人乳头状瘤病毒16，18型感染及MCM蛋白表达调控与人乳腺癌

高危型人乳头状瘤病毒16、18型E6、E7蛋白导致p53、Rb抑癌基因功能的失活以及E6、E7可分别直接或间接调控细胞周期DNA复制起始调节准许因子一微小染色体维持蛋白7的异常表达从而导致细胞周期复制异常涉及了HPV16型和HPV18型感染后人乳腺癌的发生、发展过程，本文就其相关机制及临床意义作一综述。     

乳腺浸润性导管癌组织中HPV16、18E6及MCM7蛋白的表达

目的:检测人乳腺浸润性导管癌及乳腺良性病变中HPV16、18E6和MCM7蛋白的表达,探讨高危型HPV感染和细胞周期复制调控异常与人乳腺癌发生、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例乳腺腺病,52例乳腺浸润性导管癌组织中HPV16、18E6和MCM7蛋白的表达.结果:癌组中HPV16、18E6和MCM7蛋白的阳性表达分别为57.69%和96.15%,均显著高于正常组和腺病组(P＜0.02、P＜0.05).HPV16、18E6与MCM7蛋白阳性表达呈正相关(r=0.5442;P＜0.001).MCM7蛋白阳性表达与IDC组织学分级、淋巴结转移和肿块大小有关(P＜0.01、P＜0.03、P＜0.01).结论:高危型HPV16、18感染和MCM7蛋白的高表达导致细胞周期复制调控异常涉及了HPV感染后乳腺癌的发生发展过程.MCM7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感染乳腺上皮细胞的增殖状态和评价临床预后的生物学指标.     

乳腺浸润性导管癌组织中HPV16、18E6及MCM7蛋白的表达

目的：检测人乳腺浸润性导管癌及乳腺良性病变中HPV16、18E6和MCM7蛋白的表达,探讨高危型HPV感染和细胞周期复制调控异常与人乳腺癌发生、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例乳腺腺病,52例乳腺浸润性导管癌组织中HPV16、18E6和MCM7蛋白的表达。结果：癌组中HPV16、18E6和MCM7蛋白的阳性表达分别为57．69％和96．15％,均显著高于正常组和腺病组（P〈0．02、P〈0．05）。HPV16、18E6与MCM7蛋白阳性表达呈正相关（r=0．5442;P〈0．001）。MCM7蛋白阳性表达与IDC组织学分级、淋巴结转移和肿块大小有关（P〈0．01、P〈0．03、P〈0．01）。结论：高危型HPV16、18感染和MCM7蛋白的高表达导致细胞周期复制调控异常涉及了HPV感染后乳腺癌的发生发展过程。MCM7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感染乳腺上皮细胞的增殖状态和评价临床预后的生物学指标。     

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例乳腺腺病,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。     

细胞周期调控异常与宫颈癌

细胞周期调控异常，尤其是G1-S期调控异常在肿瘤的发生中起重要作用，G1-S期调控主要包括Rb通路（p16^INK4A-CyclinD1-CDK4／6-pRb-E2F）和p53通路（p14^ARF-Mdm2-p53）。HPV感染已被确认为是宫颈癌发生的首要病因，尤其是高危型HPV16、18癌蛋白E6、E7可分别与肿瘤抑制蛋白p53和pRb结合，使p53通路和Rb通路失活，细胞周期调控异常，导致宫颈癌的发生。     

细胞周期调控异常与宫颈癌

细胞周期调控异常,尤其是G1-S期调控异常在肿瘤的发生中起重要作用,G1-S期调控主要包括Rb通路(p161NK4A-CyclinD1-CDK4/6-pRb-E2F)和p53通路(p14ARF-Mdm2-p53).HPV感染已被确认为是宫颈癌发生的首要病因,尤其是高危型HPV16、18癌蛋白E6、E7可分别与肿瘤抑制蛋白p53和pRb结合,使p53通路和Rb通路失活,细胞周期调控异常,导致宫颈癌的发生.     

