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Following a TRAIL: Update on a ligand and its five receptors   总被引:28,自引:0,他引:28  
Identification of tumour necrosis factor apoptosis inducing ligand (TRAIL), a TNF family ligand, sparked a torrent of research, following an initial observation that it could kill tumour cells, but spare normal cells. Almost a decade after its discovery, and with five known receptors, the true physiological role of TRAIL is still debated and its anti-tumorigenic properties limited by potential toxicity. This review takes a comprehensive look at the story of this enigmatic ligand,addressing its remaining potential as a therapeutic and providing an overview of the TRAIL receptors themselves.  相似文献
组蛋白乙酰化与癌症   总被引:17,自引:0,他引:17       下载免费PDF全文
由于组蛋白被修饰所引起的染色质结构的改变,在真核生物基因表达调控中发挥着重要的作用,这些修饰主要包括甲基化、乙酰化、磷酸化和泛素化等,其中组蛋白乙酰化尤为重要.组蛋白乙酰转移酶(HAT)和组蛋白去乙酰化酶(HDAC)参与决定组蛋白乙酰化状态.HAT通常作为多亚基辅激活物复合体的一部分,催化组蛋白乙酰化,导致染色质结构的松散、激活转录;而HDAC是多亚基辅抑制物复合体的一部分,使组蛋白去乙酰化,导致染色质集缩,并抑制基因的转录. 编码这些酶的基因染色体易位易于导致急性白血病的发生.另一方面,已经确定了一些乙酰化修饰酶的基因在染色体上的位置,它们尤其倾向定位于染色体的断裂处.综述了HAT和HDAC参与的组蛋白乙酰化与癌症发生之间关系的最新进展,以期进一步阐明组蛋白乙酰化修饰酶的生物学功能以及它们在癌症发生过程中的作用.  相似文献
The role of nitric oxide in cancer   总被引:16,自引:0,他引:16  
Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interest-ingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties.Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis by upregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53,poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understand-ing at the molecular level of the role of NO in cancer will have profound therapeutic implications for the diagnosis and treatment of disease.  相似文献
高聚生研发历程述评及其用于癌症治疗的理论基础   总被引:16,自引:1,他引:15  
高聚生是用金葡菌培养物制成的一种全新的抗癌产品,在国际上属首创;其有效成份经证实为含于其中的一种超级抗原,即金葡菌的C型肠毒素。本文介绍了高聚生的研发历程,并着重谈了该产品用于癌症治疗的理论基础,与国外研发中的同类产品比较,以及高聚生今后发展的展望。  相似文献
Histone deacetylases (HDACs) and histone acetyl transferases (HATs) are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.  相似文献
InterestintraditionalChineseherbalremedieshasboomedin the western countries. It is very important to study theirmolecular mechanisms and purify effective compoundswith new knowledge and new techniques to meet a greatneed for human health. Ephedrine, the f…  相似文献
抑制素基因的研究进展Advances on Inhibin Genes   总被引:13,自引:1,他引:12       下载免费PDF全文
薛昱  储明星  周忠孝 《遗传》2004,26(5):749-755
抑制素是性腺分泌的一种糖蛋白激素,它具有抑制垂体促卵泡素合成和分泌的作用。本文介绍了抑制素α亚基基因(INHA)、抑制素βA亚基基因(INHBA)、抑制素βB亚基基因(INHBB)的克隆、结构、定位、多态性、表达、分子调节及其与繁殖性能和癌症的关系。绵羊INHA、INHBA和INHBB基因分别被定位到2q41→q43、4q26和2q31→q33。INHA、INHBA和INHBB基因对绵羊产羔数都有显著的影响。抑制素βB亚基基因突变的雌性小鼠有明显的发育和繁殖缺陷。INHA 基因与妇女卵巢早衰显著相关。 Abstract:Inhibins are gonadal glycoprotein hormones belonging to the transforming growth factor-βsuperfamily that act to suppress pituitary follicle-stimulating hormone synthesis and secretion. In this paper, we briefly introduced the cloning, structure, localization, polymorphism, expression, molecular regulation of inhibin-α(INHA), -βA (INHBA) and -βB (INHBB) subunit genes and their relationships with reproductive performance and cancer. The inhibin genes (INHA, INHBA and INHBB) had significant effect on litter size in sheep. The ovine INHA, INHBA and INHBB genes had been mapped to chromosomes 2q41→q43, 4q26 and 2q31→q33, respectively. The female mice carrying INHBB mutations suffered from distinct developmental and reproductive defects. The INHA gene was significantly associated with premature ovarian failure in women.  相似文献
