子宫内膜癌手术预后因素的多因素分析

目的:分析和评价子宫内膜癌常用临床病理因素(绝经前后、手术病理分期、组织学分级、淋巴结转移、病理类型、术后辅助治疗、肌层浸润深度)和生物学因素(COX-2、VEGF、KDR及ER、PR)对子宫内膜癌手术预后的影响,筛选出对子宫内膜癌手术预后最有显著的影响因素.方法:将可能与子宫内膜癌预后有关的常用临床病理因素和生物学因素进行单因素分析.通过Cox模型对单因素分析筛选出的影响子宫内膜癌预后的因素进行多因素分析.结果:137例子宫内膜癌患者中,通过随访,共获得确切随访者112例,5年生存率为83.04%.Ⅰ～Ⅳ期5年生存率分别为89.66%,80.00%,53.85%,0.子宫内膜癌组织中COX-2、VEGF及KDR蛋白的阳性率分别为47.32%、66.07%及52.68%,且三者表达具有协同性.COX-2、VEGF、KDR蛋白阳性患者5年累积生存率分别为75.47%、78.38%、72.88%.将这些临床病理因素及生物学因素进行单因素分析,结果手术病理分期、组织学分级、肌层浸润深度、有无淋巴结转移、COX-2阳性表达、KDR阳性表达、ER阳性表达、PR阳性表达8个因素与预后明显相关(P 均＞＜0.05＝,绝经前后、病理类型、术后辅助治疗、VEGF阳性表达与预后无关(P 均＞0.05).应用Cox模型对单因素分析筛选出的8个有显著意义的因素进行多因素分析表明:肌层浸润深度、手术病理分期、组织学分级是影响子宫内膜癌手术预后最显著的3个因素.结论:肌层浸润深度、手术病理分期、组织学分级是影响子宫内膜癌手术预后的因素,但浸润肌层是影响子宫内膜癌手术预后的最重要的因素.     

COX-2、VEGF、Ki67在子宫内膜癌中的表达及意义

目的探讨环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)和增殖细胞核相关抗原(Ki67)在子宫内膜癌发生、发展中的作用。方法采用免疫组织化学Envision法检测50例子宫内膜癌和15例正常子宫内膜组织中COX-2、VEGF、Ki67的表达。结果子宫内膜癌组织中COX-2、VEGF、Ki67的表达明显高于正常子宫内膜组织(P<0.01);COX-2的高表达与临床分期无关(P>0.05),与分化程度和浸润深度有关(P<0.01);VEGF的高表达与临床分期、浸润深度无关(P>0.05),分化程度有关(P<0.05);Ki67的高表达与临床分期(P<0.05)、分化程度、浸润深度有关(P<0.01)。COX-2与VEGF和Ki67的表达间存在正相关(r=0.39,P<0.01;r=0.32,P<0.05)。结论COX-2、VEGF、Ki67与子宫内膜癌的发生和发展相关,COX-2可通过使VEGF高表达,增加细胞增殖活性促进子宫内膜癌的发生、发展。     

FAP-1和Fas在子宫内膜癌中的表达及其临床意义

目的:研究Fas相关磷酸酯酶-1(FAP-1)和Fas在子宫内膜癌中的表达及其与临床病理特征间的关系.方法:采用S-P免疫组化法检测63例子宫内膜癌中:FAP-1、Fas的表达,同时检测13例子宫内膜非典型增生及20例正常子宫内膜组织作为对照.结果:FAP-1在子宫内膜癌中表达率为71.4%,明显高于正常子宫内膜中的表达率25%(P<0.05).Fas在子宫内膜癌和正常子宫内膜组织中表达率分别为52.4%和85%(P<0.05).Fas蛋白表达阳性、阴性的子宫内膜癌组织中,FAP-1表达阳性率分别为51.5%、93.3%,两者间呈明显负相关(P<0.05).FAP-1的阳性表达与子宫内膜癌临床分期、组织分级有关(P<0.05),与年龄、肌层浸润及淋巴结转移无关(P>0.05);Fas的阳性表达与子宫内膜癌组织分级、淋巴结转移有关(P<0.05),与年龄、临床分期及肌层浸润无关(P>0.05).结论:FAP-1抵抗Fas介导的细胞凋亡在子宫内膜癌的发生、发展中起一定作用,FAP-1与Fas可作为判断子宫内膜癌生物学行为的参考指标,为子宫内膜癌的基因治疗提供参考依据.     

