联合检测EB病毒相关抗体和抗原对诊断鼻咽癌的价值

背景与目的：近年来随着分子生物学的发展,提供了多项EB病毒（Epstein-Barrvirus）相关的检测指标。本研充通过同时检测EB病毒VCA-IgA、EA、IgA、EBV-特异性DNA酶（EBV-DNase）抗体、EB病毒DNA（EBV-DNA）,评价联合检测对诊断鼻咽癌的价值。方法：收集160例治疗前的鼻咽癌患者和76例健康成人的血清和血浆,应用免疫酶染色法检测血清VCA-IgA、EA-IgA：用正丁酸与巴豆油激发Raji细胞方法检测EBV-DNase抗体：用实时荧光定量聚合酶链反应（real-timefluoresc,eneequantitativePCR,RQ．PCR）分析血浆EBV-DNA,评什其在诊断鼻咽癌中的价值。结果：单项检测时对鼻咽癌患者诊断的敏感性和特异性分别为：VCA-IgA90．0％、89．5％,EA-IgA75．0％、94．7％,EBV-DNase抗体76．3％、90．8％,EBV-DNA68．8％、88．2％。联合检测的敏感性和特异性分别为98．8％和84．2％。VCA-IgA、EA-IgA阳性率与临床分期无关（P〉0．05）,各临床分期中EBV-DNase抗体阳性率、EBV-DNA水平与阳性率的差异有统计学意义（P〈0．05）。结论：VCA-IgA、EA-IgA、EBV-DNase和EBV-DNA单项检测时VCA-IgA敏感性最高,EA-IgA特异性最好;四项指标联合检测可提高鼻咽癌诊断的敏感性和准确度。EBV-DNase抗体、EBV-DNA有助于评估鼻咽癌病程和协助判断临床分期。     

生物素——链霉亲和素放大免疫酶法在鼻咽癌血清学检测中的应用

[目的] 探讨生物素--链霉亲和素放大免疫酶法(BSA)应用于鼻咽癌(NPC)IgA/EA血清学早期筛查效果,提高鼻咽癌早期诊断效率.[方法] 免疫酶法(IE)检测广西鼻咽癌示范基地血清中IgA/VCA(针对EBV壳抗原VCA的IgA型抗体),IgAVCA阳性者再用IE法及生物素--链霉亲和素放大免疫酶法(BSA)分别检测血清IgA/EA(针对EBV早期抗原EA的IgA型抗体),以临床病理检查结果为确诊标准.t检验及X2检验统计分析改进前后两种方法在鼻咽癌血清学早期检测方面的差异.[结果] IE法检测IgA/VCA阳性血清388例,IE法检测IgA/EA阳性率3.6%(14例),BSA法检测IgA/EA阳性率12.9%(50例),BSA法检出阳性率显著高于IE法(X2=22.070,P<0.001).在两种方法检测的血清IgA/EA均阳性的样品中,IgA/EA检测滴度的几何平均值(GMT)分别为1:17.04和1:51.87,BSA法显著高于IE法(t=2.804,P<0.05).进一步的病理检测确诊鼻咽癌患者16例,BSA法提高了NPC检测灵敏度(X2=16_347,P<0.001).[结论] 用生物素--链霉亲和素放大免疫酶法(BSA)检测血清EBV相关抗体特异性较高,并且可以提高鼻咽癌血清学早期检测的灵敏度,为在基层开展更有效的流行病学筛查提供了可行的方法.     

鼻咽癌患者血浆EBVDNA水平和VCA—IgA检测的临床意义

目的：探讨鼻咽癌患者血浆EBVDNA水平和VCA—IgA联合检测对鼻咽癌早期诊断的临床价值。方法：用荧光定量PCR方法检测血浆EBVDNA水平，常规免疫酶法检测VCA—IgA抗体滴度。结果：68例鼻咽癌患者中，EBVDNA阳性率95．59％，中位拷贝数93× 10^4 copies／ml，VCA—IgA抗体阳性率92．65％，抗体滴度≥1：20；其他头颈肿瘤36例中，EBVDVA阳性率5．56％，中位拷贝数为0copies／ml，VCA—IgA抗体阳率36．11％，阳性滴度均≤1：20；健康对照组EBVDNA阳性率为35．56％，其滴度除3例≥1：40外，余均≤1：20。鼻咽癌患者中EBVDNA和VCA—IgA抗体阳性率显著高于对照组。结论：进-步证实EBV与鼻咽癌有密切关系；EBVDNA水平和VCA—IgA抗体滴度联合检测，有助于鼻咽癌的早期辅助诊断。     

