌HPV16、18E6阳性组中p53蛋白的阳性表达率显著低于HPV16、18E6阴性组（P〈0．01）HPV16、18E6与p53蛋白的表达呈负相关（r=-0．5769；P〈0．001），而与MCM7蛋白表达呈正相关（r=0．5442；P〈0．001）MCM7蛋白的阳性表达率与浸润性导管癌组织学分级、淋巴结转移和肿块直径有关（P〈0．01、P〈0．03、P〈0．01）结论：高危型HPV16、18E6感染后p53功能的失活和MCM7蛋白的高表达导致细胞周期复制调控异常，可能涉及了HPV感染后乳腺癌的发生、发展过程MCM7的高表达与乳腺癌细胞的增殖、侵袭和转移有关二者联合检测可作为评价HPV感染后乳腺上皮细胞的增殖状态、早期诊断和预测肿瘤生物学行为的重要指标。     

MMP-2和p53表达在结直肠癌组织中的表达及其临床意义

目的探讨人结直肠癌组织中基质金属蛋白酶-2（MMP-2）和p53表达与其临床病理特征的关系。方法采用免疫组化EliVisionTM plus法,检测40例结直肠癌、20例结直肠腺瘤和20例正常结直肠组织中MMP-2和p53蛋白表达水平。结果40例结直肠癌组织中MMP-2和p53阳性表达率分别为80．0％（32／40）和82．5％（33／40）,明显高于正常结直肠组织、结直肠腺瘤组织中的阳性率（均为0、30．0％）。MMP-2和p53在结直肠癌中的表达与患者年龄、性别、肿瘤大小、肿瘤发生部位均无相关性（P〉0．05）,与组织学分化程度呈负相关,分化程度越差,蛋白阳性表达率越高,有淋巴结转移组蛋白阳性表达率明显高于无淋巴结转移组（P〈0．05）,与TNM分期呈正相关（P〈0．05）。MMP-2表达与肿瘤浸润深度有关（P〈0．05）,有远处转移组MMP-2蛋白阳性表达率明显高于无远处转移组（P〈0．05）,p53表达与肿瘤浸润深度以及远处转移均无相关性（P〉0．05）。结直肠癌组织中MMP-2表达与p53蛋白表达呈正相关（γs’=0．3742,P=0．0069）。结论MMP-2表达与结直肠癌淋巴结侵袭转移有关,p53基因突变后MMP-2表达增强。联合检测MMP-2和p53在结直肠癌中的表达对评估结直肠癌病情有一定意义。     

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。     

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.