端粒酶在肿瘤疾病中的表达及研究进展

端粒酶是近年来发现的与肿瘤发生发展密切相关的一种逆转录酶 ,已成为肿瘤研究的热点。目前的研究表明[1 ] ,已知 85 %的人肿瘤组织发现了端粒酶活性的表达 ,而与肿瘤相邻的正常组织或良性病变仅为 4%左右 ,这种显著的相关性提示端粒酶在肿瘤细胞恶性状态的形成和发展中起着关键作用。现将端粒、端粒酶与肿瘤发生的机制、端粒酶的检验方法 ,近年来端粒酶在肿瘤疾病中的表达及研究进展以及治疗前景加以综述如下。1　端粒、端粒酶与肿瘤发生的机制端粒是真核细胞染色体末端的特殊结构 ,像二顶帽子盖在染色体两端 ,在染色体复制及保护染色体稳…     

端粒酶在癌症诊治中的应用前景

Kim等[1 ] 1994年建立的抗酒石酸磷酸酶(TRAP)检测端粒酶的方法极大地推动了端粒酶及其功能的研究。本文介绍了端粒酶在癌症诊治中的应用前景。1　端粒和端粒酶端粒是真核细胞染色体末端的DNA-蛋白质结构,其作用是保护和稳定染色体末端。脊椎动物的端粒DNA由数百至数千个6碱基(     

端粒/端粒酶--抗肿瘤药物设计的新靶点

端粒是染色体末端具有TTAGGG重复序列的特殊结构，它对维护染色体完整并在细胞老化和肿瘤中起着重要作用。端粒酶是一种带有内源RNA及蛋白组分的特殊逆转录酶，研究证实它在80％－90％的肿瘤细胞中呈高水平表达，而在正常体细胞中检测不到。因此端粒／端粒酶已成为抗肿瘤药物的新靶点，综述端粒／端粒酶的结构和功能、各种有效抑制端粒／端粒酶的途径及其研究现状。     

端粒、端粒酶与皮肤肿瘤

端粒 (telomere)是真核细胞染色体末端的特殊结构 ,具有保护染色体、维持染色体稳定性的重要作用。端粒的不断缩短或丢失 ,可阻止细胞的增殖 ,活化的端粒酶则以自身 RNA为模板 ,不断合成端粒。通常正常体细胞无端粒酶活性 ,端粒酶的活化与细胞衰老、永生化和癌变密切相关。本文     

端粒酶活性检测方法研究进展

端粒是真核细胞染色体的线性DNA分子末端,有着重要的生物学功能,对维持染色体稳定、防止染色体末端融合和保证DNA完整复制起着重要作用。端粒酶(telom-erase)是使端粒延伸的反转录DNA合成酶,是一种核糖核酸蛋白复合体。端粒酶以其RNA组份为模板,以端粒3′末端为引物,在其具有逆转录酶活性的蛋白组份的催化下合成端粒重复序列。近年来大量研究表明,端粒酶广泛表达于各类恶性肿瘤细胞,但人正常细胞一般阴性,是目前应用最广、最特异的肿瘤标志物。有文献报道,端粒酶     

端粒酶活性在宫颈癌中的初步研究

目前 ,研究端粒酶活性与表达程度对肿瘤防治、诊断、延缓衰老有重要意义 ,是国内外医学生物学界研究的一个热点。染色体端区 (telom ere)又称端粒 ,是存在于真核生物线性染色体末端的一种特殊结构 ,而人类染色体末端普遍存在端区结构。它具有保持染色体、防止染色体降解或端间融合的功能。人类体细胞端区随着年龄的增长而缩短 ,导致染色体稳定性下降 ,肿瘤的发病率升高。肿瘤细胞致癌性变化的主要决定因素是染色体基因的结构和功能的变化 ,其中肿瘤抑制基因的缺失与肿瘤细胞的致癌性关系密切。较多的研究表明 ,端粒酶和肿瘤细胞之间存在相互…     

