胃癌组织中环氧合酶-2表达及其与P-gp表达相关性的研究

目的 :探讨环氧合酶 2 (COX 2 )蛋白在胃癌组织中的表达 ,并探讨COX 2对P糖蛋白 (P gp)表达的影响。方法 :应用免疫组织化学方法检测 4 8例胃癌及 10例正常胃组织中COX 2蛋白与P gp蛋白的表达。结果 :正常胃组织中未见COX 2表达 ,胃癌组织中COX 2阳性率为 6 0 .4 % (2 9/ 4 8) ,其阳性表达与肿瘤的TNM分期及淋巴结转移相关 (P <0 .0 5 )。COX 2阳性组中P gp表达阳性率为 82 .8% (2 4 / 2 9) ,而COX 2阴性组P gp同时阴性率 6 3.2 %(12 / 19) ,两者有高度正相关性 ,相关系数r=0 .4 70 (P <0 .0 1)。结论 :COX 2蛋白的表达参与胃癌的发生及恶性进展 ,并可能干预P gp表达 ,参与对肿瘤的多药耐药 (MDR)的调节作用     

Survivin在胃癌中的表达及其与COX-2相关性的研究

目的 :探究凋亡抑制基因survivin在胃癌组织中的表达与COX 2表达的相关性。方法 :运用S P免疫组化技术 ,检测survivin和COX 2蛋白在 93例胃癌组织、2 0例正常胃黏膜组织以及胃癌细胞株MGC 80 3中的阳性率。结果 :survivin蛋白在 2 0例正常胃黏膜组织中阴性 ,而 93例胃癌组织中有 66例阳性 ,占 71% ,差异有显著性 (P <0 .0 1) ,COX 2蛋白在胃癌组织中的阳性率为 76.3 % ,MGC 80 3细胞中survivin和COX 2蛋白均阳性。Survivin蛋白阳性率与胃癌组织的分化程度、淋巴结转移、TNM分期相关 ,而与浸润程度不相关 ,并与COX 2蛋白阳性呈正相关 (Pearson列联系数 0 .2 2 7P <0 .0 5)。结论 :肿瘤组织中survivin蛋白的特异性阳性在胃癌的发生发展中起重要作用 ;survivin蛋白与胃癌组织中COX 2蛋白的阳性密切相关 ,两者可能存在共同的激活机制 ,构成抑制胃癌细胞凋亡的多种途径     

胆囊癌组织中环氧合酶-2和P-耐药糖蛋白的表达及其相关性研究

目的 :探讨环氧合酶 -2 (COX 2 )和P -耐药糖蛋白 (P gp)在胆囊癌组织中表达的临床病理意义和相关性。方法 :采用免疫组织化学方法 (SP法 )检测64例胆囊癌组织标本中COX 2和P gp蛋白的表达。结果 :胆囊癌组织中COX 2和P gp蛋白的阳性率分别为 71 9% ( 4 6/ 64 )和 65 6% ( 4 2 / 64 ) ,显著高于癌旁正常组织中两者的阳性率 4 8% ( 2 / 42 )和 7 1%( 3 / 42 ) ,P <0 0 5 ,P =0 0 0 6。COX 2的表达与胆囊癌临床分期、淋巴结转移及患者的预后密切相关 ,P <0 0 5 ,P =0 0 0 0、0 0 0 0、0 0 1,而与组织学分级无关 ;P gp的表达与淋巴结转移及患者的预后密切相关 ,P <0 0 5 ,P =0 0 0 2、0 0 0 1,而与组织学分级、临床分期无关 ;二者的表达与患者的性别、年龄、肿瘤的大小均无关。COX 2与P gp的表达调控呈正相关 ,两者的表达水平呈正相关性 ,r =0 42 5 ,P<0 0 5。结论 :在胆囊癌中 ,COX 2、P gp参与肿瘤发生发展过程并与患者的预后有关 ,COX 2和P gp的协同作用在肿瘤多药耐药的形成中起着重要作用 ,选择性COX 2抑制剂的应用会预防肿瘤耐药并提高化疗的疗效     

