C-kit和PDGFRβ在食管癌组织中的表达及其临床意义

背景与目的：有研究表明STI-571能抑制Bcr—Abl、C-kit、血小板衍生生长因子受体β（Platelet—derived grouth factor receptor—beta,PDGFRβ）的酪氨酸激酶．从而抑制细胞的分化增殖和促进细胞凋亡,本研究旨在检测与STI-571相关的酪氨酸激酶受体在食管癌中的表达情况。方法：应用免疫组化的方法,检测50例食管癌组织、癌旁组织和正常组织中与STI-571相关的酪氨酸激酶受体c—kit和PDGFRβ的表达。结果：c—kit在癌组织、癌旁组织、正常组织中的强表达率较低,分别为4％、4％、12％,表达的差异无统计学意义。PDGFRβ在癌组织、癌旁组织、正常组织中的强表达率分别为68％、28％、28％,表达的差异有统计学意义。应用Logistic回归的方法,发现c—kit或PDGFRl3在癌组织、癌旁组织、正常组织中的强表达率与患者的性别、年龄、肿物的分化程度、肿物的浸润深度、肿物的部位、淋巴结转移情况和分期无相关。结论：食管癌组织中PDGFRβ的强表达率较高,且明显高于癌旁组织和正常组织。食管正常组织中c—kit的强表达率较低,癌组织和癌旁组织中c-kit的强表达率更低。     

S100A4蛋白在肝癌组织中的表达及临床意义

目的:探讨SIOOA4蛋白在肝细胞癌、肝硬化、癌旁组织及正常肝组织中的表达及临床意义.方法:用组织芯片技术结合免疫组织化学法检测S100A4蛋白在肝癌相关组织中的表达差异,采用统计学方法分析其表达差异的临床意义.结果:免疫组织化学检测发现,S100A4蛋白在人原发性肝细胞癌、硬化肝组织、癌旁肝组织中表达较高,在正常肝组织中表达则很低,表达阳性率分别为70.2%、54.4%、41.7%和0.0%;统计学分析结果表明,S100A4蛋白表达影响肝癌患者的术后生存期,低表达患者的生存期比高表达患者延长.结论:S100A4蛋白在肝癌及相关组织中的表达率依次为,肝细胞癌＞癌旁肝＞肝硬化＞正常肝,在非微血管侵袭肝癌患者中S100A4阳性表达可明显降低其术后生存率.     

肝癌组织中Raf激酶抑制蛋白和磷酸化Raf 激酶抑制蛋白的表达及其意义

 目的探讨Raf激酶抑制蛋白（Raf kinase inhibitor protein,RKIP）和磷酸化Raf激酶抑制蛋白（Phosphorylated raf kinase inhibitor protein,P-RKIP）在肝细胞癌中的表达及其临床意义。方法应用组织芯片和免疫组织化学方法检测RKIP蛋白和磷酸化的RKIP蛋白在72例肝细胞癌组织、50例癌旁肝组织及16例正常肝组织中的表达,并分析RKIP的表达与肝细胞癌临床病理学特征的关系。采用Western blot方法检测36例肝细胞癌、36例癌旁组织及12例正常肝组织中RKIP蛋白和磷酸化的RKIP蛋白的表达。结果免疫组化结果显示肝细胞癌、癌旁及正常肝组织中RKIP的阳性率分别为22.2％、86％、93.8％,P-RKIP为29.2％、84％、93.8％;肝癌组织中RKIP和P-RKIP的表达显著低于癌旁及正常肝组织,差异有统计学意义（P<0.05）,而且肝癌组织和癌旁肝组织中两者蛋白的表达均呈显著正相关（P=0.000,P=0.005）;RKIP和P-RKIP的表达均与肝癌有无肝内或淋巴结转移及分化程度有关（P<0.05）。Western blot结果显示肝癌组织中RKIP和P-RKIP的表达显著低于癌旁及正常肝组织。结论RKIP和 P-RKIP表达的减少或缺失与肝癌的发生发展、侵袭转移密切相关。     

IGF—Ⅰ,IGF—Ⅱ及其受体在肝癌和癌旁肝组织中的表达

目的：探讨胰岛素样生长因子Ⅰ、Ⅱ及其受体在肝癌和癌旁肝组织中的表达其意义。方法：采用ＤＮＡ－ＲＮＡ原位杂交方法检测肝癌和癌旁肝中ＩＧＦ－Ⅰ、ＩＧＦ－Ⅱ及其本 ｍＲＮＡ的表达。结果：在肝癌组织中ＩＧＦ－Ⅰ、ＩＧＦ－Ⅰ受体、ＩＧＦ－Ⅱ、ＩＧＦ－Ⅱ受体ｍＲＮＡ的表达率分别为４０．０％、４６．７％、６６．７％和６３．３％，在癌旁肝组织中ＩＧＦ－Ⅰ、ＩＧＦ－Ⅰ受体，ＩＧＦ－Ⅱ、ＩＧＦ－Ⅱ受体ｍＲＮＡ的表达率     

C-KIT受体与恶性肿瘤

c-kit受体属Ⅲ型酪氨酸激酶受体家族，在人体许多正常细胞表面都有表达，与其配体干细胞因子结合后受体酪氨酸激酶功能区被激活，产生自身磷酸化，完成细胞内外的信呼传导，对这些细胞的分化发育以及功能维持起重要作用。近年来研究发现很多肿瘤细胞表面有c-kit受体的异常高表达，并发现了其编码基因的活化突变，推测突变与肿瘤的发生存在着一定的联系。本文综述了近年来c-kit受体在恶性肿瘤研究中的进展。     