乙酰肝素酶蛋白与子宫内膜癌临床病理特征的关系研究

目的：研究乙酰肝素酶（heparanase,Hpa）在子宫内膜癌中的表达,并探讨其临床意义.方法：采用免疫组织化学SP法检测48例子宫内膜癌组织中Hpa蛋白的表达情况.结果：Hpa蛋白在子宫内膜癌中阳性率显著高于正常子宫内膜、子宫内膜增生症（P＞0.05）.单因素分析表明浸润不超过内1/2肌层者的Hpa蛋白阳性率显著低于浸润达到外1/2肌层者（P＞0.05）.有淋巴转移组的Hpa蛋白阳性率显著高于无淋巴转移组（P＞0.05）.Ⅰ-Ⅱ期组的Hpa蛋白阳性率显著低于Ⅲ-Ⅳ期组（P＞0.05）.弥漫型内膜癌中Hpa蛋白阳性率高于局限性（P＞0.05）.中、低分化内膜癌中Hpa表达与细胞分化无关（P＞0.05）.多因素Logistic回归分析结果表明Hpa蛋白表达只与淋巴转移、临床分级及肌层浸润显著相关（P＜0.05）.结论：Hpa在子宫内膜癌的阳性率显著高于正常子宫内膜、子宫内膜增生症.Hpa表达与转移、临床分期显著相关.     

实时定量PCR检测VEGF在子宫内膜癌及外周血中的表达及其临床意义

目的:检测血管内皮生长因子(vascular endothelial growth factor,VEGF)基因在子宫内膜癌、癌周组织、正常子宫内膜及外周血循环中的表达情况,分析其在肿瘤生长、转移中的作用.方法:采用荧光实时定量PCR方法检测51例子宫内膜癌患者的癌组织和癌周组织、40例正常子宫内膜组织及其对应的患者外周血中的VEGF表达情况,分析其与临床病理参数之间的关系.结果:子宫内膜癌组织中VEGF表达水平显著高于癌周组织及正常子宫内膜组织(P<0.05) ;与临床分期、组织学分级、淋巴结转移、肌层浸润深度密切相关 (均P<0.05),但与肿瘤病理类型及患者是否绝经无明显相关性(P>0.05).子宫内膜癌患者外周血中VEGF的表达明显高于正常对照(P>0.05),且与临床分期、组织学分级、病理类型及淋巴结转移有显著相关(均P<0.05),但与肌层浸润程度及患者是否绝经无明显相关性.结论:荧光实时定量PCR可以敏感、特异性地检测子宫内膜癌组织及外周血中VEGF的表达,VEGF在子宫内膜癌的发生、侵袭、转移过程中可能起重要作用.     

子宫内膜癌组织中Bim蛋白表达及其临床意义

目的:探讨促凋亡基因Bim在子宫内膜癌发生与发展中的作用.方法:应用免疫组化SP方法检测11例正常增殖期子宫内膜、13例非典型增生子宫内膜及55例子宫内膜癌Bim蛋白的表达.结果:在子宫内膜癌组织Bim表达阳性率为47.2%,明显低于正常增殖期内膜组织(100%)及非典型增生内膜组织(76.9%),三者之间比较有显著差异(x2=7.944,P＜0.05).而在子宫内膜癌各组织分级、临床分期及肌层浸润程度之间,Bim蛋白表达阳性率均无明显差异(P＞0.05).结论:Bim蛋白表达改变与子宫内膜癌的发生密切相关.     

