Survivin、Caspase-3、突变型p53在膀胱癌中的表达及预后意义

目的:Survivin、Caspase-3、突变型p53在膀胱癌中的表达及预后意义。方法:应用S-P免疫组织化学法检测55例行TUR-BT术切除膀胱癌标本组织石蜡切片中Survivin、Caspase-3、突变型p53表达的情况,结合临床资料进行分析,15例正常膀胱黏膜为对照。结果:Survivin在膀胱癌标本中表达阳性率为70.9%(39/55),而正常对照组中无一例阳性表达;Caspase-3在膀胱癌标本中表达阳性率为36.4%(20/55),与对照组阳性率80%(12/15)相比差异有统计学意义(P<0.05)。突变型p53在膀胱癌标本中表达阳性率为55.5%(36/55),与对照组阳性率33.3%(5/15)相比差异无统计学意义(P>0.05),它与肿瘤数目、膀胱癌的初发和复发、病理分级显著相关(P<0.05)。Survivin表达与膀胱癌的初发和复发、病理分级、临床分期有显著相关(P<0.05),但与肿瘤数目无关;膀胱癌中Survivin和Caspase-3表达,Caspase-3和突变型p53相比差异有统计学意义(P<0.05)。结论:Survivin在膀胱癌中高表达提示该基因在膀胱癌发生发展中有着重要的作用,Caspase-3表达和突变型p53对临床医生判断膀胱癌的预后有着重要的指导意义。     

Survivin、Caspase-3、突变型p53在膀胱癌中的表达及预后意义

目的：Survivin、Caspase-3、突变型p53在膀胱癌中的表达及预后意义。方法：应用S-P免疫组织化学法检测55例行TUR-BT术切除膀胱癌标本组织石蜡切片中Survivin、Caspase-3、突变型p53表达的情况,结合临床资料进行分析,15例正常膀胱黏膜为对照。结果：Survivin在膀胱癌标本中表达阳性率为70.9%（39/55）,而正常对照组中无一例阳性表达;Caspase-3在膀胱癌标本中表达阳性率为36.4%（20/55）,与对照组阳性率80%（12/15）相比差异有统计学意义（P〈0.05）。突变型p53在膀胱癌标本中表达阳性率为55.5%（36/55）,与对照组阳性率33.3%（5/15）相比差异无统计学意义（P〉0.05）,它与肿瘤数目、膀胱癌的初发和复发、病理分级显著相关（P〈0.05）。Survivin表达与膀胱癌的初发和复发、病理分级、临床分期有显著相关（P〈0.05）,但与肿瘤数目无关;膀胱癌中Survivin和Caspase-3表达,Caspase-3和突变型p53相比差异有统计学意义（P〈0.05）。结论：Survivin在膀胱癌中高表达提示该基因在膀胱癌发生发展中有着重要的作用,Caspase-3表达和突变型p53对临床医生判断膀胱癌的预后有着重要的指导意义。     

Survivin、Caspase-3在膀胱癌中的表达及预后意义

目的:研究Survivin、Caspase-3在膀胱癌中的表达及预后意义。方法:应用S-P免疫组织化学法检测55例行TUR-BT术切除膀胱癌标本组织石蜡切片中Survivin、Caspase-3表达,结合临床资料进行分析,15例正常膀胱黏膜为对照。结果:Survivin在膀胱癌标本中的表达阳性率为70.9%(39/55),而正常对照组中无一例呈阳性表达。Caspase-3在膀胱癌标本中表达阳性率为36.4%(20/55),与对照组阳性率80%(12/15)相比差异有统计学关联(P<0.05)。它与肿瘤数目、膀胱癌的初发和复发、病理分级无统计学意义(P>0.05)。Survivin表达与膀胱癌的初发和复发、病理分级、临床分期有显著统计学意义(P<0.05),但与肿瘤数目无关。膀胱癌中Survivin和Caspase-3表达相比差异有统计学意义(P<0.05)。结论:Survivin在膀胱癌中高表达提示该基因在膀胱癌发生发展中有着重要的作用,Survivin和Caspase-3的表达对临床医生判断膀胱癌的预后有着重要的指导意义。     

