肿瘤发生发展的分子机理(1)

为了适应机体需要,生物体对细胞增殖进行着十分精妙的调节。幼年动物的细胞增殖超过了细胞死亡,使得动物体积增大;成年动物的细胞增殖与死亡达到平衡,以此来维持相对稳定状态。成熟细胞的增殖速度也不尽相同,小肠上皮细胞的增殖速度很快,半衰期仅有几天时间,有些白细胞也以同样的速度更新;有些细胞的增殖速度则较慢,人类红细胞的半衰期约100d,健康肝细胞几乎很少死亡,成年后的脑细胞死亡速度十分缓慢且几乎不能更新。细胞增殖的精确调控偶尔可能会出现异常,1个细胞可以无视机体的需要而无节制的生长和分裂。当具有这样遗传倾向的细胞增殖,将…     

肿瘤发生发展的分子机理(3)

生长因子基因的异常表达可以刺激细胞增殖一般情况下,编码生长因子的基因几乎都不太可能成为癌基因,只有sis基因例外。编码PDGF蛋白的癌基因sis可以使表达PDGF受体的自体细胞增殖,这种自身刺激作用被称为细胞生长的自分泌诱导作用。     

肿瘤发生发展的分子机理(2)

人体内的原癌基因与肿瘤抑制基因编码许多种蛋白控制细胞的生长和增殖,在诱导癌变过程中起关键作用．原癌基因获得显性表达功能和肿瘤抑制基因丧失隐性表达功能的突变是致癌的。人类已经具有了解每一种肿瘤的特征基因改变的能力,并因此可以深入研究肿瘤发生和进展机制,全面改进肿瘤的早期诊断。     

肿瘤发生发展的分子机理(5)

众所周知,肿瘤细胞的许多重要生长基因和细胞周期调控基因存在插入、缺失、点突变等遗传异常。一些基因常被异常扩增并出现染色体断裂和易位,产生癌性的嵌合蛋白。多数肿瘤细胞也缺乏一个或多个DNA修复系统,并因此产生大量突变的累积,此外,肿瘤细胞中的关卡调控机制也可出现缺陷,使DNA损     

肿瘤发生发展的分子机理(6)

肿瘤研究的主要目的是为了寻找对肿瘤有效的预防和治疗措施。     

肿瘤发生发展和转移过程中的分子进化机制

肿瘤的发生发展和转移是肿瘤细胞不断进化的过程,伴随着大量分子进化事件的发生,使肿瘤细胞逐渐获得生存与增殖优势,并促进了肿瘤异质性的形成.深入理解肿瘤分子进化机制将有助于人们更清楚地认识肿瘤发生发展和转移的内在机制,开发针对性的治疗策略,阻断肿瘤的发展和转移,提升治疗效果.本文总结了肿瘤发生发展和转移过程中的基因突变、基...     

肿瘤发生的遗传机理

本从癌基因和抑癌基因两方面综述了肿瘤发生的遗传机理,旨在使人们培养“防重于治”的健康理念。     

获得性植物病害抗性的分子机理

获得性植物病害抗性的分子机理吴中华马自兰（安徽省生物工程中心实验室,合肥２３００３１）自然条件下,植物与各种潜在的病原微生物有着广泛和经常的接触。从这个角度来看,植物病害的发生频率是很低的。这是因为在大多数情况下,微生物致病能力的缺乏和植物有效的抵御...     

Molecular biology of nickel carcinogenesis

A review of the molecular mechanisms of nickel carcinogenesis has been compiled. This work is based upon approximately 20 years of research conducted in my laboratory. Molecular mechanisms of nickel carcinogenesis are considered from the pointofview of the uptake of nickel, both soluble and insoluble particles in cells, its dissolution and its effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing in cells by DNA hypermethylation in mammalian cells and by inhibiting histone acetylation in yeast cells are also discussed.     

Molecular mechanisms of nickel carcinogenesis

A brief review of the molecular mechanisms of nickel carcinogenesis is presented. Molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of nickel-induced gene silencing by DNA hypermethylation in mammalian cells and by its ability to inhibit histone acetylation. Model systems designed to study the molecular mechanism of gene silencing are discussed.     

