胃黏膜癌变过程中Survivin与Fas表达及其相关性

目的探讨凋亡基因Survivin、Fas在胃黏膜癌变过程中的表达、临床意义及其两者的相关性。方法采用免疫组化法检测12例正常组织、136例患者（包括浅表性胃炎22例、肠上皮化生25例、异型增生37例及胃癌52例）组织中的Survivin和Fas表达。结果Survivin在肠上皮化生、异型增生和胃癌中的阳性率分别为16％、37．8％和69．2％。胃癌组明显高于肠上皮化生（P〈0．01）和异型增生组（P〈0．05）。胃癌组Fas表达率为30．8％，显著低于对照组和异型增生组（均P〈0．01）。Survivin表达和淋巴结转移、远处转移密切相关（均P〈0．05）；Fas表达和淋巴结转移密切相关（P〈0．05）。相关回归分析显示胃癌组织病理分期中Survivin与Fas表达呈负相关。结论在胃黏膜癌变过程中，Sur-vivin的表达逐渐上调，而Fas的表达逐渐下调。在胃癌组织中Survivin和Fas的表达呈负相关。     

胃癌及癌前病变细胞凋亡与Caspase-9，Bax表达的关系

目的：探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用。方法：应用免疫组化S—P法检测Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法（TUNEL法）检测相应胃组织细胞凋亡。结果：Caspase-9蛋白在非癌胃黏膜组（慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生）阳性表达率分别为100．00％、86．67％、50．00％、42．85％,呈逐渐下降趋势。慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异（P〈0．05）,肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异（P〉0．05）。Bax蛋白在48例非癌胃组织中的阳性表达率分别为：慢性浅表性胃炎100．00％、慢性萎缩性胃炎80．00％、肠上皮化生56．25％、不典型增生57．14％,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异（P〈0．05）。慢性浅表性胃炎、慢性萎缩性胃炎、肠匕皮化生、不典型增生、胃癌组织中,AI值（细胞凋亡指数）分别为（14．72±2．68）％、（10．02±2．34）％、（7．55±2．80）％、（6．09±2．35）％、（3．26±1．23）％,呈逐渐下降趋势,有显著性差异（P〈0．05）。结论：Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生。     

凋亡抑制蛋白Survivin在胃癌中的表达及其与bcl-2、p53蛋白相关性研究

目的：研究凋亡抑制蛋白Survivin、bcl-2、p53在胃癌组织中的表达及其与临床病理特征之间的关系，并探讨Survivin与bcl-2、p53蛋白表达的相关性。方法：采用链霉菌抗生物素蛋白-过氧化酶连接（S-P）免疫组化方法，检测Survivin、bcl-2、p53蛋白在正常胃粘膜组织及胃癌组织中的表达。结果：Survivin蛋白在正常胃粘膜组织中无表达，而在58例胃癌中41例（70．7％）表达阳性，差异有统计学意义（P〈0．01）；Survivin蛋白表达与胃癌组织病理分化程度、淋巴结转移、TNM分期相关，而与浸润程度不相关；胃癌bcl-2蛋白表达的阳性与阴性中，Survivin蛋白表达阳性率分别为81．0％（34／42）和43．8％（7／16），两者比较差异显著（P〈0．01）；p53蛋白表达的阳性和阴性中，Survivin蛋白表达阳性率分别为58．1％（18／31）和22．2％（6／27），两者比较亦有显著性差异（P〈0．05），Survivin蛋白的表达与胃癌组织中的bcl-2蛋白及p53蛋白表达密切相关。结论：Survivin蛋白异常表达可引起细胞凋亡抑制，在胃癌的发生中起一定作用，其过度表达提示胃粘膜细胞增生极度活跃；Sur-vivin蛋白表达与胃癌中bcl-2蛋白及p53蛋白的异常表达密切相关。     

Hp感染与胃癌及癌前病变中p53、bcl-2、c-myc基因表达关系的研究

目的：研究幽门螺杆菌（Hp)感染的胃癌及癌前病变患者胃粘膜p53,bcl-2,c-myc基因的表达，以探讨Hp在胃癌发生，发展过程中的作用机制，方法：应用免疫组化方法测定60例胃癌组织，18例异型增生，29例肠上皮化生，35例萎缩性胃炎，29例浅表性胃炎组织中Bcl-2,c-myc基因蛋白表达情况，PCR／SSCP测定p53基因第5－8外显子突变，Hp阳性由快速尿素酶法和HE染色确定，结果：胃癌组Hp阳性41例，阴性19例，在胃癌组织中p53,bcl-2,c-myc基因阳性表达分别为38例（63．3％），38例（63．3％），18例（30．0％），p53,c-myc基因在胃癌中阳性表达率显著高于异型增生（P＜0．05）,bcl-2在异型增生组织中的阳性表达率与胃癌，肠上皮化生相比无显著性差异（P＞05），p53,bcl-2,c-myc基因表达与胃癌分期，淋巴结转移均无显著性关系（P＞0．05），但bcl-2与胃癌类型，分化程度显著相关（P＜0．05），每一种病变类型Hp阳性组p53,bcl-2,c-myc基因蛋白的阳性表达率均高于Hp阴性组，两者之间有显著性差异（P＜0．05），结论：Hp感染者具有更多肿瘤生物学行为，可以引起抑癌基因p53第5－8外显子突变，癌基因c-myc，凋亡调节基因bcl-2表达增加,Hp可能为促癌剂，在胃癌的发生发展中起一定作用。     