肝癌组织雌激素受体表达与生物学特征的研究

目的 探讨雌激素受体（ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）在肝细胞肝癌（ｂｅｐａｔｏｃｅｌｌｕｌａｒ ｃａｒｃｉｎｏｍａ,ＨＣＣ）中的表达及其与ＨＣＣ生物学特征的关系。方法 用免疫组织化学方法检测了４３例ＨＣＣ及对应癌旁肝组织及４例正常肝组织的雌激素受体的表达,经大体及显微镜检查了这些肝细胞肝癌的病理特征。结果 雌激素受体阳性率在肝细胞肝癌为３７．２１％,癌旁肝组织为６０．４６％,正常肝组织     

B-myb C-myc在肝细胞性肝癌中的表达及临床意义

目的：检测肝细胞性肝癌（hepatocellular carcinoma，HCC）中B—myb及C—myc蛋白的表达情况，探讨其在肝癌发生、发展及转移中的作用。方法：采用免疫组化法检测60例肝癌组织及60例癌旁肝组织中B-myb和C-myc的表达情况，结果：B—myb、C—myc在癌组织中的阳性率分别为56．67％和53．33％，而在癌旁组织中的阳性率分别为36．67％和35．00％．癌组织与癌旁组织比较差异有显著性（P〈0.05）。B—myb在肝癌组织中的表达与临床分期、肝外转移、术后复发肿瘤个数及包膜完整相关（P均〈0．05）；C—myc在肝癌组织中的表达与门静脉癌栓、肝外转移、术后复发、肿瘤分化程度及包膜完整相关（P均〈0．05）。B—myb与C—myc在癌组织中的表达正相关。结论：B-myb及C—myc蛋白的过表达．可促使肝癌细胞增殖，使肝癌细胞具有更强的侵袭力，与肝癌的发生、发展密切相关。     

钙结合蛋白S100A13在肝癌组织中的表达及其临床意义

目的:探索钙结合蛋白S100A13(S100 calcium binding protein A13,S100A13)在肝癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法:收集广西医科大学第一附属医院34例HCC及相应癌旁组织、18例正常肝组织标本,商业购置197例肝癌及相应癌旁高密度组织芯片。应用原位RT-PCR技术检测HCC组织、癌旁组织、正常肝组织中S100A13 mRNA的表达,使用免疫组织化学技术检测HCC组织、癌旁组织、正常肝组织中S100A13蛋白的表达,并用Image-ProPlus软件分析免疫组织化学光密度值。结果:S100A13 mRNA在HCC、相应癌旁和正常肝组织中表达的阳性率分别为70.21%、51.06%和33.33%;S100A13 mRNA定位主要在胞核,多表达于核膜。S100A13蛋白在HCC、相应癌旁和正常肝组织中表达的阳性率分别为55.84%、38.96%及26.32%,HCC组织中的平均D值最高(0.038±0.051),其次是癌旁组织(0.022±0.034),正常肝组织(0.01±0.009)最低(P<0.05);S100A13蛋白主要表达于HCC细胞的胞质中,部分细胞核偶见表达,此外在癌旁次生胆小管中及部分炎细胞中也存在高表达。S100A13蛋白在HCC中的表达与患者的性别、年龄及病理分级无关。结论:HCC组织高表达S100A13蛋白,S100A13可能具有作为肝癌治疗靶点的潜力。     

肝癌及癌旁组织中端粒酶检测的临床意义

目的研究端粒酶作为原发性肝细胞癌（ＨＣＣ）肿瘤标志物的可能性。方法采用ＴＲＡＰ方法检测了３３例原发性肝细胞癌及其３３例癌旁组织、４例肝转移癌及其４例癌旁组织、６例肝良性肿瘤和６例正常肝组织中的端粒酶活性。结果３３例原发性肝细胞癌组织中，有３０例端粒酶表达阳性，其阳性率为９０．９％。３３例癌旁组织中，有９例端粒酶表达阳性，其阳性率为２７．３％。４例肝转移癌端粒酶活性均阳性，４例癌旁组织中，２例端粒酶表达阳性。６例肝良性肿瘤中，仅１例端粒酶表达阳性。６例正常肝组织端粒酶表达均阴性。肝癌组织端粒酶表达与肿瘤临床病理特征无关。结论肝癌组织中普遍存在端粒酶活性表达，而良性和正常肝组织中端粒酶活性较少表达。端粒酶有可能成为诊断原发性肝细胞癌的肿瘤标志物     

IGF-I、IGF-II及其受体在肝癌和癌旁肝组织中的表达

目的:探讨胰岛素样生长因子I、II及其受体在肝癌和癌旁肝组织中的表达及其意义.方法:采用DNA RNA原位杂交方法检测肝癌和癌旁肝组织中IGF-I、IGF-II及其受体mRNA的表达.结果:在肝癌组织中IGF-I、IGF-I受体、IGF-II、IGF-II受体mRNA的表达率分别为40.0%、46.7%、66.7%和63.3%,在癌旁肝组织中IGF-I、IGF-I受体、IGF-II、IGF-II受体mRNA的表达率分别为46.7%、53.3%、70.0%和73.3%,有36.7%的肝癌和50.0%的癌旁肝组织同时表达四种mRNA.IGF-I、IGF-II及其受体mRNA在分化较差的肝癌细胞、肝细胞再生结节和不典型增生肝细胞中阳性信号最强.结论:IGF-I、IGF-II及其受体在肝细胞癌变过程中发挥重要作用,肝癌的发生发展与IGF-I、IGF-IR、IGF-II、IGF-IIR的协同作用有关.     

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.     

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.     

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.     

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.     

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.     

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。     

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。     

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.