食管鳞状细胞癌中热休克蛋白10和60的表达及其意义

目的探讨食管鳞状细胞癌中热休克蛋白(HSP)10、60的表达及其意义。方法应用免疫组化:EnVision二步法,观察168例食管鳞状细胞癌和42例切缘食管黏膜中HSP10、60的表达,并比较其阳性率。结果 HSP10在食管鳞状细胞癌和切缘食管黏膜表达率分别为53．8％和 37．5％,统计学分析结果表明差异无显著意义(P>0．05);HSP60在食管鳞状细胞癌和切缘食管黏膜表达率分别为92．7％和63．2％,统计学分析结果表明差异有显著意义(P<0．01)。在高、中、低分化食管鳞状细胞癌中HSP10、60的表达差异均无显著意义(P>0．05),两者的表达与食管鳞状细胞癌区域淋巴结转移无关(P>0．05)。结论 HSP60在食管鳞状细胞癌的表达高于切缘食管黏膜,提示其在食管鳞状细胞癌的发生发展中起作用。HSP10、60的表达与食管鳞状细胞癌分化程度、区域淋巴结转移无关。     

热休克蛋白在食管鳞癌中的表达及其意义

目的探讨热休克蛋白（HSPs）HSP27、HSP60、HSPT0和HSP90d在食管鳞癌及其切缘正常食管黏膜中的表达及其意义。方法168例食管鳞癌和42例切缘正常食管黏膜制成组织芯片,应用免疫组化EnVision法及Westernbolt检测HSP27、HSP60、HSP70和HSP90α在组织中的表达情况,分析4种HSPs的表达与肿瘤位置、肿瘤长度、浸润深度、分化程度和淋巴结转移的关系。结果食管鳞癌和切缘正常食管黏膜中,HSP27的阳性率分别为62．0％和42．1％;HSP60的阳性率分别为92．7％和63．2％;HSP70的阳性率分别为57．9％和22．2％;HSP90α的阳性率分别为33．7％和18．5％。统计学分析结果表明,HSP60和HSP70在食管鳞癌的表达均高于切缘正常食管黏膜（P〈0．01）,HSP27和HSP90α在食管鳞癌与切缘正常黏膜的表达差异均无统计学意义（P〉0．05）。除HSP27的表达随着食管鳞癌分化程度的降低而降低（P〈0．05）外,其他3种HSPs的表达与食管鳞癌的临床病理特征无关（P〉0．05）。结论HSP27、HSP60、HSPT0和HSP90α在食管鳞癌和切缘正常食管黏膜中均有表达。HSP60和HSP70在食管鳞癌的表达高于切缘正常食管黏膜,可能与食管鳞癌的生物学行为有关;HSP27的表达随食管鳞癌分化程度的降低而降低,HSP27的高表达可能影响鳞癌的分化程度。     

下咽鳞状细胞癌组织中△Np63和TAp63蛋白的表达及临床意义

目的探讨下咽鳞状细胞癌（HSCC）和下咽乳头状瘤及正常下咽黏膜中△Np63和TAp63蛋白的表达及其在下咽鳞状细胞癌发病机制中的作用。方法采用免疫组织化学SP法检测34例下咽鳞状细胞癌、5例下咽乳头状瘤及8例下咽正常黏膜组织中△Np63和TAp63蛋白的表达情况。结果（1）△Np63蛋白在下咽正常黏膜、乳头状瘤及下咽癌组织中的阳性细胞百分数为（21．6±12．5）％,（43．6±10．2）％和（75．3±24．5）％,其阳性细胞百分数越高,组织分化程度越低（P〈0．05）,但阳性细胞百分数的高低与TNM分期、淋巴结转移无关（均P〉0．05）;（2）TAp63蛋白在下咽正常黏膜、乳头状瘤及下咽癌组织中的阳性表达率为（14．5±10．2）％,（13．6±5．2）％和（6．7±5．2）％,其阳性细胞百分数越低,组织分化程度越低（P〈0．05）,但阳性细胞百分数的高低与TNM分期、淋巴结转移无关（均P〉0．05）。结论p63的异常表达可能参与了下咽鳞状细胞癌发生的早期阶段,△Np63的过度表达及TAp63的表达下调在下咽鳞状细胞癌的形成机制中有重要作用,并与下咽癌的分化程度相关,但与临床分期及淋巴结转移无关。     