RASSF1A基因在胃癌中的表达及临床意义

目的：研究RASSF1A蛋白在胃癌中的表达及临床病理学意义。方法：采用免疫组化SP法检测69例胃癌组织，慢性浅表性胃炎（CSG）和慢性萎缩性胃炎（CAG）各15例，伴肠化生（IM）15例和伴异型增生（DYS）19例胃粘膜组织中RASSF1A蛋白的表达。结果：胃癌组织中RASSF1A表达的阳性率为56．5％（39／69），低于其在CSG胃粘膜组织中的阳性表达率86．7％（13／15）（P〈0．05）；从CSG→CAG→IM→DYS→GC这一演化模式过程中，RASSF1A蛋白的阳性率表达逐渐降低（P〈0．05）；RASSF1A表达与肿瘤分化程度及有无淋巴转移相关（P〈0．005）。结论：RASSF1A在胃癌中低表达可能参与肿瘤的发生、发展和预后有关系。     

肠特异性转录因子CDX2在不同亚型肠化生及胃癌组织中的表达

背景与目的：肠化生被认为是胃癌的癌前病变,而肠特异性转录因子CDX2在肠上皮的形成、分化及肠表型的维持方面有重要作用。近年来研究发现CDX2在慢性萎缩性胃炎（chronic atrophic gastritis,CAG）相关的肠化生中呈高水平表达,在部分胃癌组织中也有表达,提示其可能与胃粘膜上皮由胃表型向肠表型的转化,以及胃癌的发生有关。本研究旨在探讨CDX2在胃粘膜肠化生发生、进展及胃癌发生中的作用,进一步明确肠化生与胃癌发生的关系。方法：选择46例CAG伴肠化生、40例胃癌及32例对应癌旁肠化生,构建组织芯片。分别用高铁二铵／爱先蓝（HID／AB）及HE染色对肠化生及胃癌进行分型．然后用免疫组化和原位杂交检测不同亚型肠化生及胃癌中CDX2蛋白及mRNA的表达。结果：癌旁肠化生中Ⅲ型肠化生的比例显著高于CAG伴肠化生（分别为56．25％和21．74％,P〈0．01）。CDX2蛋白阳性率在CAG伴肠化生、癌旁肠化生和胃癌中分别为69.56％、53．13％和42．50％：CDX2 mRNA阳性牢分别为63．04％、46．87％和35．00％。胃癌中显著低于CAG伴肠化生（P〈0．01）,而与癌旁肠化生无显著性差异（P〉0．05）。CDX2表达与胃癌组织类型有关联,肠型胃癌显著高于弥漫型（P〈0．05）。Ⅲ型肠化生中CDX2蛋白表达显著低于Ⅰ型（P〈0．05）。结论：CDX2在胃粘膜肠化生发生及进展为胃癌过程中可能有重要作用。     

EphA2/EphrinA1在胃癌中的表达及其意义

目的：探计EphA2及其配体EphrinA1在胃癌组织中的表达及与胃癌临床病理特征的关系。方法：利用免疫组织化学法检测82例胃癌手术切除标本的癌组织、癌旁组织及正常胃粘膜内EphA2、EphrinA1和E-cadherin的表达；并采用流式细胞术对其中随机选取的45例标本进行上述三种蛋白的定量分析，采用SPSS软件进行统计学处理。结果：胃癌组织中EphA2、EphrinA1的表达明显高于癌旁组织及正常胃粘膜（P〈0．01），而癌旁组织与正常胃粘膜之间无显著性差异（P〉0．05）；E—cadherin在胃癌组织中的表达明显低于癌旁组织和正常胃粘膜（P〈0．01），而癌旁组织与正常胃粘膜间无显著性差异（P〉0．05）。在胃癌组织中，随分化程度的降低，EphA2、EphrinA1蛋白的表达均显著升高（P〈0．05），而E-cadherin蛋白的表达则显著降低（P〈0．05）；随浸润深度的增加，EphA2、EphrinA1蛋白的表达均显著升高（P〈0．05），而E-cadherin蛋白的表达显著降低（P〈0．05）；淋巴结转移组中EphA2、EphrinA1蛋白的表达显著高于无淋巴结转移组（P〈0．05），而E-cadherin蛋白的表达则显著低于无淋巴结转移组（P〈0．05）；EphA2、EphrinA1和E-cadherin蛋白的表达与肿瘤直径、患者的性别和年龄无关（P〉0．05）EphA2与E—cadherin蛋白的表达呈显著负相关（r=-0．231，P〈0．01），EphrinA1与E-cadherin蛋白的表达呈显著负相关（r=-0．403，P〈0．01），EphA2与EphrinA1蛋白的表达呈显著正相关（r=0．707，P〈0．01）。结论：EphA2／EphrinA1与E-cadherin蛋白表达异常可能共同参与了胃癌的发生、发展与转移；联合捡测三种蛋白对于评价胃癌的恶性程度、判断其转移潜能具有一定的参考价值。     

