TRAIL及其在白血病治疗中的研究进展

肿瘤坏死因子相关凋亡诱导配体(TRAIL)是近几年研究较热的抗肿瘤新型生物制剂,通过其死亡受体诱导肿瘤细胞凋亡,而对正常细胞无毒性,且与化疗药物具有协同性,但也存在抵抗机制.该文就TRAIL的生物学特点及其受体、TRAIL诱导肿瘤细胞凋亡的机制以及TRAIL在白血病治疗中的进展作一综述.     

化疗药物外诱导白血病细胞凋亡的研究

目的 研究化疗药物诱导白血病细胞凋良的作用及其与Ｒｃｌ－２表达,临床预后指标及临床疗效的关系。方法 利用形态学观察、ＤＮＡ琼脂糖凝胶电凉、凋亡指示抗体ＡＰＯ２,７结合流式细胞仪检测法,研究临床治疗相关剂量的化疗药物诱导急性淋巴细胞白血病（ＡＬＬ）细胞,急性混合性白血病（ＨＡＬ）细胞的凋亡及其Ｒｃｌ－２表达率。结果 （１）用临床治疗相关剂量的长春新碱（ＶＤＲ）、地塞米松（Ｄｅｘ）、柔红霉素（ＤＮＲ）     

小儿白血病化疗药物的毒性反应及处理

小儿白血病主要的治疗方法是化疗,由于化疗方法的改进,使小儿急性白血病的治疗效果明显提高,尤其是小儿急性淋巴细胞性白血病。同时不可忽视的是,随着化疗药物的不断增多,与化疗药物相关的并发症也不断涌现,除由骨髓抑制所致的最常见的感染并发症外,还有一些其他常见且严重的化疗药物所致的毒性反应,特别是心脏损害,主要见于蒽环类药物;肝脏毒性,主要由甲氨蝶呤引起;肾脏毒性主要由环磷酰胺所致,这些毒性反应如未予充分重视,亦可导致小儿白血病治疗的失败。     

对儿童白血病化疗的再认识

公元19世纪人类开始认识白血病.急性白血病(AL)是儿童期最常见的恶性肿瘤,约70%～80%为急性淋巴细胞白血病(ALL),20%～30%为急性髓性白血病(AML).20世纪70年代报道长生存的ALL仅为3%～5%,大部分病情迅速进展而死亡.随着近30年医学的进步,儿童白血病的治疗有了突破性的进展,通过长期序贯联合化疗,大多数患儿可以获得完全缓解(CR),其中ALL和AML的长期无病生存率分别可以达到70%和40%以上.现就国内外的经验,结合我国国情,对我国儿童白血病的治疗提供几点建议.     

改良四唑盐法快速检测白血病细胞对化疗药物的敏感性

为对白血病患儿实施个体化治疗，用四唑盐法测定了２３例急性白血病患儿肿瘤细胞对化疗药物的敏感性，确定了不同化疗药物药敏阈值，计算了联合化疗方案综合杀伤率，并确定了联合化疗时体内外疗效评定标准。２３例白血病患儿药敏评定结果：药敏总符合率为９１．３％，阳性符合率为９４．７％，阴性符合率为７５．０％，体内、外疗效有较好的一致性（ｒ＝０．７，Ｐ＜０．０５）。结果表明，改良四唑盐法检测白血病细胞对化疗药物的敏感性，具有快速、敏感、简便等优点，有临床应用价值。     

蒽环类药物对白血病细胞的细胞毒作用与活性氧的关系研究进展

蒽环类抗生素用于白血病的治疗已30余年历史,已成为化疗不可缺少的药物之一。近年来研究显示,蒽环类抗生素对白血病细胞的细胞毒作用包括凋亡。而活性氧(reactive oxygen species,ROS)是细胞增殖、分化、成熟及凋亡过程中的重要介质;同时它与细胞耐药、心脏毒性有关。研究其作用机制将更好地了解白血病化疗的机制,更好地指导临床治疗。文章简述了蒽环类药物的作用机制及ROS与蒽环类药物细胞毒作用的关系,以期为临床研究提供参考。     