蛋白水解诱导因子在食管鳞状细胞癌中的表达

目的：研究蛋白水解诱导因子（proteolysis-inducing factor,PIF）在食管鳞状细胞癌中的表达及意义。方法：应用免疫组化方法,检测PIF在107例食管鳞状细胞癌病人癌组织以及其中35例癌旁正常组织以及8例食管良性疾病标本中的表达情况,并探讨PIF表达与食管癌临床分期、肿瘤分化程度的关系。结果：食管鳞状细胞癌组织中存在PIF表达,其表达与食管良性疾病对照组中的表达差异有统计学意义（P〈0．05）,肿瘤组织中表达PIF的个体其癌旁正常组织中亦有PIF表达,PIF表达在肿瘤分化、是否侵及浆膜层、有无淋巴结转移和肿瘤分期中的差异无统计学显著性（P〉0．05）。结论：食管鳞状细胞癌组织中存在PIF表达,其表达与肿瘤分化、是否侵及浆膜层、有无淋巴结转移和肿瘤分期无关。     

转移抑制因子KAI1和E-Cadherin在食管癌组织中的表达及其意义

目的 探讨KAI1和E-Cadherin在食管癌中的表达及其意义。方法 用免疫组化S-P法检测KAI1和E-cadherin蛋白在60例食管癌及对应的食管正常黏膜组织中的表达情况。结果 在食管鳞癌组织中KAI1表达（50％）显著低于食管正常黏膜组织（81．67％）（P〈0．01）。食管一常组织中E-cadherin表达（80％）显著高于癌组织（41．67％）（P〈0．01）。KAI1低表达与食管癌病理分级、淋巴结转移及食管癌浸润深度无关（P〉0．05）；E-cadherin低表达与食管癌病理分级、淋巴结转移密切相关（P〈0．05），与食管癌浸润深度无关（P〉0．05）；两者表达皆与食管癌的人体分型无关（P〉0．05）。KAI1与E-cadherin表达无明显相关性（P〉0．05）：结论 E-cadherin的低表达与食管癌的淋巴结转移有关；KAI1低表达未见对食管癌浸润转移的影响；两者无协同作用。     

p-JNK JNK和PPAR γ在食管癌变过程中的

目的：探讨p-JNK JNK和PPAR γ蛋白在食管癌变过程中的表达及其意义。方法：采用免疫组织化学方法，研究食管正常鳞状上皮（15例）、食管鳞状上皮内瘤变（85例）和食管鳞状细胞癌（60例）组织中p-JNK JNK和PPAR γ蛋白的表达情况。结果：JNK在食管正常鳞状上皮、食管鳞状上皮内瘤变和食管鳞状细胞癌中的阳性表达率分别为20．0％、37．6％和55．0％，而p-JNK的阳性表达率分别为33．3％、55．3％和73.3％，JNK和p-JNK在食管鳞状细胞癌中的阳性表达率均明显高于食管正常鳞状上皮和食管鳞状上皮内瘤变（P〈0．05）。高级别食管鳞状上皮内瘤变中JNK、p-JNK的阳性表达率显著高于食管正常鳞状上皮和低级别食管鳞状上皮内瘤变（P〈0．05）。PPAR γ在食管正常鳞状上皮、食管鳞状上皮内瘤变和食管鳞状细胞癌中的阳性表达率分别为733％、45．9％和45．0％，食管鳞状上皮内瘤变和食管鳞状细胞癌中PPAR γ的阳性表达率明显低于食管正常鳞状上皮（P〈0．05）。食管鳞状细胞癌中JNK、p-JNK和PPAR3,的表达与肿瘤分化程度相关，JNK、p-JNK和PPAR3,的表达均随肿瘤病理分级的增高而降低（P〈0．05）。JNK、P—JNK和PPAR γ的表达与临床病理特征不相关（P〉0．05）。结论：在食管癌变过程中，JNK、p-JNK的表达呈增高趋势而PPAR γ的表达呈下降的趋势。但食管鳞状细胞癌中JNK／p—JNK和PPAR γ,的表达均随肿瘤分化程度降低而降低。提示JNK、p-JNK和PPAR γ在食管鳞状上皮癌变和进展过程中发挥不同作用，其机制比较复杂。     

食管鳞状细胞癌组织中整合素β1和上皮钙粘附素表达与侵袭和转移的关系

目的：探讨食管鳞状细胞癌组织中整合素β1（integrinβ1，INTβ1）和E-cd表达与侵袭和转移的关系。方法：应用免疫组化SP法检测54例食管鳞状细胞癌及8例正常食管黏膜组织中INTβ1和上皮钙粘附素（epithelial cadherin，E-cd）的表达，分析其与临床病理特征的关系。结果：54例食管鳞状细胞癌组织中INTβ1正常表达率为18．5％（10／54），E-cd为25．9％（14／54）；8例正常食管上皮组织中INTβ1正常表达率为5／8，E-cd为7／8，差异均有统计学意义，P〈0．05。食管鳞状细胞癌组织中INTβ1（rs=-0、313，P=0．021）和E-cd（rs=-0．342，P=0．011）表达程度与组织学分级呈负相关；E-cd与淋巴结转移呈负相关，rs=-0．289，P=0．034。结论：食管鳞状细胞癌组织中INTβ1和E-cd蛋白表达降低，影响肿瘤细胞分化、生长、侵袭和转移。     

