COX-2和VEGF-C在乳腺癌组织中的表达与预后的关系

目的:探讨COX-2和VEGF-C在乳腺癌组织的表达及两者与淋巴结转移和预后的关系.方法:收集从1999年～2006年在中国医科大学附属第一医院肿瘤外科接受根治性手术且有完整随访资料的乳腺癌患者组织蜡块共117例,构建组织芯片.应用免疫组化sP法检测COX-2和VEGF-C的表达,分析COX-2和VEGF-C在乳腺癌中表达的相关性,两者与乳腺癌临床病理因素的相关性、与预后的关系.结果:117例乳腺癌组织中与周围组织相比COX-2、VEGF-C均有表达增高,分别为55.8%、58.1%,且二者表达呈正相关(r=0.356,P＜0.001).COX-2和VEGF-C的表达与肿瘤临床分期、淋巴结转移及肿瘤有否复发呈正相关.COX-2的表达还与ER(r=0.224.P=0.015)、Her-2表达(r=0.254,P=0.006)呈正相关.所有患者手术后随访时间为4～70个月,COX-2、VEGF-C表达与无病生存期明显相关.结论:在乳腺癌组织中,COX-2、VEGF-C均呈高表达且两者呈正相关.两者的高表达与乳腺癌淋巴结转移及预后密切相关.     

乳腺癌中血管内皮生长因子和环氧合酶-2蛋白表达与临床因素的关系

 【摘要】　目的　探讨乳腺癌组织中血管内皮生长因子（VEGF）和环氧合酶-2（COX-2）蛋白表达及其与临床的相关性。方法　应用免疫组织化学EliVision法检测60例原发性乳腺浸润性导管癌组织中VEGF和COX-2蛋白表达,分析其表达与年龄、肿瘤大小、TNM分期、肿瘤病理组织学分级和腋窝淋巴结转移等临床病理因素和预后的关系。结果　乳腺癌组织中VEGF的表达与肿瘤大小、TNM分期、病理学分级和腋窝淋巴结转移密切相关（P＜0.05）,而与年龄无关。乳腺癌组织中COX-2表达与TNM分期、病理学分级和腋窝淋巴结转移密切相关,而与年龄和肿瘤大小无关。VEGF与COX-2两者表达呈正相关（r＝0.2615,P＜0.05）。在死亡组中,VEGF和COX-2蛋白表达均明显高于生存组（P＜0.05）。结论　乳腺癌中VEGF和COX-2蛋白表达上调,与乳腺癌的发生、发展、转移及浸润密切相关。VEGF与COX-2表达在乳腺癌中呈正相关,联合检测有助于筛选出具有高复发及转移危险的乳腺癌患者,判断其预后,从而指导临床治疗。     

117例乳腺癌组织中COX-2和VEGF-C表达及临床意义

目的:分析117例乳腺癌患者癌组织中环氧化酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)表达和两者的相关性,探讨其与临床病理特征,淋巴结转移及预后的关系.方法:收集117例乳腺癌患者的一般情况、临床病理特征和癌组织蜡块,构建乳腺癌组织芯片.应用免疫组化SP法检测COX-2和VEGF-C 的表达. 结果: 117 例乳腺癌组织中COX-2、VEGF-C表达分别为 55.8%、58.1%,且二者呈正相关(r=0.356,P<0.001).COX-2 和VEGF-C的表达均与临床分期、淋巴结转移及有否复发呈正相关,与肿块大小,PR,病理类型,组织学分级无关.COX-2的表达还与ER、Her-2表达呈正相关.结论:COX-2和VEGF-C在乳腺癌组织中均呈高表达且两者呈正相关,检测两者对评估乳腺癌患者的预后有一定的临床意义.     

乳腺癌组织VEGF-C表达临床意义的研究

目的:观察乳腺癌组织血管内皮生长因子-C(VEGF-C)的表达与淋巴结转移的相关性,明确VEGF-C能否作为乳腺癌淋巴结转移的标志.方法:采用免疫组织化学SP法对108例乳腺癌组织切片染色,观察VEGF-C的表达情况,评价VEGF-C的表达与淋巴结转移及其他临床病理因素的关系.结果:77例(71.3%)乳腺癌组织VEGF-C呈阳性表达,VEGF-C阳性表达与淋巴结转移有明显关系(χ2=6.245,P=0.044),同时与肿瘤大小亦有相关性,χ2=6.708,P=0.035.VEGF-C的表达与患者年龄、病理类型以及ER、PR、c-erbB-2的表达情况无明显相关.结论:VEGF-C对于乳腺癌淋巴结转移起重要作用,是乳腺癌重要的预后因子,而且与肿瘤大小呈正相关.     