胃癌及胃溃疡组织中环氧合酶2的表达

目的　探讨环氧合酶 2 (cyclooxygenase 2 ,COX 2 )蛋白在胃癌组织、正常胃黏膜组织以及胃溃疡组织中的表达及其意义。方法　应用免疫组化方法 (SP法 )检测 3 6例胃癌组织及其癌旁正常胃黏膜组织以及 12例胃溃疡组织中COX 2蛋白的表达。结果　胃癌组织中COX 2蛋白的表达水平显著高于癌旁正常胃黏膜及胃溃疡组织 ,差异具有显著性 (P <0 0 1) ;有淋巴结转移的胃癌组织中COX 2蛋白的表达水平高于无淋巴结转移者 ,差异具有显著性 (P <0 0 5 ) ;Ⅲ Ⅳ期胃癌组织的COX 2蛋白的阳性表达水平明显高于Ⅰ Ⅱ期 ,差异具有显著意义 (P <0 0 5 )。结论　COX 2蛋白的过表达参与了胃癌的演进。     

胃癌组织中环氧化酶-2的表达与微血管密度和VEGF的关系

目的 :探讨环氧化酶 -2 (COX 2 )在胃癌组织中的表达及其与微血管密度(microvesseldensity ,MVD)和血管内皮生长因子 (vascularendothelial growthfactor ,VEGF)的关系。方法 :采用免疫组织化学法 ,检测 43例胃癌患者手术切除标本中COX 2和VEGF的表达 ,并计数MVD。结果 :COX 2在胃癌组织的阳性表达率为60 5 % ,明显高于对照组 ,P <0 0 1;并且与胃癌淋巴结的转移和临床分期有关 ,与肿瘤大小、浸润深度、分化程度均无关。COX 2和VEGF表达一致符合率为 5 3 5 % ,两者表达有显著相关性 ,P <0 0 1。COX 2阳性和VEGF阳性组MVD值 (2 2 0 8± 3 69、2 2 12± 3 5 0 )均高于COX 2阴性和VEGF阴性组 (17 68± 3 5 0、16 15± 3 2 3 ) ,P <0 0 5 ;COX 2和VEGF均为阳性者的MVD值最高 (2 2 86± 3 40 ) ,P <0 .0 5。结论 :COX 2、VEGF的表达以及MVD的测定可作为判断胃癌恶性潜能的重要生物指标。COX 2、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测COX 2、VEGF的表达对了解肿瘤血管形成的机制有一定的作用     

环氧合酶-2对胃癌血管内皮生长因子及血管形成的影响

 目的　探讨环氧合酶 2 (COX 2 )对胃癌血管内皮生长因子 (VEGF)的表达及血管生成的影响。方法　应用免疫组织化学技术检测胃癌组织中COX 2 ,VEGF表达和微血管密度 (MVD)。结果　COX 2在62 .2 %胃癌组织中表达增高 ,COX 2表达与VEGF表达显著相关 (γS=0 .5 85 ,P <0 .0 1 ) ,且COX 2和VEGF均阳性的胃癌组织MVD(64.0± 2 5 .4)亦明显高于两者均阴性者 (3 0 .7± 1 1 .5 ) (P <0 .0 1 )。结论　胃癌组织中存在COX 2的高表达 ,COX 2通过增加VEGF表达而促进肿瘤血管形成     