EB病毒免疫学对鼻咽癌诊断的价值

由于EB病毒和鼻咽癌密切相关,运用多项EB病毒免疫学指标(VCA—IgA,EA—IgA,EA—IgG,EBNA)对鼻咽癌进行研究,结果表明VCA—IgA,EA—IgA和EA—IgG对鼻咽癌均较特异,临床上可起到相互补充的作用,从而进一步提高鼻咽癌的诊断水平,减少假阳性;将VCA-IgA运用到高发危险区人群普查中,将有助于提高鼻咽癌早期发现率;合用抗朴体免疫酶法和细针穿刺法检查鼻咽癌颈转移癌细胞的EBNA,对于原发灶不明的颈块鉴别诊断和鼻咽原发灶隐蔽(To期)的鼻咽癌而又首先表现为颈转移者的诊断是有效的。     

广东四会鼻咽癌患者治疗前EB病毒VCA／IgA抗体水平与生存的关系

背景与目的：Epstein-Barr病毒VCA／IgA抗体（serum immunoglobulin Aagainst Epstein-Barr vires capsid antigen,EBV—VCA／IgA）是目前应用最广泛的鼻咽癌诊断指标之一,但它对鼻咽癌预后判断的意义尚不明确。本研究探讨VCA／IgA抗体水平与鼻咽癌患者长期生存的关系,为确立VCA／IgA能否作为鼻咽癌独立的预后指标提供依据。方法：根据广东省四会市肿瘤发病与死亡登记资料,选择1990至2003年在中山大学肿瘤防治中心治疗的全部317例四会籍初诊鼻咽癌患者,收集患者的临床与病理资料,分析患者治疗前血清VCA／IgA抗体不同水平与生存期的关系。结果：在临床分期中Ⅲ、Ⅳ期的抗体水平率较Ⅰ、Ⅱ期为高,P=0．01。抗体滴度越高的患者生存时间越短,低水平组（〈1：160）的患者（n=170）与高水平组（≥1：160）患者（n=147）的5年生存率分别为65．0％和43．0％,P=0．01。多因素分析显示患者的临床分期、性别、治疗年代和EBV-VCA／IgA水平是影响生存期的独立因素。结论：鼻咽癌患者治疗前VCA／IgA抗体水平可能是影响患者生存的独立预后指标。     

EB病毒抗体与鼻咽癌发病风险的前瞻性研究

[目的]探讨EB病毒抗体滴度变化与鼻咽癌发病风险的关系,为筛检高危人群提供依据.[方法] 1987～2007年对广东省四会市共18986名现场人群进行筛检,检测血清学EB病毒壳抗原免疫球蛋白(VCA/IgA)和早期抗原免疫球蛋白(EA/IgA)水平.采用Cox风险回归模型评估EB病毒抗体与鼻咽癌发病风险的关系.[结果] 1987～2007年共检出125例鼻咽癌.VCA/IgA和EA/IgA的血清阳性率分别为7.16％ (1318/18411)和0.24％ (45/18411).VCA/IgA阴性组鼻咽癌年龄调整发病率为29.4/10万人年,明显低于VCA/IgA阳性、EA/IgA阴性组(188.2/10万人年)和两者均阳性组(617.4/10万人年).与VCA/IgA阴性组相比,VCA/IgA阳性者抗体滴度越高,鼻咽癌发病风险越大.随访期间,EB病毒VCA/IgA抗体滴度升高者的鼻咽癌发病风险最高,在前5年的随访期间更为明显(调整HR=21.3,95％CI:7.1～64.1),抗体滴度降低者的发病风险最低(调整HR=1.5,95 ％CI:0.2～11.4).[结论]持续升高的VCA/IgA抗体滴度与鼻咽癌发病风险的增加明显相关,EB病毒VCA/IgA抗体阳性者是筛查的重点人群.     

鼻咽癌血清学检测中的复合阳性判断方法及其应用

EB病毒 (Epstein-Barr virus, EBV)与鼻咽癌的发生和发展密切相关 , 95% 以上的鼻咽癌血清都含有与 EB病毒壳抗原 (virus capscule antigen,VCA)相关的 IgA抗体 (IgA/VCA抗体 ). IgA/VCA(+ )人群被称为鼻咽癌的高危群体 [1]. 根据闵华庆等 [2]对 12万人的调查结果 , 在占总数 8.15% 的 IgA/VCA(+ )人群中 ,鼻咽癌的检出率比 IgA/VCA(- )人群高 40倍 . 尽管如此 , 在 IgA/VCA(+ )人群中鼻咽癌的阳性检出率仍然很低 , 只有 1.21% . 因此 , 有必要在 IgA /VCA(+ )人群中继续探索能提高鼻咽癌检出率和诊断准确性的方法 , 这也是关系到在鼻咽癌高发区如何提高血清学筛查效果的关键之一 . 1997年黄腾波等在广东四会鼻咽癌高发区对 IgA/VCA(+ )人群进行监测研究 , 提出了血清学与临床体检相结合的综合筛查方案 [3]. 当时检测 EBV早期复合抗原 (EBV-EA)相关 IgG抗体的酶联免疫吸附 (ELISA)法 (IgG/EA ELISA)尚未建立 . ELISA法与间接免疫酶染色 (IEA)检测 EBV-EA IgG抗体滴度的方法 (IgG/EA IEA)比较 , 在敏感性相同 (88.3% )的前提下 , 具有特异性 (98.3% )明显优于后者 (53.2% )的特点 [4] . 在特异性为 97.7% 的前提下 , 用 ELISA法检测鼻咽癌血清的敏感性 (89.2% )也显著高于用 IEA法测定 EBV-EA IgA抗体滴度 (IgA/EA IEA)的敏感性 (65.5% )[5].     

