核因子-κB及Bcl-2基因在肝外胆管癌组织中表达及意义

目的研究核因子κB(NF-κB)及抗凋亡基因Bcl-2在肝外胆管癌组织中的表达及意义。方法应用免疫组织化学SABC法,检测NF-κB在48例肝外胆管癌组织及12例正常肝外胆管组织中的表达变化及抗凋亡基因Bcl-2的相应表达,并分析其与肝外胆管癌临床病理的关系。结果NF-κB在肝外胆管癌组织及正常胆管组织中的阳性表达率分别为75%、16.7%,两者有显著性差异(P<0.01);Bcl-2在肝外胆管癌组织及正常胆管组织中的阳性表达率分别为64.6%、8.3%,两者有显著性差异(P<0.01)。NF-κB的阳性表达在病理分级间有显著性差异(P<0.01)且与Bcl-2的阳性表达显著相关。结论NF-κB是一种与肝外胆管癌有关的癌蛋白,其与Bcl-2高度相关,表明NF-κB可能通过对下游抗凋亡基因表达的调控,参与了肝外胆管癌的抗凋亡过程,影响肝外胆管癌的发生发展。     

Bag-1及Bcl-2在前列腺癌组织中的表达及意义

目的探讨基因Bag-1和Bcl-2在前列腺癌中的表达及其与前列腺癌的关系。方法选取第四军医大学西京医院2002年~2005年未经治疗的前列腺癌组织标本45例,前列腺增生10例,采用免疫组化SABC法检测标本中Bag-1及Bcl-2的表达,并探讨Bag-1及Bcl-2的表达与前列腺癌分期、分级及预后的关系。结果Bag-1在前列腺癌组织中表达率为62.2%,前列腺增生组织中20.0%。Bag-1与肿瘤分级、分期及预后密切相关(P<0.05),随前列腺癌恶性程度增加,其表达强度也增加。Bcl-2在前列腺癌组织中阳性表达率为77.8%,与前列腺增生组织20.0%相比,有显著性差异(P<0.05),但其表达与不同病理细胞类型、病理分级及临床分期无关(P>0.05)。Bag-1与Bcl-2的表达正相关(P<0.05)。结论前列腺癌组织中Bag-1表达可作为预后指标;Bcl-2可能参与前列腺组织由良性向恶性转化的过程,但与癌细胞恶性分化程度无关。     

肝外胆管癌Bmi-1、Mdm2和Ki-67的表达及其临床意义

 目的　探讨Bmi-1、Mdm2和Ki-67蛋白在肝外胆管癌中的表达及临床意义。方法　采用免疫组织化学方法检测30例肝外胆管癌组织中和10例正常胆管上皮组织中Bmi-1、Mdm2和Ki-67蛋白表达情况,分析其与临床病理特征的关系。结果　Bmi-1在正常胆管上皮组织中均呈阴性表达,而在肝外胆管癌组织中18例呈阳性表达,阳性表达率60.0 %,明显高于正常胆管上皮组织（P＜0.05）。胆管癌组织中Mdm2的阳性表达率为56.7 %（17例）,明显高于正常胆管上皮组织的20.0 %（2例）（P＜0.05）。正常胆管上皮组织Ki-67标记的增殖指数均<1 %,而在肝外胆管癌组织中18例Ki-67标记的增殖指数≥5 %,在肝外胆管癌组织的增殖活性明显高于正常胆管上皮组织（P＜0.05）。且肝外胆管癌组织Bmi-1和 Mdm2的表达呈正相关。不同临床病理特征在肝外胆管癌组织中Bmi-1、Mdm2和Ki-67表达差异无统计学意义。结论　肝外胆管癌组织增殖活性及Bmi-1和Mdm2蛋白表达均明显增高,Bmi-1和Mdm2过表达可能与肝外胆管癌发生有关。胆管癌组织中Bmi-1、Mdm2和Ki-67表达与患者临床病理特征无关。     

