PTEN、NF-κBp65和CyclinD1在胃腺癌中的表达及其与肿瘤临床病理间的相关性

背景与目的:探讨PTEN、NF-κBp65和CyclinD1在胃腺癌组织中的表达及其与肿瘤临床病理特征之间的相关性.材料与方法:用免疫组织化学S-P法检测73例胃腺癌及20例正常胃粘膜组织中PTEN、NF-κBp65和CyclinD1的表达情况.结果:①PTEN在胃腺癌组织中蛋白表达阳性率为42.5%(31/73),明显低于它在正常胃粘膜组织中的阳性表达率90%(18/20)(P＜0.01);NF-κBp65和CyclinD1在胃腺癌组织中蛋白表达阳性率分别为58.9%(43/73)和60.3%(44/73),明显高于它们在正常胃粘膜组织中的阳性表达率20%(4/20)和25%(5/20)(P＜0 01);②PTEN与胃腺癌组织分化程度呈正相关(P＜0.01),与胃腺癌浸润深度、淋巴结转移及临床分期呈负相关(P＜0.01或P＜0.05);NF-κBp65与胃腺癌组织分化程度呈负相关(P＜0.05),与胃腺癌浸润深度、淋巴结转移及临床分期呈正相关(P＜0.05或P＜0.01);CyclinD1与胃腺癌的浸润深度相关(P＜0.05),与组织分化程度、淋巴结转移及临床分期无相关关系;③胃腺癌中PTEN的阳性表达率与NF-κBp65和CyclinD1均呈负相关(P＜0.05,P＜0.01),NF-κBp65与CyclinD1的阳性表达率呈正相关(P＜0.05).结论:PTEN、NF-κBp65和CyclinD1基因在胃腺癌的发生、发展中起着不同的作用;联合检测PTEN、NF-κBp65和CyclinD1,可能有助于对胃腺癌恶性程度的判定及侵袭转移能力的评估,进而为胃腺癌的预后分析和进一步治疗提供依据.     

抑癌基因PTEN、一氧化氮合酶与胃癌的关系及临床意义

目的检测抑癌基因PTEN编码蛋白、iNOS在正常胃粘膜及胃癌组织中的表达情况,探讨PTEN、iNOS与胃癌发生发展的关系及作用机理.方法采用免疫组织化学S-P法进行检测.结果 10例正常胃粘膜均可见PTEN蛋白的强表达,40例胃癌组织中28例PTEN蛋白表达较正常胃粘膜明显下降或缺失,差异有显著性(P＜0.01),与胃癌的分化程度、浸润深度、TNM分期、淋巴结转移显著相关(P＜0.05).iNOS在胃癌组织中的表达显著高于正常胃粘膜组,(72.5%vs10%,P＜0.01),与胃癌的浸润深度、淋巴结转移、TNM分期显著相关(P＜0.05).在PTEN蛋白阴性的胃癌组中,iNOS阳性率为93.8%,显著高于PTEN阳性组(P＜0.05).结论抑癌基因PTEN编码蛋白在胃癌及胃癌发展过程中表达逐渐下降或缺失,与iNOS之间可能存在相互作用,协同参与了胃癌的发展、转移及浸润.PTEN蛋白表达可作为判定胃癌生物学行为的临床参考指标.     

胃癌中PTEN、p27kip1及cyclinE蛋白表达及其意义

目的探讨PTEN、p27kipl及cyclinE蛋白表达与胃癌发生、发展的关系.方法应用免疫组化S-P法分别检测59例胃癌及癌旁组织中PTEN、p27kipl及cyclinE蛋白表达情况.结果PIEN在癌旁组织阳性率96.61%(51/59)显著高于胃癌组织中阳性率50.85%(30/59)(P＜0.05),胃癌组织中高中分化腺癌PTEN阳性率78.75%(15/19)显著高于低分化腺癌37.5%(9/24)与胃黏液癌37.5%(6/16)(P＜0.05),而后两者间无显著性差异(P＞0.05).p27kipl在癌旁组织阳性率84.75%(50/59)显著高于胃癌组织中阳性率47.46%(28/59)(P＜0.05),胃癌组织中高中分化腺癌p27kipl阳性率73.68%(14/19),显著高于低分化腺癌37.5%(9/24)与胃黏液癌31.25%(5/16)(P＜0.05),后两者间无显著性差异(P＞0.05).cyclinE在胃癌组织中阳性率55.93%(33/59)明显高于癌旁组织40.68%(24/59)(P＜0.05),胃癌组织中黏液癌阳性率68.75%(11/16)和胃低分化腺癌阳性率66.67%(16/24)显著高于胃高中分化腺癌阳性率31.58%(6/19)(P＜0.05),前两者间无显著性差异(P＞0.05).结论PTEN、p27kipl在胃癌组织中表达下降、cyclinE表达升高,随着病理分化程度降低PTEN、p27kipl表达降低,cyclinE表达升高,提示PTEN、p27kipl、cyclinE可能与胃癌的发生、发展及生物学行为有关.     