端粒酶在急性白血病中的研究进展

端粒酶实质上是一种逆转录酶,能以自身RNA为模板,合成（TTAGGG）,重复序列,维持肿瘤细胞端粒粒的长度,使其成为永生细胞,具有无限增殖能力,在肿瘤形成和发展中起重要作用,本文重点讨论端粒酶与急性白血病临床特征的关系,研究发现端粒酶活性水平与急性白血病的高危因素和预后密切相关,检测端粒酶活性水平有利于监测病情的变化,指导制定合理的化疗方案。     

罗伊适应模式在儿童急性白血病大剂量化疗期护理中的应用

目的探索罗伊适应模式在急性白血病患儿大剂量化疗期间护理中的应用效果。方法将90例急性白血病患儿随机分为观察组和对照组。对照组45例给予白血病常规护理,观察组45例应用罗伊适应模式实施整体护理。寻找大剂量化疗期间的常见刺激源,并采取护理措施,以控制刺激强度,增强患儿适应性。结果观察组焦虑分值为32.02±4.58,对照组焦虑分值为46.02±11.28,对照组焦虑分值显著高于观察组(P<0.01)。两组患儿在大剂量化疗期间胃肠道反应、肝肾功能损害、出血症状、感染发生率等比较差异均有统计学意义(P<0.05)。结论应用罗伊适应模式对患儿进行整体护理,能使患儿维持更好的状态并减轻大剂量化疗的毒副作用。     

儿童急性白血病化疗合并真菌感染探讨

目的探讨儿童急性白血病化疗合并真菌感染的因素及其感染病原学特点。方法白血病并发真菌感染按EORTC诊断标准。分析真菌感染率、感染部位、感染相关危险因素、病原菌特点。结果共17例白血病患儿21次并发真菌感染,急性淋巴细胞性白血病(ALL)13例,急性非淋巴细胞性白血病(AML)4例;合并真菌感染率为27.6%。感染部位主要位于上呼吸道(61.9%)。病原菌培养均示浅表真菌,如白色念珠菌、酵母样菌。化疗阶段是白血病患儿合并真菌感染的重要因素(P<0.05),免疫功能和中性粒细胞绝对值在临床上亦是主要的影响因素。结论白血病患儿合并真菌感染与疾病本身、机体免疫功能低下、中性粒细胞绝对值和化疗阶段相关。因此,免疫支持、早期诊断、及时治疗颇为重要。     

大剂量化疗治疗急性白血病：附32例报告

本文报告应用大齐量MTX、L-ASP及Ara-c防治髓外白血病。大剂量MTX 1g/m~2治疗急性淋巴细胞白血病(ALL)缓解期24例,经5年观察存活3年以上者无脑白及睾白发生,最长已存活60月。8例急性粒细胞白血病(ANLL)病人缓解期应用高剂量Ara-c 2g/m~2/次q12h,4天总量16g/m~2,共5个疗程,持续缓解期2年以上者37.5%,最长已存活84月。各组毒性反应均为可逆。     

活性氧在新生儿持续性肺动脉高压中的作用

<正>新生儿持续性肺动脉高压(persistent pu1monary hypertension of the newborn,PPHN)是指生后肺血管阻力持续性增高,肺动脉压超过体循环动脉压使由胎儿型循环过渡至正常"成人"型循环发生障碍,导     

褪黑素对哮喘大鼠肺组织活性氧产生的影响(英文)