survivin在膀胱移行细胞癌组织中的表达及与Caspase-3、p53相关性的研究

目的:研究凋亡抑制基因survivin蛋白在膀胱移行细胞癌(BTCC)中的表达及与Caspase-3、p53表达的相关性.方法:应用SP免疫组织化学法检测50例BTCC及10例正常膀胱黏膜组织石蜡切片中survivin蛋白与Caspase-3蛋白、p53蛋白表达,结合临床资料进行分析.结果:survivin在BTCC标本中阳性表达率为76.0%(38/50),在正常组织中不表达,与BTCC的组织学分级、预后显著相关(均P<0.05),但与临床病理分期无关(P>0.05);p53阳性表达率为68.0%(34/50),与对照组阳性表达率30%(3/10)相比有统计学意义(P<0.05);Caspase-3阳性表达率为36.0%(18/50),与对照组阳性率90%(9/10)相比差异有统计学意义(P<0.05).survivin与Caspase-3表达呈显著负性相关(r=-0.457,P<0.05),survivin与p53表达呈显著正性相关(r=0.317,P<0.05).结论:survivin在BTCC中高表达提示该基因在BTCC发生发展中有着重要的作用,Caspase-3失表达、p53突变与survivin阳性表达可能在BTCC的形成过程中起协同作用,对于判断BTCC预后有重要指导意义.     

凋亡相关蛋白Survivin及突变型p53在膀胱移行细胞癌中的临床意义

目的：Survivin、突变型p53在膀胱移行细胞癌（BTCC）中表达的临床意义。方法：应用SP免疫组织化学法检测60例行TUR—BT术切除BTCC标本组织石蜡切片中Survivin,突变型p53表达,结合临床资料进行分析,20例正常膀胱黏膜为对照。结果：Survivin在BTCC标本中的表达阳性率为70．0％（42／60）,而正常对照组中无1例呈阳性表达;Survivin表达与BTCC的初发、复发、病理分级有显著相关（P〈0．05）,但与肿瘤数目,临床分期无关（P〉0．05）;突变型p53在BTCC标本中表达阳性率为65．0％（39／60）,与对照组阳性率35．0％（7／20）相比差异有统计学意义（P〈0．05）,与BTCC的初发、复发、病理分级,临床分期有显著相关（P〈0．05）,它与肿瘤数目无统计学意义（P〉0．05）,BTCC中Survivin和突变型p53相比差异无统计学意义（P〉0．05）。结论：Survivin在膀胱移形细胞癌中高表达提示该基因在BTCC发生发展中有着重要的作用,Sur—vivin和突变型p53对临床医生判断BTCC的预后有着一定的临床指导意义。     

胶质瘤中p14ARF甲基化分析及其与p53表达的相关性研究

目的:探讨p14ARF甲基化与胶质瘤发生和预后的关系,及其与突变型p53 (mutant type p53,mtp53)蛋白表达的相关性.方法:采用甲基化特异性PCR(methylation specific polymerase chain reaction, MSP)法检测33例胶质瘤和12例正常脑组织中p14ARF的甲基化状况.免疫组织化学法检测58例胶质瘤和12例正常脑组织中p14ARF和mtp53蛋白的表达.结果: 胶质瘤与正常脑组织中p14ARF甲基化率分别为39.4%(13/33)和0(0/12),2组间差异有统计学意义(P<0.01).低级别组胶质瘤甲基化率(6/15)与高级别组(7/18)间差异无统计学意义(P>0.05).p14ARF甲基化情况与患者预后无明显相关性.mtp53蛋白在胶质瘤和正常脑组织中的阳性率分别为56.9%(33/58)和8.3% (1/12),2组间比较,差异有统计学意义(P<0.01),其表达在肿瘤高级别组中明显高于低级别组(P<0.05).胶质瘤中mtp53蛋白表达与p14ARF甲基化呈负相关(P<0.05).结论:p14ARF甲基化与胶质瘤发生密切相关,为胶质瘤发生的早期事件,检测p14ARF甲基化情况可作为胶质瘤早期诊断的分子生物学指标.     

术前化疗对小细胞肺癌p53及p21表达影响及意义

目的研究手术切除术前化疗与未化疗小细胞未分化肺癌p53及p21蛋白的表达,并探讨其意义.方法选择1990～1998年随访资料完整根治术后术前化疗标本33例,未化疗标本41例,石蜡切片SP染色.结果p53蛋白表达总阳性率为60.5%,p21蛋白表达总阳性率为67.4%.术前未化疗与化疗患者p53蛋白表达阳性率分别为81.8%(34/41)和38.1%(13/33),两者差异有显著性(P＜0.05);p21蛋白表达阳性率分别为81.8%(34/41)和52.4%(17/33),两者差异有显著性(P＜0.05).术前未化疗患者与化疗患者生存期差异有显著性(P＜0.05),且术前化疗患者生存期较术前未化疗患者生存期长.结论对小细胞未分化肺癌行术前化疗能降低p53及p21蛋白表达阳性率;对小细胞未分化肺癌行术前化疗延长患者生存期.     