肝外胆管癌组织MMP-2表达及其临床意义

目的 MMP-2是基质金属蛋白酶(matrixmetalloproteinase,MMPs)家族中最主要的家族成员,因其可以降解细胞外基质,使癌细胞能够顺利穿透细胞外基质和基底膜组成的屏障,浸润其临近的纤维结缔组织,进而发生远处转移.本研究探讨MMP-2在肝外胆管癌及正常胆管组织中的表达水平及其临床意义.方法 收集济宁医学院附属湖西医院2005-11-01-2010-04-30肝外胆管癌手术切除蜡块标本共61例为研究对象,选取同期胆管正常组织标本35例作为对照.采用免疫组化方法检测61例肝外胆管癌及35例胆管正常组织中MMP-2蛋白的表达情况,统计分析MMP-2蛋白和患者临床病理特征及预后相关性.结果 肝外胆管癌组中MMP-2阳性表达率73.77%(45/61),显著高于胆管正常组织的5.71%(2/35),差异有统计学意义,P<0.001.不同性别、年龄、肿瘤分化程度、淋巴结转移和TNM分期肝外胆管癌组织中MMP-2表达水平差异有统计学意义,均P值<0.05.MMP-2阴性肝外胆管癌患者术后1、3和5年生存率分别为82.00%、55.00%和25.00%,MMP-2阳性肝外胆管癌患者术后1、3和5年生存率分别为33.00%、9.00%和0,两组生存率差异有统计学意义,χ2=16.556,P<0.001.结论 MMP-2的表达与肝外胆管癌发生、发展和浸润转移相关,可能在肝外胆管癌的浸润转移中发挥重要作用.MMP-2有望成为新的肝外胆管癌的肿瘤标志物,为预后判断和制定相应的治疗方案提供依据.     

Survivin和Bcl-2蛋白在乳腺癌中的表达及意义

[目的]分析Survivin和Bcl-2蛋白在乳腺癌中的表达及其与临床病理特征的关系.[方法]采用免疫组织化学PV法检测Survivin和Bcl-2在38例浸润性乳腺癌及10例乳腺正常组织中的表达情况,分析乳腺癌患者中Survivin和Bcl-2的表达与临床病理特征的关系,以及两者间的相关性.[结果]乳腺癌患者中Survivin蛋白阳性表达率(86.84％)明显高于乳腺正常组织(10.00％),差异有统计学意义(P＜0.05).Survivin蛋白的表达与淋巴结转移有关(P＜0.05).乳腺癌患者中Bcl-2阳性表达率(65.79％)亦明显高于乳腺正常组织(20.00％)(P＜0.05),Bcl-2表达与组织学分级有关(P＜0.05).Survivin 和Bel-2蛋白的表达无相关性(P＞0.05).[结论]Survivin、Bcl-2蛋白在乳腺癌的诊断及预后判断方面具有重要意义.     

PEDF与VEGF在肝外胆管癌中的表达及意义

目的:探讨色素衍生上皮因子(PEDF)及血管内皮生长因子(VEGF)表达与肝外胆管癌的关系,并对胆管癌组织中两者的相关性进行初步研究。方法:收集中国医科大学附属盛京医院普通外科于2006年1月-2010年5月手术切除并经病理证实的肝外胆管癌标本70例。30例正常胆管组织取自胆囊结石患者行胆囊切除且无炎症状态的胆囊管组织。用免疫组织化学方法检测PEDF及VEGF的表达情况,统计学处理采用SPSS19.0软件,组间关系采用单因素方差分析,相关关系分析采用Spearman等级相关分析法。结果:PEDF表达于细胞膜和细胞浆,以细胞膜和细胞浆出现棕黄色为阳性表达,其在胆管癌组织中有阴性或弱阳性表达,在正常胆管组织中有阳性表达。VEGF表达于细胞浆,以细胞浆出现棕黄色或棕褐色颗粒为阳性表达,其在胆管癌组织中有阳性表达,在正常胆管组织中为阴性或弱阳性表达。在胆管癌组织中PEDF与VEGF的表达呈负相关。PEDF和VEGF在胆管癌中的表达与有无淋巴结转移及肿瘤分期有关,而与肿瘤大小、分化程度无关。结论:PEDF表达减少或VEGF表达增高与胆管癌的发生、发展及侵袭转移有关。PEDF与VEGF在胆管癌的发生和发展中起到相反的作用。     

Bcl-2和Beclin-1在肝癌组织中的表达及其相关性

目的:探讨Bcl-2和Beclin-1在肝癌(hepatocellular carcinoma,HCC)患者术后复发中的作用,并分析肝癌组织中Bcl-2和Beclin-1的蛋白表达是否具有相关性。方法:收集肝癌组织114例,采用免疫组织化学法检测各组中 Bcl-2蛋白和Beclin-1蛋白的表达情况。与患者临床资料进行统计学分析。结果:利用χ2检验发现Bcl-2在HCC中的表达仅与患者的肿瘤个数程度相关,Beclin-1在HCC中的表达仅与患者的肿瘤分化程度相关,差异具有统计学意义。HCC中Bcl-2和Beclin-1蛋白的表达呈负相关（r =-0.61,P＜0.000 1）。Bcl-2表达阳性影响患者的预后(Log-rank=8.892,P=0.002 9),Beclin-1表达阴性影响患者的预后(Log-rank=5.350,P=0.020 7)。多因素分析显示肿瘤的肝内复发与肝内肿瘤个数、Bcl-2表达有关。结论:Bcl-2和Beclin-1在肝癌中具有相关性,共同影响患者的预后。     