鼻咽癌患者的EB病毒IgM／VCA抗体反应的研究

本文应用免疫酶法检测了162例鼻咽癌、34例鼻咽癌粘膜病变、41例其他肿瘤和80例正常人(其中35例已知IgA/VCA抗体阳性)血清中IgM/VCA抗体,并与IgA/VCA和IgA/EA抗体进行比较。发现鼻咽癌患者血清中不仅含有高滴度的IgA/VCA抗体,而且含有高滴度的IgM/VCA抗体,阳性率(≥1:10)分别为97.53％和93.20％,GMT为157.60和95.75。两种抗体水平均明显高于其他对照组。有临床分期的62例鼻咽癌患者的IgM抗体水平,有随病程进展而略有升高的趋势。提示鼻咽癌患者体内的EB病毒慢性持续感染和活跃的复制。 鼻咽癌患者与IgA/VCA阳性的正常人血清中IgA/VCA和IgM/VCA抗体双阳性率分别为92.0％和31.43％;IgA/VCA和IgA/EA抗体双阳性率为48.76％和14.29％。鼻咽癌患者血清中,前者双阳性率高于后者双阳性率,且与正常相比有显著差异(P<0.01)。表明IgA/VCA和IgM/VCA抗体一起作为早期发现鼻咽癌的血清学指标,可能优于沿用的IgA/VCA和IgA/EA指标,操作和成本亦较方便和便宜。     

鼻咽癌高发区健康成人六项EB病毒抗体检测结果的分析

背景与目的：鼻咽癌有明显地域倾向性，而鼻咽癌发病又与EBV密切相关。本研究通过检测来自不同地域的人群抗EBV抗体的水平和阳性率．以探讨EBV感染与鼻咽癌的地域倾向性之间的关系。方法：从鼻咽癌高发区广东省中山市的健康成人中收集303例中山原住居民的血清和92例来自非NPC高发区的外省移民的血清，用ELISA法检测血清中的EBNA1-IgA、EBNA1-IgG、VCA-p18-IgA、VCA-p18-IgG、Zta—IgA和Zta—IgG等六种抗体水平，以校正相对吸光度（ArA）值表示，逐一比较两个人群样本六项抗EBV抗体水平及阳性率的差别。结果：中山原住居民的Zta—IgA（0．84±0．03）和VCA—p18-IgA的ArA（0．96±0．05）明显高于外省移民（0．42±0．04和0．40±0．05，P〈0．05）。另外，中山原住居民30-年龄段组和50～年龄段组的Zta—IgA阳性率分别是29．27％和48．28％，均明显高于外省移民同一年龄段组的3．03％和6．67％（P〈0．05）。中山原住居民30～年龄段组和50-年龄段组的VCA—p18．IgA分别是28．46％和43．10％，均明显高于外省移民同一年龄段组的9．09％和13．33％（P〈0．05）。结论：中山原住居民针对EBV溶解期的抗体Zta-IgA和VCA—p18-IgA的水平和阳性率偏高．反映其感染的EBV更多地处于再激活状态，这提示NPC高发区中山的原住居民罹患鼻咽癌的风险比来自非NPC高发区的外省移民更高。     

广西梧州市居民的鼻咽癌血清学普查

在广西梧州市进行了鼻咽癌的血清学普查,从年龄为40～59的居民12932人采血。VCA/IgA抗体的阳性率为5.3％,EA/IgA抗体的阳性率为VCA/IgA抗体阳性者的4.4％。VCA/IgA抗体阴性者的EA/IgA抗体也是阴性。从VCA/IgA抗体阳性者中检查出13例鼻咽癌,其中9例的EA/IgA抗体也是阳性。12932人群中的鼻咽癌检出率为100.5/10万,VCA/IgA抗体阳性者的鼻咽癌检出率为1900/10万,分别较1975—1978年同年龄组人群的年发病率高一倍和37倍。这些结果进一步证明EB病毒与鼻咽癌关系密切。13例鼻咽癌中Ⅰ期9例,占70％,Ⅱ期4例,占30％。因此,早期诊断和早期治疗可以降低病死率。     

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.