周期蛋白B1和D1在重度反流性食管炎、Barrett食管和食管腺癌中的表达及相关性研究

 目的　探讨周期蛋白（Cyclin）B1及D1在Barrett食管、Barrett食管合并不典型增生（DY）和食管腺癌中表达的临床意义。方法　应用免疫组织化学SP法测定68例患者食管组织标本Cyclin B1和Cyclin D1,其中重度反流性食管炎（RE）25例,Barrett食管（BE）35例,其中8例DY,8例食管腺癌（EA）,另取10例正常食管黏膜组织作为对照。结果　Cyclin B1 和Cyclin D1在 BE、DY、EA组检测样本中均有高表达,而在正常对照组及RE组黏膜组织中仅有少量表达,差异有统计学意义（P＜0.01）,且Cyclin D1表达从肠化生-不典型增生-腺癌组织依次增高（分别为50.04、 67.94、74.31）,差异有统计学意义（P＜0.01）。结论　Cyclin B1和 cyclin D1可以作为肿瘤进展标志物来评估Barrett食管患者进展为腺癌的危险性,并可能是食管腺癌发生过程中的早期事件。     

COX-2在Barrett食管与食管腺癌发病中的意义

目的：研究环氧化酶（COX-2）在Barrett食管（BE）及食管腺癌（EA）中的表达，探讨BE及EA的发病机制。方法：采用免疫组化染色及real—timePCR检测正常食管上皮、BE粘膜及EA标本中COX-2的蛋白及mRNA表达情况。结果：COX-2蛋白在正常鳞状上皮中几乎不表达，而在BE中呈轻中度阳性表达，在EA中呈弥漫强阳性表达，三者之间差异显著（P〈0．01），且呈线性趋势（r=0．810，P〈0．01）。COX-2mRNA在BE及EA中表达均增强，其表达率分别为正常鳞状上皮的1．3728倍（P〈0．01）和1．8312倍（P〈0．01）。结论：COX-2在BE及EA中表达升高，提示其表达的上调可能在BE及EA的发生发展中起重要作用。     

河南林州食管癌高发区反流性食管炎调查

目的 探讨河南食管癌高发区林州居民反流性食管炎(reflux esophagitis,RE)的流行特征,加深对食管癌变机理的了解.方法 采用统一RE问卷对河南省食管癌高发区508人进行逐一问卷调查.根据反流性食管炎的症状评分,≥12分为阳性诊断标准.结果 RE评分≥12分者28人(6%):女性RE检出率(4%,20/508)明显高于男性(2%,8/508)(P＜0.05).结论 女性RE发生率明显高于男性,与食管癌男性明显高于女性的性别分布相反,也明显低于西方国家RE发生率,提示可能RE与食管腺癌关系较与食管鳞癌关系密切.     

晚期糖化终产物受体在食管鳞癌组织中的表达及其意义

目的 探讨食管鳞癌组织中晚期糖化终产物受体(RAGE)的表达及意义.方法 采用免疫组化S-P法对50例食管鳞癌组织、30例癌旁不典型增生组织以及50例正常食管黏膜组织中RAGE蛋白表达进行检测;运用原位杂交方法对50例食管鳞癌组织、30例癌旁不典型增生组织以及50例正常食管黏膜组织中RAGE mRNA表达进行检测.结果食管鳞癌组织中RAGE蛋白、mRNA阳性表达率明显高于癌旁不典型增生组织及正常食管黏膜组织,三者两两比较差异均有统计学意义(P均＜0.05);食管鳞癌组织中RAGE蛋白、mRNA阳性表达率与肿瘤浸润深度、淋巴结转移有关(P均＜0.05).结论RAGE高表达可能与食管鳞癌发生和发展有关.     

