血管内皮生长因子在大肠癌中的表达及预后价值

目的：研究血管内皮生长因子（ＶＥＧＦ）在朋肠癌中的表达及其与临床病理特征的关系。方法：采用免疫组织化学方法检测８０例大肠癌手术标本肿瘤组织内的血管内皮生长因子（ＶＥＧＦ）和微血管计数（ＭＶＤ）。结果：ＶＥＧＦ表达阳性率为６１．２％,ＶＥＧＦＤ表达阳性的肿瘤组织其ＭＶＤ明显高于阴性者（Ｐ＜０．０５）。ＶＥＧＦ表达与肿瘤的浸润性生长、浆膜浸润、淋巴结转移和肝转移有明显相关性（Ｐ＜０．０５）。此外,ＶＥ     

大肠癌组织血管内皮生长因子表达与血管生成及细胞增殖的关系

血管生成是恶性肿瘤生长和转移的关键步骤，肿瘤内微血管密度（ intratumoral microvescular density， MVD）是影响肿瘤预后的重要因素，肿瘤血管生成过程受多种血管生成因子的调节，其中血管内皮生长因子（ vascular endothelial growth factor,VEGF）在血管生成过程中最为重要。本研究采用免疫组织化学方法，对病理确诊的 98例大肠癌组织进行 VEGF表达的检测，同时检测 MVD和增殖细胞核抗原（ proliferating cell nuclear antigen， PCNA），并探讨其与肿瘤血管生成及瘤细胞增殖的关系。     

肝门部胆管癌组织中VEGF和血管生成相关性的研究

目的：探讨肝门部胆管癌组织中血管内皮细胞生长因子（ＶＥＧＦ）和血管生成的相关性。方法：应用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）和免疫组化技术对２６例肝门部胆管癌、癌周组织及１２例正常组织中ＶＥＧＦｍＲＮＡ和蛋白及微血管密度（ＭＶＤ）进行了检测。结果：２６例肝门部胆管癌组织中ＶＥＧＦｍＲＮＡ阳性表达率为７６．９％（２０／２６）;癌周组织阳性表达率为２８．９％（７／２６）;正常组织表达率为８．３％（１／１２）,三者差异有显著性（Ｐ＜０．０１）。ＶＥＧＦｍＲＮＡ阳性表达与ＶＥＧＦ蛋白表达具有一致性;ＶＥＧＦｍＲＮＡ阳性者ＭＶＤ值显著高于阴性者（Ｐ＜０．０１）;ＶＥＧＦｍＲＮＡ表达和ＭＶＤ与肝门部胆管癌的分化程度、浸润转移密切相关（Ｐ＜０．０５）;而与发生部位、病理类型、肿瘤大小、临床分型无关（Ｐ＞０．０５）。结论：ＶＥＧＦ在肝门部胆管癌发生和浸润转移过程中发挥重要作用,肿瘤血管生成与肝门部胆管癌浸润转移密切相关。     