环氧合酶-2 mRNA在胃腺癌组织中表达的实验研究

目的探讨环氧合酶-2(COX-2)mRNA在胃腺癌组织及癌旁的正常胃粘膜组织中的表达及其意义.方法应用半定量逆转录-多聚酶链反应(RT-PCR)检测胃腺癌组织及病灶旁的正常胃粘膜组织中COX-2 mRNA的表达水平.应用Molecular Analyst软件定量分析RT-PCR产物电泳带,COX-2指数由COX-2和β-actin条带的积分吸光度值的比值来确定.COX-2指数大说明组织中COX-2 mRNA的表达水平高.结果胃腺癌组织的COX-2指数明显高于正常胃粘膜(P＜0.01).有淋巴结转移的胃癌组织COX-2指数显著高于无淋巴结转移者(P＜0.01);Ⅲ期和Ⅳ期的COX-2指数分别明显高于Ⅰ期及Ⅱ期(P＜0.05及P＜0.05).癌组织中COX-2 mRNA的表达水平与肿瘤的Borrmann分型、肿瘤浸润深度、分化程度、有无远处转移及肿瘤长径间无相关性(P＞0.05).结论 COX-2 mRNA的表达水平在胃腺癌组织中明显增高;其高表达与淋巴转移及临床TNM分期相关.     

胃癌及胃周转移淋巴结中环氧合酶-2的表达及其意义

目的检测环氧合酶-2(cyclooxygenase-2,COX-2)蛋白在胃癌组织、胃周淋巴结中的表达,探讨COX-2蛋白的表达与胃癌淋巴转移的关系.方法应用免疫组化方法(SP法)检测36例胃癌组织及病灶旁正常胃粘膜组织、80个胃周淋巴结中COX-2蛋白的表达.结果胃癌组织中COX-2蛋白的表达水平显著高于病灶旁正常胃粘膜组织,差异具有显著性(P＜0.01);有淋巴结转移的胃癌组织中COX-2蛋白的表达水平高于无淋巴结转移者,差异具有显著性(P＜0.05):有癌转移的淋巴结中COX-2蛋白的阳性表达水平高于无痛转移的淋巴结,差异具有显著性(P＜0.01).结论COX-2蛋白的过表达促进胃癌的淋巴结浸润和转移,影响胃癌的TNM分期,参与胃癌的演进.     

胃腺癌中P TEN 的表达与IGF ⅠR 的相关性

 目的　研究抑癌基因PTEN 和胰岛素样生长因子Ⅰ受体( IGF ⅠR) 在胃腺癌组织中的表达,探 讨PTEN 与IGF ⅠR 的相关性及其与胃癌临床病理学特征的关系。方法　采用免疫组织化学SP 法检 测60 例胃腺癌患者肿瘤组织和癌旁正常组织中PTEN 和IGF ⅠR 的表达水平。结果　60 例胃腺癌组 织中PTEN 蛋白表达阳性率仅为41. 7 % ,明显低于癌旁正常组织,两者差异有统计学意义( P = 0. 001) ; 其表达水平与年龄、性别无关( P > 0. 05) ,与分化程度( P = 0. 009) 、肿瘤浸润程度( P = 0. 001) 、淋巴结转 移( P = 0. 004) 和临床分期( P = 0. 002) 显著相关;在胃腺癌组织中IGF ⅠR 和PTEN 蛋白表达之间呈明 显负相关( rs = - 0. 469 P < 0. 001) 。结论　抑癌基因PTEN 的失活与胃癌的生物学行为密切相关; PTEN 可能对IGF ⅠR 的表达有着调控作用,联合检测两者可作为胃癌诊断、治疗和预后判断的参考指 标。     

GSK3β和CyclinD1在胃癌组织中的表达及临床意义

摘 要：［目的］ 探讨胃癌组织中GSK3β和CyclinD1的表达及其临床意义。［方法］ 采用免疫组织化学染色方法,检测胃组织芯片中（包括48例胃癌和对应正常胃组织及24例癌旁组织）GSK3β和CyclinD1蛋白的表达。［结果］ GSK3β和CyclinD1在胃癌组织中的表达率分别为35.4%和45.8%;GSK3β在癌组织中的阳性表达率明显低于正常胃组织和癌旁组织(P＜0.05),并与分化程度、组织学类型和淋巴结转移有关(P＜0.05);CyclinD1在胃癌组织中的阳性表达率则明显高于正常胃组织和癌旁组织,差异具有统计学意义(χ2=20.664,P＜0.05);CyclinD1的表达则与TNM分期和淋巴结转移相关（P＜0.05）。GSK3β与CyclinD1蛋白的表达呈负相关性(r=-0.331,P＜0.05)。［结论］ GSK3β和CyclinD1在胃癌的进展、分化、浸润和转移中起重要作用,是判断胃癌生物学行为的良好指标。     