食管鳞状细胞癌中CDH1基因启动子区甲基化状态与β-catenin异质表达的相关性

目的:研究食管鳞状细胞癌(Esophageal Squamous Cell Cancer,ESCC)中CDH1(cadherin 1)基因的甲基化状态,探讨其与Wnt中心因子β-catenin表达及与食管鳞癌发生的关系.方法:应用甲基化特异性PCR(MSP)及RT-PCR的方法检测91例食管鳞癌中CDH1基因的甲基化状态及其mRNA表达情况,应用免疫组织化学的方法检测β-catenin蛋白的表达情况,并分析与临床病理参数间的关系.结果:在91例食管鳞癌中,有72例CDH1基因发生了甲基化,甲基化率为79.1%,明显高于癌旁非肿瘤组织(P＜0.01);癌组织中CDH1基因的高甲基化与肿瘤患者的临床分期相关,与病理分级无关;癌组织中该基因mRNA的阳性表达率42.9%,明显低于癌旁非肿瘤组织(97.8%,P＜0.01);癌及癌旁组织中β-catenin蛋白的异质表达率分别为89.0%和24.2%,差异均有统计学意义(P＜0.01):癌组织中CDH1基因mRNA表达及β-catenin蛋白的异质表达均与该基因的甲基化状态明显相关(P＜0.05).结论:CDH1基因启动子区甲基化在食管鳞癌中频繁发生,该基因的高甲基化状态可能是引起食管鳞癌发生的分子机制之一,并有可能通过Wnt/β-catenin信号传导通路发挥作用.     

食管鳞状细胞癌组织中核干细胞因子蛋白和mRNA的半定量表达

目的 探讨食管鳞状细胞癌组织中核干细胞因子(NS)蛋白和mRNA的半定量表达情况.方法 应用免疫组化SABC法和逆转录聚合酶链反应(RT-PCR)法,检测62例食管鳞状细胞癌组织及其相对应的31例癌旁不典型增生组织和62例正常食管黏膜组织中NS蛋白和mRNA的半定量表达情况.结果 正常食管黏膜组织、癌旁不典型增生组织和食管鳞状细胞癌组织中,NS蛋白阳性表达率分别为17.7%(11/62)、41.9%(13/31)和69.4%(43/62),组间比较,差异有统计学意义(χ2=33.676,P＜0.01).食管鳞状细胞癌组织中,NS蛋白阳性表达率与其组织学分级、侵袭程度及淋巴结转移密切相关(均为P＜0.05),而与年龄、性别和病理分型无关(均为P＞0.05).食管鳞状细胞癌组织中,NS mRNA的相对含量(0.971±0.121)高于癌旁不典型增生组织(0.913±0.085)和正常食管黏膜组织(0.866±0.103),组间比较,差异有统计学意义(F=14.829,P＜0.01).不同组织学分级、不同侵袭程度及有无淋巴结转移的食管鳞状细胞癌组织之间,NS mRNA的相对含量差异均有统计学意义(均为P＜0.05),NSmRNA的相对含量与年龄、性别和病理分型无关(均为P＞0.05).结论 食管鳞状细胞癌组织中,NS mRNA的表达升高,其高表达与食管鳞状细胞癌的发生发展有关.     

EGFR mRNA上调在食管鳞状细胞癌患者预后预测中的意义

摘 要：［目的］ 探讨表皮生长因子受体（EGFR）基因突变和表达在食管鳞状细胞癌中的意义。［方法］ 分别应用real-time RT-PCR、免疫组化技术检测105例食管鳞状细胞癌组织中EGFR mRNA及蛋白表达水平,应用ADx-ARMS和PCR-Sanger测序法检测上述标本中EGFR基因18、19、20、21外显子突变,分析EGFR表达状态与临床、病理特征及患者生存期的关系。［结果］ 105例食管鳞状细胞癌组织中仅3例（2.9%,3/105）呈EGFR蛋白弱阳性表达,与癌旁组织相比无显著性差异（P>0.05）。92.4%（97/105）的食管鳞状细胞癌组织中EGFR mRNA表达水平上调,与癌旁组织相比有显著性差异（P=0.000）。且肿瘤组织EGFR mRNA表达水平分别与淋巴结转移（P=0.001）、神经浸润（P=0.039）及TNM分期（P=0.003）显著相关。Kaplan-Meier生存分析显示,EGFR mRNA表达水平上调患者的平均生存期（16.7个月）显著短于EGFR mRNA表达正常/下调患者（19.1个月）,其中8个EGFR mRNA正常表达病例生存情况均良好。多因素Cox回归分析表明,EGFR mRNA为食管鳞状细胞癌患者独立的预后因子,其相对危险度为1.368（P<0.001）。［结论］ EGFR mRNA可作为食管鳞状细胞癌患者预后标志物,其表达上调提示患者预后不良。     