CK1δ与COX-2在食管鳞状细胞癌的表达及其意义

目的：探讨CK1δ与COX-2蛋白在食管鳞状细胞癌中的表达与食管癌临床病理特征之间的关系。方法：用免疫组织化学方法（SP法）检测了63例食管鳞状细胞癌手术切除的癌组织、癌旁组织（30例正常食管上皮、19例羟度不典型增生、14例重度不典型增生组织）中的CK1δ与COX-2的蛋白的表达。并采用流式细胞术对其中随机选取的40例癌组织、18例轻度不典型增生组织、12例重度不典型增生组织和20例正常食管上皮组织进行上述两种蛋白的定量分析，采用SPSS11．5软件进行统计学处理。结果：在正常食管上皮组织中CK1δ和COX-2蛋白的表达显著低于轻度不典型增生组织、重度不典型增生组织和癌组织（P〈0．01），轻度不典型增生组织显著低于癌组织（P〈0．01），轻度不典型增生组织与重度不典型增生组织比较差异无显著（P〉0．05）．重度不典型增生组织和癌组织的比较差异无显著性（P〉0．05）。在癌组织中。淋巴结转移组中CK1δ蛋白的表达显著高于无淋巴结转移组（P〈0．01）．CK1δ蛋白的表达与分化程度和有无纤维膜的侵及无关（P〉0．05）；淋巴结转移组中COX-2蛋白的表达显著高于无淋巴结转移组（P〈0．01），有纤维膜侵及组中COX-2蛋白的表达显著高于无纤维膜侵及组（P〈0．01），COX-2蛋白的表达与分化程度无关（P〉0．05）。在食管鳞癌组织中CK1δ蛋白与COX-2蛋白之间呈显著正相关（r=-0．482，P〈0．01）。结论：CK1δ、COX-2蛋白的异常表达可能共同参与了食管鳞癌的发生、发展与转移，有望成为评价食管癌恶性程度和转移的指标。     

MMP-2、TIMP-2在口腔鳞状细胞癌中表达的临床病理研究

[目的]研究口腔鳞状细胞癌（OSCC）组织中基质金属蛋白酶-2（MMP-2），基质金属蛋白酶组织抑制因子-2（TIMP-2）的表达。[方法]采用免疫组化SP法检测60例OSCC、35例非典型增生、20例止常口腔黏膜中MMP-2、TIMP-2的表达情况。[结果]OSCC中MMP-2、TIMP-2的表达均高于非典划增生组（P〈0．05），在非典型增生组中表达高于正常口腔黏膜组（R＜0．05）。MMP-2的表达与肿瘤细胞分化程度、淋巴结转移密切相关（P〈0．05），与年龄、肿瘤大小、TNM分期无关（P〉0．05）。TIMP-2与肿瘤的淋巴结转移密切相关（P〈0．05），与年龄、肿瘤大小、肿瘤细胞分化程度、TNM分期无关（P〉0．05）。淋巴结转移组中MMP-2／TIMP-2比值显著高于无淋巴结转移组（P〈0．05）。[结论]MMP-2、TIMP-2是OSCC转移的重要生物学标志，MMP-／TIMP-2比值对评估淋巴结转移的潜能有重要意义。     

P16蛋白在食管鳞状细胞癌的表达及意义

目的探讨多肿瘤抑制基因P16／MTS1在食管鳞状细胞癌形成中的作用。方法采用免疫组织化学方法，对51例食管鳞状细胞癌及其16例淋巴结转移癌进行了P16蛋白多克隆抗体免疫组织化学染色。结果P16蛋白在食管鳞状细胞癌中呈低表达，阳性率为45．1％（23／51），阳性率显著低于正常食管粘膜及癌旁组织（P＜0．01），在各组织学分级的食管癌中阳性率分别为：Ⅰ级66．7％（14／21），Ⅱ级34．8％（8／25），Ⅲ级14．3％（1／7），Ⅰ级显著高于Ⅱ级（P＜0．05），P16蛋白阳性率与肿瘤分化程度呈负相关（P＜0．01），与肿瘤浸润、转移无相关性。结论食管癌中有频发的P16基因失活，致基表达下降，并与组织分化程度有关，而与肿瘤浸润、转移无密切关系     

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.