端粒酶和端粒酶抑制剂

端粒是染色体末端独特的DNA－蛋白质结构,其主要作用为保护染色体的完整性和维持细胞的复制能力。端粒酶是由RNA和蛋白质亚基构成的,能够延长端粒的一种特殊反转录酶。端粒酶激活见于大多数的人类恶性肿瘤组织中,而正常组织细胞中无端粒酶活性。因此认为端粒酶激活对于维持多数肿瘤组织细胞增殖能力是必不可少的。同时,端粒酶也成为肿瘤化学治疗的新靶点。抑制端粒酶的策略不少,用反义寡核苷酸阻断端粒酶RNA的模板作用就是一个切入点;抑制端粒酶催化蛋白亚单位则可能是抑制其活性的另一手段。另外,一些可能的端粒酶抑制剂亦已见报道,例如,核苷类似物,蛋白激酶C抑制剂,细胞分化诱导剂等。尽管不少机制尚待明确,但前景依然光明。     

端粒、端粒酶与肿瘤

端粒和端粒酶与人类的衰老和肿瘤的发生发展有着极为密切的关系，端粒是一种封闭真核染色体末端的脱氧核糖核酸，对染色体起保护作用，端粒酶是一种特异的染色体末端转移酶，它的存在解决了染色体末端复制缩短问题，同时认为端粒酶的过度表达与细胞的永生化和癌变直接相关。因此，有关端粒和端粒酶的深入研究对肿瘤的诊断和治疗有着极其重要的意义。本文对端粒和端粒酶的结构与功能，及其在细胞癌变中的重要作用进行了综述。     

端粒酶与肺癌

近来年 ,端粒酶与肿瘤相关性研究是肿瘤分子生物学领域的热门课题。正常人体组织中仅生殖细胞、部分造血干细胞及胚胎胎儿时期显示端粒酶活性 ,而恶性肿瘤细胞中端粒酶活性特异性增多。1　端粒与端粒酶端粒 (Tebomere)是真核生物染色体DNA分子末端的特殊结构 ,对维持染色体稳定性和DNA完整复制具有重要作用。这一特殊序列是 2 0世纪 30年代分别由Muller和Mc cIntock发现 ,并由前者命名为端粒 ,由丰富的蛋白质和重复的简单序列DNA构成。 1 988年查明人类染色体端粒序列主要由 5′-TTAGGC - 3′片段重复构成 ,Herley等发现重复序列为 …     

反义寡核苷酸和小分子干扰RNA作为端粒酶抑制剂的研究进展

端粒酶是真核生物染色体末端的核蛋白结构,能够指导合成重复的端粒序列TTAGGG,而细胞的复制与端粒长度的维持有关。已有大量关于端粒酶的研究,很多临床前试验已将抑制端粒酶活性作为治疗恶性肿瘤的一个新的治疗方案。本文综述了反义寡核苷酸(ASODN)和小分子干扰RNA(siRNA)作为端粒酶抑制剂的研究进展,并进一步讨论了携载ASODN及siRNA基因载体的应用及其优缺点。     

Benorylate hydrolysis by human plasma and human liver.

1. Benorylate (4-acetamido phenyl-O-acetylsalicylate) hydrolysis in vitro by human plasma and by human liver microsomes and cytosol has been investigated. 2. Benorylate was hydrolysed by a route involving initial hydrolysis of the acetyl group to yield phenetsal followed by hydrolysis to paracetamol and salicylate. Hydrolysis via acetylsalicylate was minor. 3. Benorylate was more actively hydrolysed by liver cytosol than microsomes and about 10 times faster than plasma. 4. Following a single oral dose benorylate (4 g) to volunteers only salicylate and paracetamol were detected in the plasma. 5. The therapeutic effects of benorylate appear to be mediated by salicylate and paracetamol.     

Priming effect of recombinant human interleukin-2 and recombinant human interferon-gamma on human neutrophil superoxide production

The effect of recombinant human interleukin-2 (rhIL-2) and recombinant human interferon-gamma (rhIFN-gamma) were evaluated on superoxide (O2-) production of human polymorphonuclear neutrophils (PMNs). Ten minutes incubation with rhIL-2 showed a dose-dependent enhancement of n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O2-production of human PMNs, and the rate of enhancement reached 49.6% at the concentration of 3000 U/ml rhIL-2. Same pretreatment with rhIFN-gamma also showed a dose-dependent enhancement of FMLP-induced O2-production of human PMNs, and the maximal rate of enhancement was 47.0% at the concentration of 3000 U/ml rhIFN-gamma. Any cytokines given alone did not induce O2- production. These cytokines showed no enhancement of phorbol myristate acetate (PMA)-induced O2- production, neither. The effects of these cytokines to FMLP-induced O2- production were kept in calcium-free medium. Moreover, incubation with these cytokines caused no elevation of intracellular free calcium concentration [( Ca++]i) in resting PMNs. Incubation with them did not change the increase of [( Ca++]i) of PMNs induced by FMLP significantly, neither. Recombinant forms of cytokines are used clinically, now. These results may be helpful for the use of them.     