HIF-1α和VEGF在胃癌中的表达及临床意义

背景与目的:低氧是肿瘤中存在的普遍现象,肿瘤的进展与癌组织中缺氧诱导因子1 α(HIF-1 α)和血管内皮生长因子(VEGF)的表达有密切关系,本研究探讨HIF-1 α和VEGF在胃癌浸润、转移过程中的机制及其相互作用.方法:采用免疫组化SP(streptavidin perotridase)法检测85例胃癌组织和85例癌旁正常胃组织(距癌灶5 cm以上)中HIF-1 α和VEGF的表达.结果:(1)癌旁组织中HIF-1 α的表达均为阴性,胃癌组织中的阳性表达率为76.47%(65/85),显著高于癌旁组织,差异有统计学意义(P＜0.05).(2)HIF-1 α在胃癌中表达阳性率与胃癌的临床分期、浸润深度和淋巴结转移有关(P＜0.05),与胃癌细胞分化程度无关(P＞0.05).(3)癌旁组织中VEGF的表达均为阴性,在胃癌组织中的表达阳性率为60.00%(51/85),显著高于癌旁组织,差异有统计学意义(P＜0.05).(4)VEGF在胃癌中表达阳性率与胃癌的临床分期、浸润深度和淋巴结转移有关(P＜0.05),与胃癌细胞分化程度无关(P＞0.05).(5)85例胃癌组织中HIF-1 α蛋白的阳性率为76.47%,VEGF蛋白阳性率为60.00%,其中共同阳性者为45例,HIF-1α阳性而VEGF阴性者为20例,VEGF阳性而HIF-1α阴性者为6例,共同阴性者为14例,经相关性分析发现,两者具有正相关性(r=0.367,P＜0.05).结论:HIF-1 α与VEGF的表达率均随着胃癌浸润深度、淋巴结转移和临床分期的发展而增高,它们共同参与了胃癌的发生、发展,可作为胃癌浸润和转移的重要判定指标.HIF-1 α可能通过上调VEGF的蛋白表达,促进胃癌血管生成而促进胃癌的转移,抑制HIF-1 α的表达可能是治疗胃癌的新手段.     

端粒酶基因hTRT在胃癌中的表达及其临床意义

目的 探讨胃癌中端粒酶基因hTRT mRNA表达与临床参数的关系，评价hTRT表达检测在胃癌诊断中的价值。方法 用原位杂交的方法检测端粒酶基因hTRT mRNA在胃癌、癌旁组织和胃良性病变中的表达和分布情况。结果 57例胃癌中hTRT基因表达阳性率为94.7%(54/57)；57例癌旁组织中hTRT基因表达阳性率为05（0／57）；69例胃良性病变中hTRT基因表达阳性率为2.9%(2/69)。胃癌组织中hTRT基因的表达与癌旁组织、胃良性病变比较差异有显著性（P均＜0.001)。胃癌组织中hTRT的表达与肿瘤分化程度、淋巴结转移相关（P均＜0.05)，但与肿瘤分期无相关性（P＞0.05)。hTRT表达的阳性分级与淋巴结转移相关（P＜0.01)。但与胃癌分化程度和分期无相关性（P均＞0.05)。结论 端粒酶基因hTRT表达检测在胃癌诊断中可能有一定的价值。     

E-cadherin在胃腺癌组织中的表达及其临床意义

目的:探讨上皮钙黏蛋白E（E-cadherin）在胃腺癌组织中的表达及其临床意义。方法:收集61例我院胃腺癌组织和其癌旁正常组织的石蜡包块以及患者的临床病理资料。免疫组化法检测E-cadherin在胃腺癌组织及癌旁正常组织中的表达,通过自动化图像分析系统对结果进行定量分析,统计学分析E-cadherin的表达及其与胃癌临床病理特征的关系。结果:E-cadherin在胃癌组织表达明显低于相应的癌旁组织（P＜0.05）;E-cadherin的表达下调与胃腺癌TNM分期、分化程度和浸润深度相关（P＜0.05）,与性别、年龄、淋巴结转移无明显相关（P＞0.05）。结论:E-cadherin在胃腺癌组织中表达下调,提示E-cadherin可能在胃癌的侵袭过程中起重要作用。     

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.     

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。     

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.     

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.     

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.