胆管癌组织Smad7表达预后价值分析

目的:研究Smad7及上皮间质转化(EMT)相关标志在胆管癌组织中的表达及与临床病理因素的关系.方法:采用免疫组化检测41例胆管癌和癌旁组织中Smad7、E-cadherin和Vimentin的表达,同时结合临床病理资料及临床预后进行分析.结果:41例胆管癌组织中Smad7、Vimentin的阳性表达率[68.3％(28/41)、70.7％(29/41)]及E-cadherin 缺失率[51.2％(21/41)]明显高于相应癌旁组织[30.0％(3/10)、30.0％(3/10)和10.0％ (1/10)];Smad7、Vimentin和E-cadherin的表达与淋巴结转移、神经脉管浸润差异有统计学意义,P＜0.05;而与性别、年龄、肿瘤部位、肿瘤类型和肿瘤分化程度等无关,P＞0.05.胆管癌组织中E-cadherin的缺失及Vimentin的阳性表达与Smad7表达有相关性,P值分别为0.013和0.018;Smad7高表达者往往术后无病生存期及总生存期均较短,P值分别为0.044、0.034.结论:胆管癌在其癌变与浸润转移过程中可能发生了EMT现象,Smad7蛋白在胆管癌组织中会随进程发展而增加,可能与Smad信号通路激活,机体反馈性调节增加有关,且其有望做为一种顸后指标应用于临床评估.     

B7-H1和Bcl-2在人结直肠癌中表达及其临床意义

目的:分析B7-H1及Bcl-2蛋白在人结直肠癌中的表达,并探讨其与结直肠癌临床病理特征之间的关系.方法:用免疫组织化学法检测57例手术切除的结直肠癌组织标本及癌旁正常组织标本中B7-H1及Bcl-2的表达,并结合临床病理特征进行相关性分析.结果:与癌旁正常组织相比,B7-H1及Bcl-2在结直肠癌组织中的阳性表达率明显高于癌旁组织,差异有统计学意义(P＜0.05).Bcl-2及B7-H1在结直肠癌组织中的表达均与分化程度呈负相关(P＜0.01),而且B7-H1在有淋巴结转移组(Dukes分期C+D)与无淋巴结转移组(Dukes分期A+B)相比,阳性表达率升高,差异有统计学意义(P＜0.05).另外,在高-中分化的结直肠癌组织中,B7-H1阴性组Bcl-2阳性表达率明显高于B7-H1阳性组,差异有统计学意义(P＜0.01).短期随访中,死亡的患者均B7-H1表达阳性.结论:B7-H1表达与结直肠癌的侵袭转移及生存期相关,且在高-中分化肿瘤组织中,提示与Bcl-2联合检测可能对结直肠癌的诊断、治疗及预后评价有一定的临床意义.     

B7-H1和Bcl-2在上皮性卵巢癌中的表达及其临床意义

目的 探讨B7-H1与Bcl-2在上皮性卵巢癌组织中的表达及其与上皮性卵巢癌临床病理特征之间的关系.方法 应用免疫组织化学法检测手术切除的80例上皮性卵巢癌组织及20例正常卵巢组织蜡块中B7-H1及Bcl-2的表达情况,并分析其表达与不同临床病理特征之间的相关性.结果 上皮性卵巢癌组织B7-H1及Bcl-2阳性表达率分别为77.5％ (62/80)和58.8％ (47/80),均高于正常卵巢组织的15.0％ (3/20)和10.0％ (2/20),差异有统计学意义(x2=27.473,P＜0.05;x2=15.216,P＜0.05).Bcl-2及B7-H1在上皮性卵巢癌组织中的表达均与分化程度呈负相关(x2=9.367,P＜0.01;x2=11.702,P＜0.01),而且Bcl-2与国际妇产科联合会分期呈正相关(x2=7.766,P＜0.01).另外,在上皮性卵巢癌组织中B7-H1和Bcl-2阳性表达之间呈正相关(r =0.400,P＜0.01).结论 B7-H1和Bcl-2在上皮性卵巢癌组织中表达明显上调,二者存在正相关性,与上皮性卵巢癌的发生、发展有关,联合检测B7-H1和Bcl-2可能对上皮性卵巢癌的诊治有一定的指导作用.     

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.     

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.     

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.     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

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。     

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.     

肾上腺素能β受体与肿瘤生长及转移

大量研究表明肿瘤细胞可表达β受体，而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移，β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路，提供了新的治疗靶点。     

Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance

This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.