Antitumor effects of recombinant human prolactin in human adenocarcinoma-bearing SCID mice with human NK cell xenograft

To survey the immune regulatory function of recombinant human prolactin (rhPRL) and its potential application in adoptive immunotherapy, CB17-SCID mice were loaded with human colon adenocarcinoma HT-29 cells (5 x 10(5) cells/mouse, i.p.) 24 h before adoptive transfer with the purified human NK cells followed by rhPRL injection (10 mug/mouse, every other day for a total of 10 injections). Upon analysis, rhPRL did not exert any direct inhibitory effects on HT-29 cells but slightly improved the tumor cell growth both in vitro and in vivo. After SCID mice were reconstituted with human NK cells, rhPRL improved the antitumor effects of human NK cells in HT-29-bearing SCID mice, showing a prolonged survival from 70.4 to 112.1 days, and the increased survival rate from all died to 40% survival for more than 160 days. rhPRL improved the proliferation of human NK cells with or without PHA stimulation. rhPRL also directly enhanced the cytotoxicity of human NK cells against HT-29 tumor cells in 4-h coculture. The supernatant of rhPRL-stimulating NK cells inhibited the proliferation of HT-29 cells through, at least partly, the interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatant. Thus, rhPRL administration in HT-29 tumor-bearing SCID mice promotes the antitumor effects of adoptively transferred NK cells.     

Effect of human kidney lipids on human kidney renin activity

The major lipids of human kidney tissue were isolated by solvent extraction, and the lipid composition was determined by thin-layer chromatographic techniques. The positional distribution of fatty acyl groups in ethanolamine and choline phosphatides was determined after enzymatic hydrolysis. Major phosphatides were assayed for plasmalogen content. Triglycerides were characterized by argentation chromatography. The fatty acyl composition of these lipids was also determined. The effect of intact triglycerides, phospholipids, 1- and 2-monoacyl phosphatides and ether lipids on renin activity in vitro was determined by incubations with 3-[U¹⁴C]valyl tetradecapeptide renin substrate. Kidney triglycerides, 1-monoacyl and 2-monoacyl phosphatidylethanolamines and phosphatidylcholines significantly inhibited renin activity. The renin-inhibitory effect of these lipids was comparable to inhibition by hog kidney phospholipid inhibitor. The intact phospholipids and cholesterol potentiated human kidney renin activity. Phosphatidylserines and synthetic glyceryl ether lipids have no significant effect. These results indicate that lipid-induced inhibition of human renin activity does not require the ethanolamine moiety, acyl group unsaturation, or the presence of a hydroxyl group at the 2-position. Additionally, no specific structure-activity relationships can describe lipid-renin interactions.     

The human indoleamine 2,3-dioxygenase gene and related human genes

Tryptophan oxidation occurs via both extra-hepatic and hepatic pathways. Although these pathways share many enzymes, the first and rate-limiting step in each pathway is carried out by two different enzymes: Indoleamine-Pyrrole 2,3 Dioxygenase (INDO) and Tryptophan 2,3-Dioxygenase (TDO2). Over the course of the last forty years extensive and detailed research by many groups have led to an understanding of some of the important biologic functions of these pathways and their metabolic products. One of the tasks that now lie ahead is linking variations in these genes with variable human responses in different disease states. This short review will focus on known aspects of the INDO and TDO2 gene structure and variability. In addition to INDO and TDO2 a third related gene, the Indoleamine-Pyrrole 2,3 Dioxygenase-like 1 (INDOL1) gene will be discussed. INDOL1 is a gene of unknown function that lies adjacent to INDO on chromosome 8.     

Inhaled human insulin

The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human insulin is associated with an increase in insulin antibody titers, especially in patients with type 1 diabetes. These increases are not associated with any clinical sequelae. Patient satisfaction data have shown that inhaled human insulin is associated with greater treatment satisfaction relative to subcutaneous insulin in patients with type 1 or type 2 diabetes. This review summarizes the current data on the clinical efficacy and safety of inhaled human insulin in patients with type 1 or type 2 diabetes.