Ⅱ、Ⅲ期直肠癌组织中COX-2和VEGF-C的表达及其与肿瘤血管生成及预后的关系

背景与目的:Ⅱ、Ⅲ期直肠癌术后常发生血道转移,肿瘤新生血管生成是肿瘤血道转移的重要步骤,环氧合酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)与肿瘤的新生血管生成有一定关系。本研究将探讨COX-2和VEGF-C在Ⅱ、Ⅲ期直肠癌组织中的表达及其与肿瘤生物学特征和肿瘤血管生成的关系。方法:免疫组化法检测Ⅱ、Ⅲ期直肠癌组织COX-2和VEGF-C的表达,并测定肿瘤微血管密度(MVD)。结果:①直肠癌组织中COX-2及VEGF-C高表达率均为72.5%,高于癌旁正常组织(9.8%和50.0%)(P均<0.05);直肠癌组织中MVD值为18.41±8.86,高于癌旁正常组织(11.24±7.4)(P<0.05);②COX-2在直肠癌组织中的表达与肿瘤组织的分化程度、浸润深度及VEGF-C的表达相关,与肿瘤的大小及淋巴结转移不相关;③VEGF-C在直肠癌组织中的表达仅与COX-2的表达相关,而与淋巴结转移、肿瘤组织的分化及浸润深度不相关;④在直肠癌组织中的MVD与肿瘤组织的分化程度、及VEGF-C、COX-2的表达相关,与肿瘤的大小、浸润深度及淋巴结转移不相关。结论:COX-2和VEGF-C的表达与Ⅱ、Ⅲ期直肠癌组织中肿瘤血管生成有密切关系,但与预后无关。     

乳腺癌组织COX-2和VEGF-C表达与淋巴转移的相关性研究

目的:探讨乳腺癌组织中环氧合酶-2(COX-2)表达和血管内皮生长因子-C(VEGF-C)水平与淋巴转移的相关性.方法:RT-PCR法检测54例乳腺癌组织、相应癌旁及正常组织和30例乳腺良性肿瘤组织中CoX-2 mRNA表达情况;ELISA法检测54例乳腺癌患者和30例乳腺良性肿瘤患者术前、术后及30位正常人血清中VEGF-C水平.结果:1)癌和癌旁组织中COX-2阳性表达率分别为78%(42/54)和13%(7/54),正常乳腺及良性肿瘤组织中呈弱表达(9%)或无表达;在Ⅰ、Ⅱ期和Ⅲ期乳腺癌中其阳性表达率分别为45%(17/38)和63%(10/16);在淋巴结转移阳性患者中呈高表达,表达率为82%(28/34),而在阴性者中表达率仅为30%(6/20).2)VEGF-C在乳腺癌患者术前血清中的水平(6 142.98 ng/L)明显高于乳腺良性肿瘤患者(5 268.92 ng/L),P<0.05;在有淋巴结转移的乳腺癌患者血清中的表达水平(6 369.27 ng/L)明显高于淋巴结转移阴性者(5 884.90 ng/L),P<0.05;在Ⅰ、Ⅱ期术前患者中VEGF-C水平为5 346.87 ng/L,Ⅲ期为5 962.13 ng/L.3)COX-2和VEGF-C在有淋巴结转移的乳腺癌中较无淋巴结转移者表达明显增高,两者与乳腺癌淋巴转移呈正相关,r=0.629,P=0.028.结论:COX-2和VEGF-C在乳腺癌的发生发展中起重要作用,两者共同促进乳腺癌的淋巴结转移.中华肿瘤防治杂志,2009,16(1):51-54     

实时荧光定量 PCR检测早期宫颈癌及前哨淋巴结VEGF-C及VEGF-D mRNA表达

[目的]研究血管内皮生长因子(VEGF)-C及VEGF-D mRNA在早期宫颈癌和前哨淋巴结中的表达水平.[方法]收集51例早期官颈癌患者宫颈癌组织、癌周组织、前哨转移淋巴结、非前哨无转移淋巴结、正常区域组织.透射电镜观察淋巴转移情况,实时荧光定量PCR检测VEGF-C及VEGF-D mRNA的表达量,并研究其与宫颈癌临床病理各因素之间的关系.[结果]透射电镜显示宫颈癌周区可见到淋巴管增生.VEGF-C及VEGF-D mRNA在宫颈癌内、癌周、前哨转移淋巴结中的表达均显著高于正常宫颈组织和非前哨无转移淋巴结(P＜0.05).VEGF-C及VEGF-D mRNA在宫颈癌组织中的表达在不同淋巴结转移、淋巴管侵犯、肿瘤浸润深度下差异有统计学意义(P均＜0.05),而不同年龄、临床分期、病灶大小、组织分化、病理类型之间的差异无统计学意义(P均＞0.05).[结论]VEGF-C及VEGF-D在早期宫颈癌的淋巴结转移中起重要作用,可能成为预测宫颈癌淋巴结转移的关键指标,有希望成为抑制宫颈癌淋巴结转移的治疗靶点.     

