miRNA-130a与非小细胞肺癌侵袭转移相关研究进展

microRNA(miRNA)是近年来发现的一类长度为18-25个核苷酸的非编码小分子单链RNA。它主要通过与靶标基因3’UTR(非翻译区)的完全或不完全配对,降解靶标基因mRNA或抑制其翻译,从而参与调控个体发育、细胞凋亡、增殖及分化等生命活动。越来越多的实验证据表明,miRNA可通过调控其靶标基因参与的信号通路,影响肿瘤的发生和发展,发挥类似于癌基因或抑癌基因的功能。miRNA的发现为肿瘤发病机制的研究提供了新思路,也为肿瘤诊断和治疗提供了新的策略。本综述主要介绍miRNA-130a与非小细胞肺癌(non-small cell lung cancinoma,NSCLC)侵袭转移相关研究进展。     

微小RNA在肿瘤血管生成中的信号调控作用

微小RNA(miRNA)在转录后水平通过降解或抑制靶标信使RNA的翻译来介导基因的表达.肿瘤的血管生成涉及了一系列的信号调控通路,miRNA可能通过调控其靶基因所参与的信号通路影响肿瘤的血管生成.因此,研究肿瘤血管生成相关miRNA调控其靶基因所参与的信号通路在肿瘤的诊断及治疗中具有较高的价值.     

miRNA-148a与肿瘤

0 引言 当今,放化疗及生物靶向治疗已明显提高了肿瘤患者的生存期,但是肿瘤的复发、侵袭转移以及耐药等恶性行为仍是导致治疗失败与死亡的重要原因.microRNA(miRNA)是一类能调控基因表达的非编码蛋白RNA,通过调控mRNA表达和翻译的方式发挥作用.异常表达的miRNA广泛参与肿瘤的发生、发展、侵袭转移及耐药等演进过程.miRNA-148a作为miRNA中的一员,研究发现miRNA-148a在多种肿瘤中表达降低,主要发挥抑癌基因样作用,抑制并逆转肿瘤的恶性表型,其临床价值也越来越受到重视.     

MicroRNA-218通过EMT抑制肿瘤侵袭转移的研究进展

microRNA（miRNA）是非编码RNA,在基因转录后调节中发挥重要作用。miRNA在进化中具有高度保守性,能够通过与靶mRNA特异性碱基互补配对引起靶mRNA降解或抑制其翻译从而发挥对基因转录后表达调控作用。由于miRNA在血清和血浆中均很容易获得且在循环系统中miRNA作为稳定的标记物存在,故miRNA是一种很有前途的诊断因子。最新研究发现miR-218在多种恶性肿瘤（如肺癌、胃癌、肝癌、前列腺癌及结直肠癌等）的侵袭转移机制中发挥重要作用且多作为抑癌因子存在,但目前对miR-218在肿瘤侵袭转移中所涉及的具体作用靶点及相关通路的研究仍具有局限性。而上皮细胞-间充质转化（EMT）在上皮来源的恶性肿瘤的侵袭转移过程中发挥重要作用,本文就miR-218通过EMT途径在几种常见肿瘤侵袭转移机制中所涉及的作用靶点及相关通路作一简要综述,旨在为miR-218在恶性肿瘤的诊断及预后评估中的作用提供参考。     

miRNA介导肿瘤生物学行为改变的研究进展

MicroRNA(miRNA)是一类内源性非编码蛋白短链RNA,其基因转录后经过一系剪切转运过程形成成熟型的miRNA,并通过调控mRNA表达和翻译方式发挥许多重要的生物学效应。不同miRNA可呈现出癌基因或抑癌基因样功能,并有一定的组织特异性。多种恶性肿瘤的发生过程与miRNA表达谱的改变密切相关。miRNA调控着肿瘤的分化、增殖、凋亡、侵袭、转移及耐药等多种生物学行为。此外,一些miRNA对预测肿瘤患者的预后也有着重要的临床意义。     

MicroRNA对肿瘤基因的调控及其临床意义

微小RNA(microRNA,miRNA)通过调控基因的表达,参与细胞生命过程中一系列重要的进程,包括胚胎发育、细胞增殖和分化、细胞死亡与凋亡、体内生化代谢等。成熟miRNA通过RNA诱导的沉默复合体(RNA-induced silencing complex,RISC)结合到靶mRNA上,依赖于序列的互补性机制、剪切或阻遏靶mRNA、沉默基因的表达。miRNA与肿瘤等疾病的发生、发展密切相关。miRNA的表达谱在肿瘤细胞与正常细胞之间具有明显差异,起到类似于癌基因或抑癌基因的作用。miRNA通过沉默肿瘤侵袭转移相关基因的表达,参与肿瘤侵袭转移过程。肿瘤细胞在miRNA表达谱上的特异性为肿瘤的诊断提供了一项生物标志物,同时也为调控miRNA表达以治疗肿瘤提供了新的靶点。以miRNA为基础的抗肿瘤治疗还可与传统的化疗结合起来,提高肿瘤的治疗效果,为肿瘤的生物治疗开拓新视野。     

微小RNA-30a:肿瘤治疗的潜在靶点

微小RNA(miRNA)是长约20~25个核苷酸的内源性非编码RNA,主要通过抑制mRNA翻译和诱导mRNA降解而调节靶基因的表达,人类大约30%的基因受miRNAs调节。研究发现,大量miRNAs在肿瘤中表达失调,常常引起多种重要过程的紊乱,包括细胞增殖、侵袭与转移、凋亡以及耐药等。在肿瘤的发生过程中,不同的miRNA可能起着类似抑癌基因或者癌基因的作用,参与调节肿瘤细胞发生、发展等过程。miR-30a是miRNA的成员之一,通过调节靶基因的表达,参与调控肿瘤细胞增殖、转移和凋亡等过程。不同肿瘤血清中miR-30a的表达水平对肿瘤的早期诊断、治疗以及预后判断有着重要作用。此外,miR-30a的表达失调还与抗肿瘤药物耐药性的产生密切相关,推测其有望成为肿瘤治疗的一个潜在新靶标。本文就近年来miR-30a在肿瘤中作用的最新研究进展作一综述。     

微小RNA与DNA甲基化相互调控在胃癌中的作用

表观遗传修饰在胃癌发生发展及预后中起重要作用.微小RNA( miRNA)和DNA甲基化是表观遗传学的两个重要调控机制.miRNA抑制靶基因信使RNA的翻译,参与基因转录后水平调控.基因启动子区CpG岛的异常甲基化与肿瘤的发生关系密切,可导致癌基因、抑癌基因或其他肿瘤相关基因的表达异常.胃癌中存在miRNA和DNA甲基化...     

miR-21作用于PTEN与肿瘤耐药关系的研究进展

miRNA(microRNA)是一类非编码的微小RNA,其成熟体通过与靶mRNA 3' 端非编码区特异性结合,可在翻译和转录后水平调控靶基因的表达。有研究表明miRNA与细胞的发展、分化、凋亡和增殖有着密切的关系。miR-21(microRNA-21)作为miRNA的一个重要分子,在肿瘤的形成和耐药中发挥着重要作用。在众多耐药肿瘤细胞中,miR-21通过下调靶基因PTEN从而抑制肿瘤细胞的凋亡,增加肿瘤细胞的生长、转移和侵袭。本文就miR-21通过作于其靶基因PTEN与肿瘤耐药的关系作一综述。     

微RNA与肿瘤

微RNA(miRNA)是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

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。     

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.     

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.     

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。