大肠癌组织中Ｎｅｕｒｏｐｉｌｉｎ-１的表达及其与肿瘤血管生成的相关性研究

目的：检测大肠癌组织中神经纤毛蛋白-１（Ｎｅｕｒｏｐｉｌｉｎ-１,ＮＲＰ-１）ｍＲＮＡ的表达情况及微血管密度（ＭＶＤ）值,探讨ＮＲＰ-１ｍＲＮＡ的表达与ＭＶＤ间的相关性,以期了解ＮＲＰ-１与肿瘤血管生成的关系。方法：取４５例大肠癌组织及相应正常大肠组织,采用半定量ＲＴ-ＰＣＲ方法检测其ＮＲＰ-１ｍＲＮＡ的表达情况,采用免疫组化染色法检测ＣＤ１０５标记的新生肿瘤血管,计数ＭＶＤ值。结果：４５例大肠癌组织中３９例可见ＮＲＰ-１ｍＲＮＡ的表达,阳性率为８７.０％;相应正常大肠组织仅３例表达,阳性率为６.７％。大肠癌组织中ＮＲＰ-１ｍＲＮＡ的表达程度与肿瘤的大小、浸润的深度、淋巴结转移呈正相关（Ｐ＜０.０５）,与肿瘤部位、组织学类型、分化程度、患者的性别及年龄无关（Ｐ＞０.０５）。大肠癌组织中ＮＲＰ-１ｍＲＮＡ的表达程度随ＭＶＤ值的增加而升高（ｒ＝０.３８,Ｐ＝０.０１）。结论：ＮＲＰ-１可能与大肠癌的肿瘤血管生成相关,ＮＲＰ-１ｍＲＮＡ高表达代表着大肠癌不良的生物学行为趋向。     

基质金属蛋白酶-9在大肠癌中的表达及其与血管生成的相关性

[目的]探讨基质金属蛋白酶-9（MMP-9）在大肠癌中的表达及其与血管生成关系的临床意义。[方法]应用免疫组化SP法检测108例大肠癌组织中MMP-9、血管内皮生长因子（VEGF）的表达以及微血管密度（MVD）。[结果]MMP-9、VEGF的表达和MVD值与肿瘤分化、淋巴结转移、Dukes分期明显相关；MMP-9、VEGF阳性表达组的MVD值显著高于阴性组；MMP-9与VEGF在大肠癌组织中表达呈正相关。[结论]MMP-9与大肠癌血管生成有关，检测MMP-9的表达可作为反映大肠癌侵袭和转移的生物学指标。     

促血管生成素在大肠癌组织的表达及其临床病理意义

目的　观察促血管生成素（Ａｎｇ）-１、Ａｎｇ-２及其受体Ｔｉｅ-２在大肠癌中的表达,探讨其与大肠癌血管生成的关系及临床病理意义。方法　采用免疫组化ＰＶ-９０００二步法观察５０例大肠癌和１０例正常大肠黏膜组织中Ａｎｇ-１、Ａｎｇ-２、Ｔｉｅ-２的表达,采用ＣＤ１０５标记检测微血管密度（ＭＶＤ）。结果　大肠癌组织Ａｎｇ-１的表达低于正常大肠黏膜,Ａｎｇ-２、Ｔｉｅ-２的表达高于正常大肠黏膜,差异均有统计学意义（Ｐ＜０.０５）;Ａｎｇ-１、Ａｎｇ-２的表达在不同分化程度间差异有统计学意义（Ｐ＜０.０１）;Ａｎｇ-１在淋巴结转移组的表达低于无转移组（Ｐ＜０.０５）;Ａｎｇ-２在淋巴结转移组高于无转移组（Ｐ＜０.０５）,在Ｄｕｋｅｓ'Ｃ、Ｄ期明显高于Ｄｕｋｅｓ'Ａ、Ｂ期（Ｐ＜０.０１）;Ｔｉｅ-２在淋巴结转移组的表达高于无转移组（Ｐ＜０.０５）;Ａｎｇ-２、Ｔｉｅ-２的表达与ＭＶＤ均呈正相关（ｒ＝０.３４５,Ｐ＜０.０５;ｒ＝０.２９９,Ｐ＜０.０５）。结论　促血管生成素与大肠癌的病理分化程度、Ｄｕｋｅｓ分期、淋巴结转移有关,并且在大肠癌血管生成过程中发挥重要作用。     