目的　支气管哮喘是慢性气道炎症性疾病 ,肺组织活性氧产生可以导致气道炎症 ,本研究目的探讨褪黑素 (MT)对哮喘模型大鼠肺组织活性氧 (ROS)生成以及气道炎症的影响。方法　将 2 4只大鼠随机分为 3组 :哮喘组 (n=8) :用 10 %鸡卵白蛋白 (OVA) 1ml、氢氧化铝凝胶 10 0mg无菌腹腔注入 ,2周后用 1%OVA超声雾化吸入 2 0min ,连续激发 1周致其哮喘发作 ;MT组 (n =8) :模型制作同哮喘组 ,在每次激发前 30min腹腔注入MT 10mg/kg ;对照组 (n =8) :以生理盐水代替OVA吸入。每组分别于最后一次激发后 6h测定气道反应性 ;取支气管肺泡灌洗液 (BALF)进行白细胞计数、分类 ;取肺组织进行活性氧产量测定。结果　MT组大鼠气道反应性及BALF中炎性细胞数明显低于哮喘组 ,差异有显著性 (P <0 .0 5 )。肺组织活性氧产量在哮喘组、MT组及对照组分别为 (114 .8± 11.3)U/mgprot、(95 .2± 5 .9)U/mgprot及 (87.5± 7.4 )U/mgprot,哮喘组高于其它两组 ,差异均有显著性 (P <0 .0 5 )。结论　哮喘组大鼠肺组织活性氧产量增加。MT干预可以降低肺组织活性氧产生 ,降低气道炎症和气道高反应性 ,这可能是其治疗哮喘的保护机制。     

The ability of neonatal and maternal erythrocytes to produce reactive oxygen species in response to oxidative stress

The ability of neonatal and maternal erythrocytes to produce reactive oxygen species (ROS) in response to oxidative stress was investigated using the chemiluminescence probe Cypridina luciferin analogue. The chemiluminescence probe, based on 2-methyl-6-[p-methoxyphenyl]-3,7-dihydro-imidazo[1,2-alpha]pyrazin-3-one (MCLA), is highly specific and sensitive to superoxide anion (O(2)(-)) and singlet oxygen (1O(2)). Blood from 11 mothers who experienced no complications and their healthy full-term newborns was collected and heparinized. MCLA was put into the washed erythrocytes suspension, and phenylhydrazine (PH) was added to cause oxidative stress. Chemiluminescence was measured using an Argus 50 image processing system. It was found that erythrocytes in neonatal blood had a 2.0-fold greater maximum chemiluminescence than did those in maternal blood. There was no change in the emission after the addition of NaN(3), but there was complete suppression with superoxide dismutase (SOD), demonstrating that these were O(2)(-).The present results demonstrated that neonatal erythrocytes produce about twice as much O(2)(-) as do adult erythrocytes in response to oxidative stress. With this method, it is very simple to measure the amount of O(2)(-) produced in erythrocytes and the rate at which they are produced. This method may therefore be very useful for determining the effects of antioxidants.     

Human hepatic mitochondria generate reactive oxygen species and undergo the permeability transition in response to hydrophobic bile acids

OBJECTIVES: Hydrophobic bile acids accumulate in the liver during cholestasis and are believed to cause hepatocellular necrosis and apoptosis in part through induction of the mitochondrial permeability transition (MPT) and the mitochondrial generation of oxidative stress. The purpose of this study was to determine if human hepatic mitochondria respond to bile acids in this manner. METHODS: The MPT was measured spectrophotometrically and morphologically in normal human liver mitochondria exposed to glycochenodeoxycholic acid (GCDC) with and without cyclosporin A, an inhibitor of the MPT, antioxidants, and tauroursodeoxycholic acid (TUDC). Hydroperoxide generation was measured by dichlorofluorescein fluorescence. Cytochrome c and apoptosis-inducing factor were assessed by immunoblotting. RESULTS: GCDC induced the MPT in a dose-dependent manner, which was inhibited by cyclosporin A, alpha-tocopherol, beta-carotene, idebenone, and TUDC. GCDC stimulated reactive oxygen species generation and release of cytochrome c and apoptosis-inducing factor, which were significantly inhibited by the antioxidants, cyclosporin A, and TUDC. CONCLUSIONS: Mitochondrial pathways of cell death are stimulated in human hepatic mitochondria exposed to GCDC consistent with the role of mitochondrial dysfunction in the pathogenesis of cholestatic liver injury. These results parallel those reported in rodents, supporting the extrapolation of mechanistic studies of bile acid toxicity from rodent to humans.