Therapy of cancer by cytokines mediated by gene therapy approach   总被引:12,自引:0,他引:12  
Qian C  Liu XY  Prieto J 《Cell research》2006,16(2):182-188
Gene therapy offers a new approach for treatment of cancer. Transfer of genes encoding immunostimulatory cytokines has been used with remarkable success to eliminate cancer in animals. However, clinical trials in patients with this strategy had limited efficacy. Therefore, improvement ofgene transfer vector system is necessary. A hybrid viral vector, consisting of SFV replicon with either murine IL-12 or reporter LacZ gene, was constructed. This hybrid vector showed specificity and high level of expression in HCC both in vitro and in vivo. In a rat orthotropic liver tumor model, treatment of established tumors by the hybrid vector with raiL- 12 gene resulted in a strong anti-tumor activity without accompanying toxicity. Subsequently, a helper-dependent adenovirus vectors containing a mifepristone (RU486) inducible system was constructed for controlled and liver-specific expression of human interleukin 12 (hIL- 12) (HD-Ad/RUhIL- 12) and mouse IL-12 (mIL-12) (HD-Ad/RUmIL-12). Data showed that high and sustained serum levels of hlL-12 could be attained by continuing administration of RU486 every 12 or 24 h. Repetitive induction ofhlL-12 could be obtained over, at least, a period of 48 weeks after a single injection of HD-Ad/RUhlL-12. Treatment of liver metastases with of HD-Ad/RUmIL- 12 plus RU846 resulted in complete tumor regression in all animals. Then, different cytokine genes were inserted into conditional replicative adenoviruses vectors (also called oncolytic adenovirus). Replication ofadenovirus in tumor cells would kill tumor cells and release viruses, which infect surrounding tumor cells. The combination of cytopathic effect by oncolytic adenovirus and biological effect of transgene would exert strong antitumor activity. These new types of vectors may provide a potent and safe tool for cancer gene therapy.  相似文献
番茄红素与癌   总被引:12,自引:0,他引:12  
番茄红素是主要的类胡萝卜素之一,最近的科学研究发现,它对人类健康有重要的作用。本文介绍了番茄红素的食物来源、生物合成、物理化学特性和生理活性,它的抗癌效果与其抗氧化活性有关。很多的流行病学研究证明,番茄红素对一些类型的癌有预防效果,如前列腺癌和消化道癌。体内和体外的癌细胞培养研究也支持这一结论。因此,具有广泛用途的番茄红素,将有希望成为最重要的一个化学防癌物质。  相似文献
广州市饮用水源中硝酸盐亚硝酸盐含量与癌症死亡率联系   总被引:12,自引:0,他引:12  
本文探讨了饮用水源中硝酸盐和亚硝酸盐污染对癌症死亡率的影响。收集了1991~1998年广州市饮用水源中硝酸盐、亚硝酸盐和癌症死亡率的历史数据,并分析了它们之间的相关性。结果显示,饮用水源中硝酸盐氮和亚硝酸盐氮的总浓度与癌症死亡率呈正相关关系(R~2=O.76,P<0.05)。对广州市各区的数据分析表明,饮用水源中亚硝酸盐氮和癌症死亡率有较高的相关性(R~2=0.56,P<0.05),且硝酸盐氮和癌症死亡率的相关性也很高(R~2=0.66,P<0.01)。这说明了1991~1998年期间,广州市区居民癌症死亡率的逐年递增很可能与饮用水源中硝酸盐和业硝酸盐含量的增加有关。此次研究结果说明饮用水源中的硝酸盐及亚硝酸盐可能是重要的致癌因子。  相似文献
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