不同部位胃组织Fas/FasL表达的研究

目的 :研究Fas/FasL在同一胃癌患者不同部位胃组织中的表达 ,并探讨其与临床病理学特征的关系。方法 :利用免疫组化法对 5 0例同一患者胃癌组织、癌旁交界组织、距肿瘤边缘 5cm处、正常组织的Fas/FasL表达进行检测 ,检验上述组织中Fas/FasL表达的差异。结果 :比较肿瘤组织、癌旁交界组织与正常组织Fas的阳性表达率 ( 10 0 % )和FasL的阳性表达率 ( 0 )差异均有统计学意义 ,P <0 0 5。距肿瘤边缘 5cm处( 96% )与正常组织 ( 10 0 % )的Fas阳性表达率和FasL的阳性表达率差异无统计学意义 ,P >0 0 5。而不同分化的肿瘤组织中Fas/FasL表达差异无统计学意义 ,P >0 0 5。结论 :胃癌中存在Fas表达的下调和FasL表达的上调 ,Fas/FasL系统可能参与了胃癌细胞的免疫逃避机制     

P-糖蛋白在常见恶性肿瘤组织中表达的研究

 目的　探讨临床常见恶性肿瘤组织P 糖蛋白 (P gp)的表达情况 ,指导临床实践。 方法　收集我院 2 0 0 1年 10月～ 2 0 0 2年 10月术前未经化疗及放疗的切除标本 2 6 3例 ,以S P免疫组化方法检测其P gp表达情况。 结果　食管癌、胃癌、大肠癌、肺癌、宫颈癌P gp表达阳性率分别为6 4 .7%、88.0 %、85 .7%、6 1.3%、6 0 .5 %。胃癌、大肠癌P gp表达阳性率明显高于其他癌 ,腺癌P gp表达阳性率明显高于鳞癌及其他癌。结论　P gp在临床常见恶性肿瘤组织中有较高的原发表达 ,检测肿瘤组织 (尤其是胃肠道腺癌 )的P gp对选择合理的化疗方案和判断预后有重要作用。     

胃癌组织中P-gp和P53蛋白表达的比较研究

目的　探讨P gp和P 5 3蛋白在胃癌中的表达意义及它们的相关性。方法　应用S P免疫组化方法 ,分析 60例胃癌组织中P gp和P 5 3蛋白的阳性表达情况。结果　 60例胃癌组织中P gp和P 5 3蛋白阳性表达分别为 5 8 3 3 % ( 3 5 /60 )和 5 0 .17% ( 3 1/60 )。P gp和P 5 3蛋白共同阳性表达率为 67.74% ( 2 1/3 1)。P gp表达与组织分化程度及TNM临床分期均无显著性差异 (P >0 0 5 ) ,P 5 3蛋白表达则与胃癌组织的分化程度、临床分期密切相关 ,且差异有显著性 (P <0 0 5 )。结论　P gp与P 5 3蛋白表达有相关性。     

E-钙黏附素和基质金属蛋白酶-2的表达变化及与胃癌侵袭和转移的关系

目的 :探讨E cadherin和MMP 2在胃癌组织中的表达与胃癌浸润转移的相关性。方法 :采用S P免疫组化染色 ,检测 83例胃癌组织的E cadherin和MMP 2的表达情况 ,2 0例胃良性病变手术病例作对照。结果 :正常胃黏膜E cadherin呈强阳性表达 ,胃癌组织中E cadherin表达率明显减低 ,阳性表达率为 16 9% (14 83) ;E cadherin表达减低与胃癌细胞分化程度、浸润深度、浸润型生长、淋巴结转移密切相关 (P <0 0 5 ) ,而与TNM分期及肿瘤大小无关。MMP 2在正常胃黏膜中呈阴性表达 ,在胃癌组织中表达呈阳性 ,阳性率为 78 3% (6 5 83) ;MMP 2表达强度与胃癌分化程度、淋巴结转移、浸润深度、浸润型生长、TNM分期显著相关 (P <0 0 5 ) ,而与肿瘤大小无关。E cadherin与MMP 2的表达调控呈负相关 ,两者的表达水平呈负相关性。结论 :E cadherin的表达下调和MMP 2表达上调与胃癌浸润和转移密切相关 ,两者在癌组织中表达的检测有助于对胃癌患者预后的判断     

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.     

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。     

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.