食管鳞状细胞癌组织中去整合素-金属蛋白酶17mRNA表达的临床病理意义

 目的　探讨去整合素-金属蛋白酶17（ADAM17）mRNA在食管鳞状细胞癌中表达及其与临床病理因素的相关性。方法　采用反转录-聚合酶链反应（RT-PCR）半定量检测50例食管鳞状细胞癌及对应的正常食管黏膜中ADAM17 mRNA的表达。结果　50例食管鳞状细胞癌及对应的正常食管黏膜中ADAM17 mRNA的表达量分别为0.937±0.241、0.225±0.077,食管鳞状细胞癌组明显高于正常食管组（t＝-19.899,P＜0.01）。食管鳞状细胞癌中ADAM17 mRNA表达与淋巴结转移（t＝-4.703,P＜0.01）、TNM分期有相关性（t＝-2.652,P＜0.05）,与性别、年龄及组织学分级无相关性（t＝0.299、t＝-0.907、t＝-3.163,均P＞0.05）。结论　ADAM17 mRNA在食管鳞状细胞癌中高表达,在食管鳞状细胞癌的发生、侵袭转移中起重要作用,对判断食管鳞状细胞癌患者预后有一定的价值。     

Cyclin E、CDK2和p21WAF1在食管上皮癌变过程中的表达及意义

目的探讨食管上皮癌变过程中细胞周期调控因子cyclin E、CDK2和p21WAF1的表达状况及其意义.方法应用免疫组化SP法和原位杂交方法分别检测48例食管癌组织、31例非典型增生组织和17例正常食管粘膜中cyclin E、CDK2和p21WAF1蛋白及mRNA表达.应用半定量RT-PCR和Western blot检测22例新鲜食管癌及相应癌旁组织的mRNA和蛋白表达.结果从食管正常粘膜、非典型增生组织到癌组织,cyclin E和CDK2蛋白和mRNA阳性表达率逐渐上升,差异具有统计学意义(P＜0.01或P＜0.05).食管癌组织中cyclin E、CDK2和p21WAF1蛋白及mRNA高表达,与癌旁组织或切缘正常食管粘膜有显著性差异(P＜0.01).cyclin E、CDK2和p21WAF1基因表达显著正相关(P＜0.01或P＜0.05).结论食管上皮癌变过程中,细胞周期相关基因cyclin E和CDK2表达逐渐增强.cyclin E基因表达异常是食管癌变过程中的早期事件.p21WAF1基因在食管癌中高表达,可能与细胞周期调控的反馈机制有关.     

食管腺癌生物标记物的研究进展

 食管腺癌（esophageal adenocarcinoma，EAC）在西方国家发病率有逐年增加的趋势，往往伴随Barrett’S食管（Barrett’s esophagus，BE）的发生。Barrett’s化生已经被公认为是一种癌前病变，是发生食管腺癌的危险因素之一。预测腺癌发生最可靠的方法是从组织学上发现有高度的非典型性增生，对BE进行长期的内镜和组织学随访可预防食管腺癌的发生和获得早期发现。尽管EAC常伴随Barrett’s化生，但仍有大部分病人并不能从这种内镜检查中诊断出BE。 随着分子生物学的发展以及对BE 和EAC 流行病学研究的深入,人们逐渐探索生物标记物( biomarker) 在BE 和EAC 早期诊断和判断预后方面的重要意义。为了早期诊断EAC ,提高其生存率,最有希望的方法是对生物标记物的鉴定。从肿瘤发病的分子学角度看,对BE 和EAC 的生物标记物研究较多的主要有以下几类。     

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.