大肠肿瘤中Ezrin的表达及意义

目的:检测大肠癌及大肠腺瘤中Ezrin蛋白的表达,了解与大肠癌临床病理的相关因素。方法:采用SP免疫组化法,检测Ezrin蛋白在各组织中的表达及意义。结果:Ezrin在大肠癌、大肠腺瘤中的阳性表达率分别为69.4%(43/62)和40.0%(4/10),癌旁组织阳性表达率为32.6%(15/46),正常大肠组织阳性表达率为6.7%(1/15)。Ezrin的表达在正常大肠组织和大肠癌之间、大肠腺瘤和大肠癌之间以及癌旁组织和大肠癌之间均有显著性差异(P<0.05),而癌旁组织和大肠腺瘤之间Ezrin表达差异无显著性(P>0.05);Ezrin在大肠癌转移组及未转移组中的阳性表达率分别为89.7%(26/29)和51.5%(17/33);转移组阳性表达率高于未转移组(P<0.05);大肠癌组织中Ezrin的表达与患者年龄、性别、肿瘤发生部位、分化程度均无关(P>0.05)。结论:Ezrin的表达增高与大肠癌转移密切相关,可作为临床判断大肠癌转移及预后等生物学行为的重要参考指标。     

大肠癌COX-2与MMP-2的基因表达及其意义

目的探讨COX_2和MMP_2蛋白在大肠癌组织中的表达、相互关系及意义。方法采用链菌素亲生物素-过氧化物酶法(S_P法)检测68例大肠癌及20例正常大肠组织COX_2、MMP_2蛋白的表达情况。结果大肠癌组织COX_2的阳性表达为79.4%(54/68),正常大肠组织COX_2的阳性表达为10.0%(2/20),COX_2在大肠癌组织中的阳性表达显著高于正常组织(P<0.01);大肠癌组织中MMP_2的阳性表达为73.5%(50/68),正常大肠组织MMP_2阳性表达为20.0%(4/20),MMP_2在大肠癌组织中的阳性表达显著高于正常组织(P<0.01);在大肠癌组织中COX_2、MMP_2蛋白的表达之间存在显著正相关(γ=0.627,P<0.01)。结论大肠癌组织中存在COX_2、MMP_2的高表达,且两者之间的表达强度具有等级相关性。COX_2蛋白可通过诱导MMP_2蛋白的表达上调,增加大肠癌细胞的侵袭力,从而成为其促进大肠癌浸润、转移的途径之一。     

表皮-钙黏附素和Snail蛋白的表达与大肠癌侵袭转移及预后的关系

目的 研究表皮-钙黏附素(E-CD)和Snail蛋白在大肠癌组织中的表达及其与大肠癌侵袭、转移和预后之间的关系.方法 采用免疫组化EnVision法,检测E-CD和Snail蛋白在30例正常大肠黏膜、30例大肠腺瘤及142例大肠癌组织中的表达.结果 E-CD蛋白在正常大肠黏膜组织中的强阳性表达率为90.0%,明显高于其在大肠腺瘤和大肠癌组织中的强阳性表达率(63.3%和41.5%,P<0.05).Snail蛋白在大肠癌组织中的阳性表达率为52.1%,明显高于其在正常大肠黏膜和大肠腺瘤组织中的阳性表达率(6.7%和26.7%,P<0.05).E-CD蛋白的表达与大肠癌的分化程度、浸润深度、静脉侵犯、淋巴管侵犯、淋巴结转移以及Duke's分期有关(均P<0.05),而与患者的年龄、性别、肿瘤大小以及病理组织学类型无关(均P0.05).Snail蛋白的表达与大肠癌的分化程度、浸润深度、静脉侵犯、淋巴管侵犯、淋巴结转移、病理组织学类型以及Duke's分期有关(均P<0.05),而与患者的年龄、性别以及肿瘤大小无关(均P>0.05).E-CD蛋白与Snail蛋自在大肠癌组织中的表达呈负相关(r=-0.508).E-CD蛋白阳性表达者的术后1、3和5年生存率明显高于阴性表达者(P<0.05),Snail蛋白阴性表达者的术后1、3和5年生存率明显高于阳性表达者(P<0.05).淋巴结转移、Duke's分期、E-CD和Snail蛋白的表达可作为大肠癌独立的预后指标(均P<0.05).结论 E-CD和Snail蛋白的表达与大肠癌的侵袭、转移和预后明显相关,E-CD蛋白表达降低和Snail蛋白表达增强的大肠癌患者病期晚、预后差.     