p16~(INK4A)和HPV16 E7/HPV18 E6在ASCUS中的表达及临床意义

目的:探讨p16 INK4A和HPV16 E7/HPV18 E6在宫颈细胞学诊断为非典型性鳞状细胞不明确意义型(ASCUS)中的表达及筛查潜在宫颈病变的价值。方法:对150例ASCUS患者行阴道镜检查并取活检,同时对该150例患者的TCT标本进行免疫细胞化学染色检测p16INK4A的表达和RT-PCR法检测其中HPV16型E7蛋白和18型E6蛋白(HPV16 E7/HPV18 E6)mRNA的表达。结果:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中表达的阳性率分别为37.33%和46.67%,随着病理级别的增加,p16INK4A和HPV16E7/HPV18 E6 mRNA表达的阳性率也随之增加;p16INK4A和HPV16 E7/HPV18 E6 mRNA筛查ASCUS中宫颈病变的灵敏度、特异度、阳性预测值和阴性预测值分别为0.88、0.95、0.91、0.93和0.81、0.75、0.67、0.86,在p16INK4A和HPV16 E7/HPV18 E6 mRNA阳性的样本中,宫颈病变发生率分别为91.07%和67.14%,均明显高于阴性样本中的发病率7.45%和13.75%(P<0.001);ASCUS中宫颈病变样本中p16INK4A和HPV16 E7/HPV18 E6 mRNA呈高表达,且具有较高的一致性(κ=0.6475)。结论:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中病理诊断为宫颈病变的样本中均呈高表达,对筛查潜在的宫颈病变具有重要意义,其中p16INK4A的筛查效能优于HPV16E7/HPV18E6mRNA;p16INK4A能间接反映HPV的转录活性,在ASCUS的分流中有重要意义,且可视性的p16INK4A免疫染色比HPV检测更直观。     

真核细胞内外源性HPV16 E7癌基因表达及其对cdc25A及Cyclin E表达的影响

背景与目的:人乳头状瘤病毒(HPV)感染及其引发的抑癌基因功能丧失和细胞周期调控失调是宫颈癌发病的重要因素。HPV16诱发宫颈癌的机制主要与其两个早期开放读码框架E6、E7转化基因密切相关。HPVE6、E7引起细胞生长和增殖异常,同时伴有Cyclin A、Cyclin D1、CDK4等细胞周期蛋白的表达异常。本研究采用体外基因转染技术将HPV16 E7基因转入靶细胞,通过对目的基因瞬时表达的检测,进而观察在E7病毒癌蛋白的影响下调控G1/S检验点的几种细胞周期调节蛋白的表达,以探讨HPV16型E7基因外源性表达对子宫颈癌HeLa细胞细胞周期调节因子cdc25A及细胞周期蛋白E(Cyclin E)的影响。方法:从宫颈癌标本中经PCR扩增回收HPV16 E7基因片段,将其插入腺病毒穿梭质粒pAdTrack-CMV,与腺病毒骨架质粒pAdEasy-1构建重组腺病毒基因组Ad-E7。用脂质体介导Ad-E7导入包装细胞人胚肾细胞系HEK-293细胞,包装出完整腺病毒颗粒。测定病毒上清液滴度,感染体外培养的HeLa细胞。采用RT-PCR方法检测转染前后HeLa细胞cdc25A的mRNA表达的差异;激光扫描共聚焦显微镜(LSCM)检测转染前后Cyclin E表达的差异。结果:荧光显微镜下,转染后HEK-293细胞和HeLa细胞表达绿色荧光蛋白。RT-PCR结果显示转染后,HeLa细胞cdc25A的mRNA含量较转染前显著增加[感染前灰度值0.23±0.10,感染后0.87±0.22(P<0.01)],LSCM检测结果显示转染后Cyclin E表达较转染前明显增加。结论:重组腺病毒可以成功介导外源性HPV16 E7基因在HeLa细胞内表达,HPV16 E7基因促进HeLa细胞周期调节因子cdc25A和Cyclin E的表达。     