胃癌组织中Ａｎｇ ２和ＶＥＧＦ的表达与血管生成的关系

目的：研究胃癌组织中血管生成素-２（Ａｎｇ-２）和血管内皮生长因子（ＶＥＧＦ）的表达与临床病理学特征和肿瘤血管生成的关系。方法：应用免疫组织化学方法检测５５例胃癌组织以及１２例胃癌癌旁组织和正常胃组织中Ａｎｇ-２、ＶＥＧＦ表达及微血管密度（ＭＶＤ）。结果：Ａｎｇ-２、ＶＥＧＦ表达及ＭＶＤ在胃癌组织中均显著高于癌旁组织及正常胃组织（Ｐ＜０.０５）;胃癌组织Ａｎｇ-２、ＶＥＧＦ表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关（Ｐ＜０.０５）;Ａｎｇ-２与ＶＥＧＦ表达呈正相关性（Ｐ＜０.０５）。结论：Ａｎｇ-２、ＶＥＧＦ在胃癌组织中高表达,两者在胃癌的肿瘤血管生成和进展中起重要作用。     

血管生成与DMBA诱发的大鼠乳腺癌转移的关系

目的：探讨肿瘤血管生成与乳腺癌转移的关系。方法：采用二甲基苯蒽（ＤＭＢＡ）诱发的大鼠乳腺癌模型,以免疫组织化学染色方法检测肿瘤组织微血管密度（ＭＶＤ）及血管内皮生长因子（ＶＥＧＦ）表达。结果：转移组原发瘤灶ＭＶＤ及瘤细胞ＶＥＧＦ表达显著的高于非转移组（分别Ｐ〈０．００１和Ｐ,０．０２）及良性肿瘤组（两者均Ｐ〈０．００１）。结论：ＶＥＧＦ介导的血管生民在促进乳腺癌转移的过程中可能起重要作用。     

大肠癌活化白细胞黏附分子的表达及其与肿瘤细胞增殖和血管生成的关系

目的探讨活化白细胞黏附分子（ALCAM）在大肠癌中的表达及其与大肠癌血管生成、细胞增殖的关系。方法运用流式细胞术直接免疫荧光法检测66例原发性大肠癌肿瘤组织及相应癌旁大肠黏膜组织ALCAM的表达量。ALCAM蛋白表达量以阳性率和平均荧光强度（MFI）表示。运用免疫组织化学法检测肿瘤组织CD34、增殖细胞核抗原（PCNA）的表达情况，根据CD34的染色情况计算大肠癌组织的微血管密度（MVD），根据PCNA染色情况计算肿瘤细胞PCNA标记指数。结果大肠癌肿瘤组织ALCAM阳性率48．20±20．68，明显高于癌旁黏膜组织10．58±2．03。肿瘤组织MFI10．05±4．47，明显高于癌旁黏膜4．56±2．10（t=9．832，P〈0．001）。ALCAM的表达增强与大肠癌的Dukes分期、pTNM分期、淋巴结转移呈正相关。随着ALCAM表达增强，细胞增殖指数也随之升高（P〈0．05）。大肠腺癌ALCAM蛋白MFI与MVD呈正相关（r=0．267，P〈0．05）。而ALCAM蛋白肿瘤细胞阳性表达率与MVD未见明显相关（r=0．234，P=0．059）。结论ALCAM在大肠腺癌中表达水平明显上调，并与肿瘤细胞增殖、血管生成密切相关，提示ALCAM可能在大肠癌发生发展中起重要作用。     

大肠癌微血管密度和血管内皮生长因子表达的研究

目的 探讨大肠癌间质微血管密度（ＭＶＤ）和血管内皮生长因子（ＶＥＧＦ）表达与肿瘤浸润和转移和关系。方法 应用ＣＤ３４抗体和ＶＥＧＦ抗体,采用免疫组化Ｓ－Ｐ法对５６例手术切除的大肠癌患者进行血管标记和染色,并取１０例正常组织对照。结果 有淋巴结转移组大肠癌ＭＶＤ、ＶＥＧＦ表达强度与无淋巴结转移组、正常对照组组间比较,均有显著性差异（Ｐ〈０．０１）,且ＭＶＤ与ＶＥＧＦ表达两者呈相关（ｒ＝０．９２）。结     

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.     

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.