良恶性大肠肿瘤组织血管内皮生长因子表达与意义

目的:研究血管内皮生长因子(VEGF)在大肠癌、大肠腺瘤和癌旁正常大肠黏膜标本中的表达,并探讨其表达与大肠癌发生、发展及转移的关系.方法:通过免疫组化SP法检测89例大肠癌、22倒大肠腺瘤、26例癌旁正常大肠黏膜标本中VEGF表达及与大肠癌临床病理特征的关系.结果:VEGF在大肠癌组织中的阳性率(71.9%,64/89)明显高于其在癌旁正常大肠黏膜组织(30.8%,8/26)、大肠腺瘤组织(40.9%,9/22)中的阳性率,差异有统计学意义(P<0.01);VEGF在大肠癌组织中的表达水平与肿瘤Dukes分期,有无淋巴结转移及患者年龄有关(P<0.05),与肿瘤组织学分级和患者性别无关.结论:VEGF表达升高与大肠癌的发生、发展、浸润及淋巴结转移有关,检测VEGF的表达情况有助于判断大肠癌的恶性程度及肿瘤预后.     

大肠癌组织中Cox-2和FasL的表达及意义

目的:探讨Cox2和FasL蛋白在大肠癌组织中的表达、相互关系及临床意义。方法应用免疫组化SP法检测60例大肠癌、20例大肠腺瘤及20例正常大肠组织Cox2和FasL蛋白的表达情况。结果:1)大肠癌组织、大肠腺瘤和正常大肠组织Cox2表达阳性率分别为78.3%(47/60)、55.0%(11/20)和25.0%(5/20),Cox2在大肠癌组织中阳性表达率显著高于腺瘤组织及正常大肠组织阳性表达率,P=0.000。大肠癌、大肠腺瘤和正常大肠组织阳性表达率分别为86.7%(52/60)、50.0%(10/20)和20.0%(4/20)FasL在大肠癌组织中阳性表达率显著高于腺瘤组织及正常组织,P=0.000。2)Cox2和FasL的表达与肿瘤组织学分级及肿瘤生长部位无关Cox2与肿瘤Duke’s分期和淋巴结转移有相关性,P值分别为0.0.25和0.006。Cox2的表达与肿瘤大小有关,P=0.005。3)大肠癌组织中Cox2与FasL蛋白的表达为正相关性,r=0.627,P=0.000。结论:大肠癌组织中Cox2和FasL高表达,两者之间的表达强度有等级相关性。Cox2蛋白可通过诱导FasL蛋白的表达上调,增加大肠癌细胞侵袭力,从而成为其促进癌细胞浸润、转移的途径之一。     

nm23 VEGF-C及VEGFR-3在大肠癌中的表达及意义

目的:探讨nm23、VEGF-C及其受体VEGFR-3在大肠癌中的表达和三者间的相互关系,及其在大肠癌淋巴结转移和肿瘤进展中的意义.方法:采用免疫组化SP法检测97例大肠癌组织和97例正常大肠组织中nm23、VEGF-C及VEGFR-3的表达.结果:1)A、B期大肠癌及无淋巴结转移的大肠癌组织中nm23的阳性表达率分别为68.9%、68.2%,C、D期及有淋巴结转移的大肠癌组织中nm23阳性表达率分别为30.6%、25.8%,A、B期高于C、D期,无淋巴结转移高于有淋巴结转移,差别有统计学意义(P<0.05);VEGF-C阳性表达率在C、D期及有淋巴结转移的大肠癌组织中分别为75.0%、77.4%,在A、B期及无淋巴结转移的大肠癌组织中分别为49.2%、50.0%,两者比较,差别有统计学意义(P<0.05);VEGFR-3在C、D期及有淋巴结转移的大肠癌中的阳性表达率分别为63.9%、67.7%,在A、B期及无淋巴结转移的大肠癌组织中分别为41.0%、40.9%,差别有统计学意义(P<0.05.2)nm23与分化程度、肠壁侵犯深度、有无淋巴结转移及Duckes分期有关(P<0.05),VEGF-C及VEGFR-3与分化程度、淋巴结转移及Duckes分期有关(P<0.05).3)nm23在正常大肠组织和大肠癌组织中的阳性表达率分别为83.5%、54.6%,差别有统计学意义(P<0.05),VEGF-C在正常大肠组织和大肠癌组织中的阳性表达率分别为29.9%、58.8%,差别有统计学意义(P<0.05),VEGFR-3在正常大肠组织和大肠癌组织中的阳性表达率分别为21.6%、49.5%,两者比较,差别有统计学意义(P<0.05).结论:nm23与VEGF-C和VEGFR-3在大肠癌中的表达呈负相关关系,nm23基因时大肠癌有抑制作用,VEGF-C和VEGFR-3与大肠癌的侵袭和转移密切相关,三者的联合检测可作为评价大肠癌病情、推测预后及指导治疗的重要参考指标.     

