c-myc、ras基因与肝细胞癌的关系

癌基因的激活和抑癌基因的失活是原发性肝细胞癌(HCC)发生发展的分子生物学基础.加强对肝癌相关癌基因的研究,必然会加深我们对肝细胞癌变本质的认识,有助于从分子水平对肝癌进行早期诊断与防治.c-myc、ras基因是目前研究的热点之一,研究较多的是c-myc、ras基因对HCC发生和发展的影响.     

肝细胞恶性转化与监测分子标志

早诊早治是提高肝细胞癌患者生存率的唯一途径。随着基因组学、蛋白组学、转录组学和代谢组学等多种“组学”技术的进展，愈来愈多的肝细胞恶性转化相关分子标志被发现，并有望成为肝癌发生的预警监测及早期诊断的特异性生物标志。     

分子基因水平研究中医药防治肝癌的现状及展望

中医药治疗作为肝癌综合治疗的重要组成部分,有着鲜明的特色,现就近年来有关中医药防治肝癌分子基因水平研究现状作一简要概述和展望。 1 对癌基因、抑癌基因的影响 原发性肝癌的发生、发展是有众多的癌基因、抑癌基因参与其中,一些致病因子(如乙肝病毒、丙肝病毒)导致正常肝细胞基因损伤,引起相关癌基因的激活以及抑癌基因的失活是肝癌发生的分子生物学基础。若运用药物使异常表达     

肝癌特异诊断新标志物发现及其临床应用前景

肝细胞癌(hepatocellular carcinoma,HCC)是全球的最常见的肿瘤之一.虽经持续不懈地根除或改进多种治疗技术,肝癌患者的预后仍很差.如何监测肝细胞的恶性转化或早期诊断HCC仍是医学难题.HCC发病机制复杂,多种致病因素包括乙型肝炎病毒或丙型肝炎病毒的慢性持续感染、脂质积聚和黄曲霉素摄入等致使抗癌基因失活或癌基因复活,诱发肝细胞癌变;HCC患者的早期筛查有益于延长生存期.血甲胎蛋白(alpha-fetoprotein,AFP)和肝癌特异性AFP或A F P-L3作为肿瘤标志虽已常规应用,但他们诊断肝癌仍存在假阳性结果且灵敏度及特异性欠佳.肝癌的有效治疗取决于早期诊断,急需研发比较准确有效标志物用于肝癌患者的早期临床分期,治疗监测与预后判断.近来,积累的资料已显示新的血源性标志物如循环血肿瘤细胞,相关通路关键信号分子、癌胚型特异蛋白、长链非编码RNA和微小RNA对肝癌诊断的潜在价值.本文述评了肝癌特异诊断相关分子标志发现及其应用前景.     

基因标志物在肝癌诊断中的临床价值

肝癌的发生与肝炎病毒感染、致癌物作用、癌基因或癌相关基因激活、抗癌基因失活或胚胎期某些癌基因重新复活等诸多因素有关，并经启动、促进、演变多阶段的发病过程。临床匕肝癌确诊时已多属中、晚期，缺乏有效治疗，术后易复发及远处转移，预后较差，早诊断、早治疗至关重要。早期诊断和术后复发监测仍是临床研究的重点。[第一段]     

肝细胞癌的蛋白质组学研究进展

探讨肝癌发生发展和转移复发的分子机制,寻找早期诊断肝癌、预测转移的生物标记和干预治疗的靶点,已成为当今肝癌研究的热点.随着后基因组时代的来临,蛋白质组学为涉及多基因、多蛋白的肝细胞癌研究创造了新的契机.本文就肝细胞癌的蛋白质组学研究进展作简要综述.多基因、多蛋白的肝细胞癌研究创造了新的契机.本文就肝细胞癌的蛋白质组学研究进展作简要综述.     

肝细胞癌胰岛素样生长因子Ⅱ的蛋白和mRNA异常表达及其早期诊断价值

肝细胞癌（HCC）是由病毒、化学致癌物等多病因作用，因癌基因或癌相关基因激活、抗癌基因失活或胚胎期某些酶基因重新复活等诸多因素引起肝细胞生长失控而致癌变，经启动、促进、演变多阶段的发展过程，其中多种生长因子基因的调控和表达，与肝癌的发生、发展密切相关。胰岛素样生长因子（IGF）-Ⅱ基因在胎肝和新生儿肝脏中有大量表达，但出生后基因表达迅速降低直至关闭，     

MicroRNAs在肝细胞肝癌中作用的研究进展

MicroRNAs(miRNAs)是近年来发现的长度约为22 nt的一类非编码小分子RNA,通过在转录后或翻译水平调节靶基因功能,进而在生物个体发育、细胞增殖、凋亡、分化、肿瘤发生等生理及病理过程中发挥重要作用.miRNAs可能通过参与调控癌基因和抑癌基因的表达,促进恶性肿瘤的发生发展,或者其本身就是潜在的癌基因或抑癌基因.越来越多的研究显示miRNAs与肝细胞肝癌(hepatocellular carcinoma,HCC)关系密切.本文就miRNAs在HCC发生发展中的作用以及在HCC诊断与治疗中的应用价值等方面的研究进展作一综述.     

生物信号转导异常在肝癌发生发展中的作用

0 引言原发性肝细胞肝癌(HCC)的发生发展涉及到癌基因过度激活,抑癌基因的突变、缺失,以及细胞因子、粘附分子和细胞外基质分解酶等多因素、多环节和多基因协调或单独作用不同阶段的复杂过程,恶性程度高,发展迅速,早期诊断困难,临床治疗效果差,生存期短,复发和死亡率高,浸润、转移和复发是其治疗     

肝癌癌前病变相关癌基因及抑癌基因研究进展

原发性肝癌的早期诊断与治疗,仍是亟待解决的难题之一,肝癌癌前病变的深入研究在肝癌的早期防治方面有重要意义。一般认为在慢性肝病中出现的肝细胞不典型增生、腺瘤样增生、肝细胞再生结节、肝小多角细胞增生、肝细胞小管状化生、卵圆细胞增生和旱獭中的变异肝细胞灶,与肝细胞癌变的演化过程关系密切,因此,被认为属于肝癌癌前病变的范畴。肝癌的发生发展涉及多个癌基因和抑癌基因的参与,目前发现至少有９种癌基因及相关基因（Ｎ－ｒａｓ、Ｃ－ｍｙｃ、Ｃ－ｅｔｓ－２、Ｐ５３、Ｃ－ｆｍｓ、ＩＧＦ－Ⅱ、ＩＧＦ－ⅡＲ、ＴＧＦ－α、Ｒ…     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.