胃癌中 Survivin 和 Cox-2 的表达与临床病理因素的关系

目的：探讨凋亡抑制蛋白Survivin和Cox-2在胃癌中的表达及其相关性与临床意义。方法：采用免疫组织化学sP法检测Survivin和Cox-2蛋白在60例胃癌和20例切缘正常的胃粘膜中的表达。分析Sur-vivin和Cox-2表达与胃癌临床病理因素的关系及两者的相关性。结果：胃癌组织和切缘正常的胃粘膜中，Survivin蛋白阳性率分别为68．3％和0％；Cox-2蛋白阳性率分别为80．O％和1．7％。统计学分析结果表明，Survivin和Cox-2在胃癌的表达均高于切缘正常的胃粘膜（P〈0．01）。Survivin蛋白在胃癌中表达阳性率与性别、年龄、肿瘤大小等因素无关（P〉0．05），但与肿瘤分化程度、浆膜侵犯、淋巴结转移密切相关（P〈0．05）。Cox-2蛋白在胃癌中的表达阳性率与性别、年龄、肿瘤大小、肿瘤分化程度、浆膜侵犯等因素无关（P〉0．05），但与淋巴结转移密切相关（P〈0．05）。胃癌中Survivin与Cox-2之间具有显著正相关性（P〈0．05）。结论：Survivin蛋白和Cox-2蛋白在胃癌的发生发展中起重要作用。Survivin蛋白与Cox-2蛋白表达密切相关，二者可能存在共同的激活机制，构成肿瘤细胞凋亡的多种途径。二者的检测可作为反映胃癌生物学行为和判断预后的有效指标之一。     

胃癌中Survivin和Cox-2的表达与临床病理因素的关系

目的：探讨凋亡抑制蛋白Survivin和Cox-2在胃癌中的表达及其相关性与临床意义。方法：采用免疫组织化学sP法检测Survivin和Cox-2蛋白在60例胃癌和20例切缘正常的胃粘膜中的表达。分析Sur-vivin和Cox-2表达与胃癌临床病理因素的关系及两者的相关性。结果：胃癌组织和切缘正常的胃粘膜中，Survivin蛋白阳性率分别为68．3％和0％；Cox-2蛋白阳性率分别为80．O％和1．7％。统计学分析结果表明，Survivin和Cox-2在胃癌的表达均高于切缘正常的胃粘膜（P〈0．01）。Survivin蛋白在胃癌中表达阳性率与性别、年龄、肿瘤大小等因素无关（P〉0．05），但与肿瘤分化程度、浆膜侵犯、淋巴结转移密切相关（P〈0．05）。Cox-2蛋白在胃癌中的表达阳性率与性别、年龄、肿瘤大小、肿瘤分化程度、浆膜侵犯等因素无关（P〉0．05），但与淋巴结转移密切相关（P〈0．05）。胃癌中Survivin与Cox-2之间具有显著正相关性（P〈0．05）。结论：Survivin蛋白和Cox-2蛋白在胃癌的发生发展中起重要作用。Survivin蛋白与Cox-2蛋白表达密切相关，二者可能存在共同的激活机制，构成肿瘤细胞凋亡的多种途径。二者的检测可作为反映胃癌生物学行为和判断预后的有效指标之一。     

CyclinE 在胃癌中的表达及其与临床生物学行为关系的研究

目的：研究胃癌组织中CyclinE蛋白的表达及其与胃癌临床生物学行为的关系。方法：采用免疫组织化学方法（sP法）检测胃癌组织和正常胃粘膜中cyclinE蛋白的表达。结果：CyclinE蛋白阳性表达率在胃癌中（59％）显著高于正常胃粘膜（0％）（P〈0．01）；CyclinE蛋白表达与胃癌患者性别、年龄、肿瘤发生部位、大小及大体分型均无关（P〉0．05）。与胃癌分化程度、浸润深度、淋巴结转移、PTNM分期及术后5年生存率相关（P〈0．05或P〈0．01）。结论：CyclinE蛋白的异常表达参与了胃癌的发生、发展。检测cyclinE蛋白表达，对胃癌侵袭和转移的早期诊断、预后评估及治疗靶向的发展具有重要意义。     

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.     

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.