乳腺癌分子生物学特性检测的临床意义

目的探讨乳腺癌细胞增殖活性、bcl2和突变型p53蛋白表达水平的临床意义。方法应用流式细胞术检测121例乳腺癌的DNA倍体、S期细胞百分比(SPF)及bcl2和突变型p53表达阳性率,结合雌激素受体测定和66例乳腺浸润性导管癌的组织学分级进行统计学分析。结果66例乳腺浸润性导管癌组织Ⅰ、Ⅱ、Ⅲ级间异倍体阳性率、DNA指数(DI)差异均有统计学意义(P均<0.01)。乳腺癌组织Ⅰ、Ⅱ、Ⅲ级的SPF分别为(1.84±1.02)%、(2.44±1.07)%和(2.71±1.16)%,差异有统计学意义(P<0.05);突变型p53表达阳性率分别为(1.03±1.11)%、(2.91±1.61)%和(3.37±2.13)%,差异有统计学意义(P<0.05);bcl2阳性表达率差异无统计学意义(P>0.05),但癌组织与正常组织间差异有统计学意义。雌激素受体阳性与阴性两组间,SPF分别为(2.17±1.04)%和(4.56±1.77)%,突变型p53蛋白表达阳性率分别为(2.93±1.63)%和(4.39±2.73)%,差异均有统计学意义(P<0.05),而bcl2表达阳性率差异无统计学意义(P>0.05)。DI、SPF和p53表达阳性率两两相关,DI与SPF、DI与p53表达阳性率、SPF与p53表达阳性率的相关系数分别为0.73,0.40和0.42(P均<0.01);bcl2表达阳性率与各指标之间无相关关系。结论突变型p53和bcl2与乳腺癌的发生有一定关系;异倍体率、DI与突变型p53表达阳性率可以提示肿瘤预后;流式细胞术检测可以作为病理诊断的补充;乳腺癌患者可术前通过流式细胞术检测提示预后,确立治疗模式。     

四种基因在单发和多发性膀胱癌组织中的表达及意义

目的探讨p16、p21、p53和上皮细胞膜抗原(EMA)在单发性和多发性膀胱癌组织中的表达及意义。方法收集临床正常、单发和多发性膀胱癌标本,通过免疫组化法检测膀胱癌组织中相关基因的蛋白表达和定位分布。结果与正常膀胱黏膜上皮相比,p16和p53蛋白定位于细胞核,随着膀胱癌恶性程度的升高和侵袭程度的增加,p16蛋白表达明显下降,而p53表达明显升高(P<0.05)。p21蛋白定位于细胞膜,高分化膀胱癌的p21蛋白表达低于低分化膀胱癌(P<0.05);多发性膀胱癌表达阳性率明显高于单发性(P<0.05)。EMA主要表达于细胞浆,随着肿瘤分级和(或)分期的增加,阳性细胞数逐渐减少(P<0.05),在单发和多发性膀胱癌中的表达差异有统计学意义(P<0.05)。结论 p16、p53、p21和EMA在膀胱癌组织中不同水平的表达与膀胱癌的分级/分期密切相关,对膀胱癌相关基因的检测有助于膀胱癌的临床诊断、预后判断和治疗方法的选择。     

Survivin及Caspase-3在浅表性膀胱移行细胞癌中表达及预后意义

目的:探讨凋亡相关蛋白Survivin及Caspase-3在浅表性膀胱移行细胞癌表达及其临床意义.方法: 应用S-P免疫组织化学法检测47例行TUR-BT术切除膀胱移行细胞癌标本组织石蜡切片中Survivin和Caspase-3表达的情况,结合临床资料进行分析.所有标本均经病理证实为T1期内.10例正常膀胱黏膜为对照.结果: Survivin在膀胱移行细胞癌标本中的表达阳性率为68.1%(32/47),而正常对照组中无一例呈阳性表达;Caspase-3在膀胱移行细胞癌标本中表达阳性率为38.3%(18/47),与对照组阳性率90%(9/10)相比差异有统计学意义(P<0.05).Survivin表达与膀胱移行细胞癌的组织学分级、初发和复发显著相关(P<0.05),但与肿瘤数目无关;Caspase-3表达与膀胱移行细胞癌的初发复发相关,但与组织学分级、肿瘤数目无关.相关性分析表明,膀胱移行细胞癌中Survivin表达与Caspase-3表达呈负相关. 结论: Survivin在膀胱癌组织中选择性表达与膀胱移行细胞癌的分化程度密切相关,Caspase-3蛋白在膀胱移行细胞癌中表达下降,Survivin及Caspase-3蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义.     

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.