Molecular models in nickel carcinogenesis

Nickel compounds are known human carcinogens, but the exact molecular mechanisms of nickel carcinogenesis are not known. Due to their abundance, histones are likely targets for Ni(II) ions among nuclear macromolecules. This paper reviews our recent studies of peptide and protein models of Ni(II) binding to histones. The results allowed us to propose several mechanisms of Ni(II)-inflicted damage, including nucleobase oxidation and sequence-specific histone hydrolysis. Quantitative estimations of Ni(II) speciation, based on these studies, support the likelihood of Ni(II) binding to histones in vivo, and the protective role of high levels of glutathione. These calculations indicate the importance of histidine in the intracellular Ni(II) speciation.     

Molecular mechanisms in urinary bladder carcinogenesis

Urinary bladder cancer accounts for approximately 5% of all newly diagnosed malignancies in the developed world. Smoking, occupational exposure and dietary factors constitute the most important exogenous risk factors for bladder carcinogenesis. Yet, individuals with seemingly equal exposure to environmental carcinogens develop bladder cancer in an unpredictable manner. This is probably attributed to the fact that DNA repair capacity varies in human populations, pointing the role of genetic susceptibility in human cancer. Numerous studies demonstrated that certain genetic and epigenetic alterations are fairly constant. Loss of heterozygosity (LOH) at chromosome 9 is an aberration found in urothelial cell carcinoma (UCC) of all stages and grades as well as in dysplastic urothelium, possibly representing an early event in urinary bladder carcinogenesis. On the contrary, gains of 3p can only be found in tumors demonstrating highly malignant behavior. Microsatellite instability (MSI) is another frequent finding in urinary bladder cancer. This has led many investigator groups to employ the analysis for MSI for early diagnosis of UCC with promising results. The silencing of certain genes such as p16(INK4A) and DAPK by aberrant methylation of their promoter region also represents an important mechanism in carcinogenesis. Similarly, alterations in certain tumor suppressor genes and proto-oncogenes result in uncontrolled cell proliferation, reduced apoptosis and have been associated with more aggressive UCC phenotypes. Undoubtedly, the application of these observations in clinical practice will make a breakthrough in the management of bladder cancer.     

Molecular mechanisms of metal toxicity and carcinogenesis

Many metals and metal-containing compounds have been identified to be potent mutagens and carcinogens. Recently, a new sub-discipline of molecular toxicology and carcinogenesis has been developed. The combination of newly developed molecular techniques and free radical approach makes it possible to insightfully examine metal-induced carcinogenesis in precise molecular terms so that intricate biological interrelationships can be elucidated. In consideration of the increased amount of new findings deciphered by utilizing these new methods, the 1st Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis was held. In this conference, more than 50 scientists from nine countries presented their novel discoveries concerning metal-induced carcinogenesis, delineated molecular mechanism of metal carcinogenesis, and proposed novel therapeutic intervention and prevention strategies. This article reviewes some of the state-of-the-art information presented at the meeting regarding the molecular mechanisms of metal cytotoxicity and carcinogenesis.     

Homologous recombination as a mechanism of carcinogenesis

Cancer develops when cells no longer follow their normal pattern of controlled growth. In the absence or disregard of such regulation, resulting from changes in their genetic makeup, these errant cells acquire a growth advantage, expanding into pre-cancerous clones. Over the last decade many studies have revealed the relevance of genomic mutation in this process, be it by misreplication, environmental damage or a deficiency in repairing endogenous and exogenous damage. Here we discuss homologous recombination as another mechanism that can result in loss of heterozygosity or genetic rearrangements. Some of these genetic alterations may play a primary role in carcinogenesis, but they are more likely to be involved in secondary and subsequent steps of carcinogenesis by which recessive oncogenic mutations are revealed. Patients whose cells display an increased frequency of recombination also have an elevated frequency of cancer, further supporting the link between recombination and carcinogenesis. In addition, homologous recombination is induced by a wide variety of carcinogens, many of which are classically considered to be efficiently repaired by other repair pathways. Overall, homologous recombination is a process that has been widely overlooked but may be more central to the process of carcinogenesis than previously described.