血管内皮生长因子-C mRNA和微血管密度与乳腺癌预后相关性关系的探讨

目的:探讨乳腺癌组织内血管内皮生长因子-C mRNA(VEGF-C mRNA)的表达及微血管密度(MVD),分析MVD和VEGF-CmRNA表达与乳腺癌患者预后的意义.方法:采用原位杂交技术观察92例乳腺浸润性导管癌(IDC)组织中VEGF-C mRNA的表达;CD105(细胞膜糖蛋白)标记乳腺癌组织中微血管并观察MVD.结果:不同组织学分级乳腺IDC组织中VEGF-C mRNA表达差异有统计学意义,P<0.05;在淋巴结转移组VEGF-CmRNA表达明显高于淋巴结未转移组,P<0.01;VEGF-C mRNA表达阳性组MVD明显高于VEGF-C mRNA表达阴性组,P<0.001;淋巴结转移组乳腺癌组织中MVD高于淋巴结未转移组,差异有统计学意义(P<0.001),VEGF-C mRNA表达阳性组(高MVD组)较VEGF-C mRNA表达阴性组(低MVD组)5年生存率低,差异有统计学意义,P<0.05.结论:VEGF-C mRNA表达与乳腺癌淋巴结转移及MVD密切相关,检测乳腺癌组织中VEGF-C mRNA表达及观察MVD可能预测乳腺癌预后.     

乳腺癌患者血清与肿瘤组织基质细胞衍化因子表达及其临床意义的研究

目的:探讨基质细胞衍化因子(stromal cell-derived factor-1, SDF-1)在乳腺癌患者的血浆、肿瘤组织及淋巴结中表达水平与乳腺癌及淋巴结转移状况之间的关系.方法:应用酶联免疫吸附试验(ELISA)检测患者血浆中的SDF-1蛋白水平;应用逆转录-聚合酶链反应(RT-PCR)半定量检测乳腺正常组织、良性肿瘤组织及乳腺癌组织中SDF-1 mRNA水平;应用免疫组化法(IHC)检测乳腺正常组织、良性和恶性肿瘤组织及淋巴结中SDF-1蛋白的表达水平及分布情况.结果:良性肿瘤与恶性肿瘤患者血浆中SDF-1蛋白表达为(9.98±10.38)和(56.21±10.37)pg/mL,P<0.01.乳腺癌组织SDF-1 mRNA表达水平为0.596±0.257,较正常组织(0.291±0.032)和良性肿瘤组织(0.32±0.071)显著增加.乳腺癌组织中,有淋巴结转移者的SDF-1 mRNA的表达水平(0.729±0.265)较无淋巴结转移者(0.419±0.104)有显著增加,P=0.034.IHC法显示SDF-1蛋白在正常组织和良性肿瘤组织中呈现低水平表达,在乳腺癌组织中呈现高水平表达.有癌细胞转移的淋巴结其SDF-1蛋白水平表达较无癌细胞转移的淋巴结有增加,P=0.015.结论:临床有望通过检测易于获得的血浆标本SDF-1蛋白水平预测淋巴结转移状况.     

VEGF-C,VEGF-D在乳腺癌中的表达及其与淋巴结转移及预后的关系

目的探讨VEGF-C和VEGF-D在乳腺癌组织中的表达以及与淋巴结转移、预后的相关性。方法采用SP免疫组化法检测78例乳腺癌癌组织和30例癌旁组织中VEGF-C,VEGF-D的表达水平,并完成所有患者的5年的随访资料。结果 78例乳腺癌癌组织中VEGF-C/D表达与癌旁组织相比差异有统计学意义(P<0.05);乳腺癌中VEGF-C表达与VEGF-D表达无相关性。VEGF-C,VEGF-D的表达水平与乳腺癌脉管内侵犯、淋巴结转移密切相关(P<0.05),但与年龄、肿瘤大小、TNM临床分期、ER、PR及Her-2的表达无关(P>0.05)。VEGF-C和VEGF-D的表达水平与乳腺癌的总生存期及无病生存期密切相关(P<0.05)。结论 VEGF-C,VEGF-D在乳腺癌组织中呈高表达;VEGF-C/D的表达水平与乳腺癌淋巴结转移能力和预后密切相关。     

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.     

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。     

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.     

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.