PTEN蛋白表达与子宫内膜癌的相关性研究

目的:探讨子宫内膜癌中抑癌基因PTEN的表达,及其与子宫内膜癌临床病理特征及预后的关系.方法:采用免疫组化检测16例正常子宫内膜、32例子宫内膜癌组织中PTEN蛋白的表达,分析其与临床病理的相关性.结果:抑癌基因PTEN在子宫内膜癌组中蛋白阳性表达显著低于正常子宫内膜组(P<0.01).PTEN阳性表达的缺失与组织学分级与肌层浸润深度有关(P<0.05).结论:PTEN基因突变及蛋白表达缺失与子宫内膜癌的发生有关,与子宫内膜癌的分化程度、肌层浸润深度有相关性.     

子宫内膜癌组织PTEN和c-erbB-2蛋白表达临床意义的探讨

-2的阳性表达率明显高于正常子宫内膜和子宫内膜不典型增生,P<0.05; c-erbB-2阳性表达与子宫内膜癌的病理分级、临床分期、肌层浸润深度和淋巴转移相关(P<0.05),但与不典型增生的程度无关(P>0.05).在子宫内膜癌组织中PTEN的表达缺失率与c-erbB-2的过度表达呈正相关.结论:PTEN蛋白的表达缺失与子宫内膜癌的发生有关;c-erbB-2蛋白的高表达提示预后不良;PTEN和c-erbB-2联合检测可作为筛选复发转移高危因素的标志.     

子宫内膜癌中PTEN蛋白、P-AKT蛋白的表达及意义

目的:检测子宫内膜癌组织中PTEN蛋白及P-AKT蛋白表达并探讨其意义.方法:采用免疫组织化学法检测66例子宫内膜癌、28例正常子宫内膜组织中PTEN蛋白及P-AKT的表达.结果:子宫内膜癌组织中PTEN蛋白为缺失表达,高于正常子宫内膜组织(P＜0.05),而且PTEN表达在G1级肿瘤高于G2、G3级(P＜0.05),PTEN蛋白缺失率与肿瘤组织类型有关(P＜0.05),与肌层浸润、淋巴结转移及病理分期无明显关系(P＞0.05).子宫内膜癌组织中P-AKT蛋白表达为高表达,P-AKT的表达与肿瘤组织学分级、病理学分期、有无淋巴结转移以及肿瘤浸润子宫肌层深度显著相关(P＜0.05),其表达与组织学类型无关(P＞0.05).P-AKT与PTEN的表达呈明显负相关.结论:PTEN表达缺失与临床病理参数无关,蛋白表达缺失常发生细胞分化较差的子宫内膜癌.PTEN蛋白表达缺失与P-AKT表达水平有关.     

子宫内膜癌组织HIF-1α和VEGF及其受体表达与微血管密度相关性的探讨

目的:研究HIF-1α、VEGF及其受体KDR和微血管密度(MVD)在子宫内膜癌组织中的表达及相互关系.方法:采用免疫组化法检测HIF-1α、VEGF、KDR在39例子宫内膜癌、18例子宫内膜不典型增生及17例正常子宫内膜组织中的表达状况,应用CD34标记MVD.结果:HIF-1α、VEGF、KDR、MVD在子宫内膜癌组织中呈高表达,显著高于子宫内膜不典型增生组织及正常子宫内膜组织,P值均<0.05,在子宫内膜癌组织中HIF-1α、VEGF、KDR的阳性表达率随肿瘤手术-病理分期期别的升高而增高,其中I期与Ⅱ～Ⅳ期比较差异有统计学意义,P=0.014 9.结论:HIF-1α、VEGF、KDR和MVD在正常子宫内膜、子宫内膜不典型增生及子宫内膜癌组织中的表达依次增高,提示HIF-1α、VEGF、KDR和MVD在子宫内膜癌发生发展中有重要作用,可将它们视为子宫内膜癌潜在侵袭性的肿瘤标志.     

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.