KAI1蛋白与人乳头状瘤病毒E6、E7蛋白在子宫颈癌组织中的表达及其意义

目的 探讨高危型人乳头状瘤病毒（HPV）感染和肿瘤转移抑制蛋白KAIl在子宫颈癌形成及进展中的意义.方法 对117例石蜡包埋子宫颈组织[正常对照20例、子宫颈上皮内瘤样病变（CIN）58例、子宫颈癌39例]采用免疫组织化学SP法检测KAI1蛋白、HPV16/18E6、HPV16E7蛋白的表达情况.结果 在正常子宫颈组织、CIN和子宫颈癌组织中,KAII阳性表达率分别为90.0％（18/20）、72.4％（42/58）、25.6％（10/39）,呈下降趋势,差异有统计学意义（P＜0.01）. HPVI6/18E6阳性表达率分别为0（0/20）、31.0％（18/58）、41.0％（16/39）,差异有统计学意义（P＜ 0.01）;HPV16E7阳性表达率分别为0（0/20）、34.5％（20/58）、64.1％（25/39）,差异有统计学意义（P＜0.01）.但KAI1与HPV16/18E6、HPV16E7阳性表达间无相关性（P=0.429）.KAI1蛋白在子宫颈癌中的阳性表达率与细胞分化程度、临床分期、淋巴结转移有关（均P＜ 0.05）,与发病年龄无关（P＞0.05）;HPV感染与子宫颈癌发病年龄、临床分期、细胞分化程度、淋巴结转移均无关（均P＞ 0.05）.结论 KAI1蛋白在子宫颈癌中的表达下调,HPV16/18E6、HPV16E7感染与KAI1蛋白表达无关.     

p16INK4A和HPV16 E7/HPV18 E6在ASCUS中的表达及临床意义

目的：探讨p16^INK4A和HPV16 E7／HPV18 E6在宫颈细胞学诊断为非典型性鳞状细胞不明确意义型（ASCUS）中的表达及筛查潜在宫颈病变的价值。方法：对150例ASCUS患者行阴道镜检查并取活检,同时对该150例患者的TCT标本进行免疫细胞化学染色检测p16^INK4A的表达和RT-PCR法检测其中HPV16型口蛋白和18型E6蛋白（HPV16 E7／HPV18 E6）mRNA的表达。结果：p16^INK4A和HPV16 E7／HPV18 E6 mRNA在ASCUS中表达的阳性率分别为37．33％和46．67％,随着病理级别的增加,p16^INK4A和HPV16 E7／HPV18 E6 mRNA表达的阳性率也随之增加;p16^INK4A和HPV16 E7／HPV18 E6 mRNA筛查ASCUS中宫颈病变的灵敏度、特异度、阳性预测值和阴性预测值分别为0．88、0．95、0．91、0．93和0．81、0．75、0．67、0．86,在p16^INK4A和HPV16 E7／HPV18 E6 mRNA阳性的样本中,宫颈病变发生率分别为91．07％和67．14％,均明显高于阴性样本中的发病率7．45％和13．75％（P〈0．001）;ASCUS中宫颈病变样本中p16^INK4A和HPV16 E7／HPV18 E6 mRNA呈高表达,且具有较高的一致性（K=0．6475）。结论：p16^INK4A和HPV16 E7／HPV18 E6 mRNA在ASCUS中病理诊断为宫颈病变的样本中均呈高表达,对筛查潜在的宫颈病变具有重要意义,其中p16^INK4A的筛查效能优于HPV16 E7／HPV18 E6 mRNA;p16^INK4A能间接反映HPV的转录活性,在ASCUS的分流中有重要意义,且可视性的p16^INK4A免疫染色比HPV检测更直观。     

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.