鼻咽癌组织中MIF、c-Fos、NF-κB和MMP9的表达及意义

目的研究巨噬细胞移动抑制因子(macrophage igration nhibitory actor,MIF)、核蛋白c-Fos、核因子κB F-κB)以及金属基质蛋白酶9(MMP9)在鼻咽癌组织中的表达水平及相互关系,探讨MIF在鼻咽癌细胞早期侵袭转移过程中的作用及相关机制.方法收集1999～2003年期间45例确诊未治的鼻咽原发癌活检组织标本,采用免疫组化法检测鼻咽癌组织中MIF、c-Fos、NF-κB 65亚单位以及MMP9的表达,并分析与患者的病理及临床资料的关系.结果在45例鼻咽原发癌组织中,MIF、c-Fos、NF-κB 65和MMP9的阳性表达率分别为77.8%(35/45)、51.1% 3/45)、62.2％(28/45)和71.1％(32/45).其中,癌细胞MIF和MMP9的表达水平均与淋巴结转移有关,伴有淋巴结转移的癌组织中两者表达水平均高于无淋巴结转移的癌组织(P值均＜0.05).MIF阳性组的癌细胞c-Fos和MMP9的表达也均显著高于MIF阴性病例.且MIF、c-Fos和MMP9的表达互为正相关.但癌细胞NF-κB 65的表达与患者性别、年龄、病理组织学分型、有无淋巴结转移以及临床分期均未显示相关性,且与其它3种蛋白的表达亦无相关性.结论 MIF在鼻咽癌细胞的早期淋巴结转移过程中可能具有重要的促进作用,其机制可能是非NF-κB依赖性的,而与增强癌细胞c-Fos表达、活化AP-1转录因子间接地调控癌细胞MMP9表达上调有关.     

大肠癌组织中MMP-3的表达及其临床意义

目的:探讨基质金属蛋白酶3(matrixmetalloproteinases3,MMP3)在大肠腺瘤及大肠癌组织中的表达及其与临床各病理参数之间的关系。方法:应用免疫组织化学方法检测MMP3在20例大肠腺瘤和60例大肠癌组织中的表达。结果:MMP3在20例大肠腺瘤及60例大肠癌组织中,阳性表达率分别为10.0%(2/20)和41.7%(25/60),组间差异有统计学意义,P=0.031;在大肠腺癌组织中,MMP3的阳性表达与淋巴结转移呈正相关,P=0.008,与患者5年生存率呈负相关,P=0.003。结论:MMP3的上调表达可能参与了大肠癌的发生与发展,对临床上判断预后具有较大的意义。     

垂体肿瘤转化基因在大肠正常黏膜、腺瘤及大肠癌组织中的表达及意义

目的探讨垂体肿瘤转化基因(PTTG)的表达与大肠癌发生、发展的关系。方法采用反转录聚合酶链式反应(RT-PCR)技术及免疫组织化学法检测20例大肠正常黏膜、20例大肠腺瘤、80例大肠癌组织中PTTG mRNA及蛋白的表达水平。结果大肠癌组织中PTTG mRNA及蛋白的表达量明显高于大肠腺瘤和正常黏膜组织(P均<0.01),大肠腺瘤组织亦高于正常黏膜组织(P<0.01),且PTTG mRNA及蛋白的表达量与大肠癌浸润深度、淋巴结转移呈正相关。结论PTTG的高表达在大肠癌的发生、发展过程中起到重要作用,可作为判断大肠癌发生发展的预测因素。     

大肠肿瘤中Ezrin的表达及意义

目的：检测大肠癌及大肠腺瘤中Ezrin蛋白的表达,了解与大肠癌临床病理的相关因素。方法：采用SP免疫组化法,检测Ezrin蛋白在各组织中的表达及意义。结果：Ezrin在大肠癌、大肠腺瘤中的阳性表达率分别为69.4%（43/62）和40.0%（4/10）,癌旁组织阳性表达率为32.6%（15/46）,正常大肠组织阳性表达率为6.7%（1/15）。Ezrin的表达在正常大肠组织和大肠癌之间、大肠腺瘤和大肠癌之间以及癌旁组织和大肠癌之间均有显著性差异（P〈0.05）,而癌旁组织和大肠腺瘤之间Ezrin表达差异无显著性（P〉0.05）;Ezrin在大肠癌转移组及未转移组中的阳性表达率分别为89.7%（26/29）和51.5%（17/33）;转移组阳性表达率高于未转移组（P〈0.05）;大肠癌组织中Ezrin的表达与患者年龄、性别、肿瘤发生部位、分化程度均无关（P〉0.05）。结论：Ezrin的表达增高与大肠癌转移密切相关,可作为临床判断大肠癌转移及预后等生物学行为的重要参考指标。     

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.     

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.     

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.     

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。     

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。     

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.     

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.     

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.