CAG方案治疗骨髓增生异常综合征RAEB的疗效观察

目的:探讨CAG方案治疗骨髓增生异常综合征—难治性贫血伴原始细胞增多(MDS-RAEB)的疗效。方法:11例患者使用CAG方案:阿糖胞苷(Ara-C)10mg.m-212h-1皮下注射,第1~14d;阿柔比星7mg.m-2d-1,静脉滴注,第1~8d,G-CSF200μg.m-2d-1,皮下注射,两个疗程后作评定。结果:11例患者中,CR6例,PR3例,NR2例,CR率为54.5%,有效率81.8%,全组未见明显毒副反应。结论:CAG方案治疗MDS疗效肯定,缓解率较高,可作为部分MDS的治疗手段。     

Antitumor Activity and Pharmacology of 1-β-D-Arabinofuranosylcytosine-5'-stearylphosphate: An Orally Active Derivative of 1-β-D-Arabinofuranosylcytosine

The antitumor activity of l-β-D-arabinofuranosylcytosine-5'-alkylphosphates (CnPCAs) against L1210 leukemia in mice after oral administration was demonstrated. The optimum length of the alkyl group on the phosphate moiety of CnPCA for exhibiting a high antitumor activity was found to be between tetradecyl (C14) and tricosyl (C23). The most active alkyl derivative in this system was found to be l-β-D-arabinofuranosylcytosine-5'-stearylphosphate (C18PCA). The optimum and minimum effective doses of C18PCA were 100 and 6,25 mg/kg/day (q1d, day 1 to day 5), respectively. The maximum T/C% of C18PCA was approximately 220. The antitumor activity of C18PCA was not greatly dependent on the treatment schedule and route. Plasma concentration of 1-β-D-arabinofurano-sylcytosine (ara-C) remained in the range of 0.4 to 0.75 μmol/ml for 24 h after oral administration of 100 mgAg (170 μmol/kg) of C18PCA. These results indicate that C18PCA administered per orally is absorbed intact through the gastrointestinal tract and ara-C is released for a long period of time. C18PCA is regarded as an orally active depot form of ara-C     

Consolidation therapy: What should be the standard of care?

Adults 18-60 years old with acute myelogenous leukemia (AML) should undergo some form of postremission therapy, however, how much and what kinds of postremission chemotherapy remain unclear. In contrast, for older patients more than one cycle of chemotherapy postremission does not appear justified except perhaps in those rare patients with favorable cytogenetics who are young enough to tolerate standard therapy and in whom there is still an option for cure. Routine postremission therapy is not justifiable for those with unfavorable cytogenetics. However, the median age of AML patients approaches 70 years; this is a group of patients who often reach minimal disease, but with a median disease-free survival of only 4 to 5 months, regardless of their cytogenetics, and are therefore an ideal patient group for clinical studies. Older patients have limited tolerance for intensive regimens, although relatively nontoxic agents exist that can be explored. The issue of maintenance remains open.     

JWA基因在HL-60细胞定向分化中的表达及意义

为了研究JWA基因在HL-60细胞定向分化中的表达规律,探讨其在白血病细胞分化和凋亡中的意义及可能的作用机制,应用FCM检测HL-60细胞经ATRA（10^-6 mol/L）、Ara-C（10 ng/ml）、TPA（10^-8 mol/L）作用后2、4、6、8天CD13、CD14、CD15、CD11b改变及细胞周期变化;应用半定量RT-PCR及蛋白印迹技术检测JWA基因在HL-60细胞定向分化中的表达趋势以及相关凋亡因子Bcl-2、HSP27和HSP70的表达.结果表明：经上述药物分别处理HL-60细胞后,不同时段FCM相关指标检测结果证明其分别向粒、单核、巨噬细胞样分化.JWA基因表达呈时间依赖性升高;Bcl-2则呈时间依赖性下降;HSP70在ATRA及TPA组与JWA表达呈正相关,与Bcl-2呈负相关,而各组HSP27并无表达.ATRA处理HL-60细胞后JWA基因表达趋势与原代细胞相反,且不需要ATRA诱导分化作为前提.分别以Ara-C 10 ng/ml和Ara-C 20 ng/ml处理HL-60细胞后,JWA基因的表达呈反向变化,即前者呈时间依赖性增加,而后者则下降.结论：JWA基因在实现ATRA及TPA诱导白血病细胞分化和凋亡中可能具有双重调节作用;JWA基因表达的高低与Ara-C诱导分化作用及细胞毒作用有关;HL-60细胞与原代白血病细胞在诱导分化机制方面可能不尽相同.     

硼替佐米联合低浓度阿糖胞苷诱导U937细胞凋亡的研究

本研究探讨蛋白酶体抑制剂硼替佐米联合低浓度阿糖胞苷(Ara-C)对U937细胞株的作用及机制。通过细胞计数,细胞形态学检查,流式细胞术和Western blot方法检测硼替佐米(10 nmol/L)和(或)Ara-C(50 nmol/L)处理前后U937细胞的增殖抑制和凋亡及其机制。结果显示,硼替佐米和Ara-C单药均能抑制U937细胞增殖,两药联合的抑制作用更加明显,细胞增殖抑制率在24和48 h分别达(55.00±2.81)%和(70.02±3.33)%;硼替佐米联合低浓度Ara-C能协同诱导U937细胞凋亡,促使线粒体跨膜电位下降,阳性细胞率达(38.70±1.54)%。两药联合应用还能协同诱导caspase-9,-8,-3的活化。结论:硼替佐米联合低浓度Ara-C主要通过线粒体途径、可能还通过死亡受体途径诱导U937细胞凋亡。     

Functional implications of hypothalamic neurogenesis in the adult mammalian brain

Adult neurogenesis represents a striking example of structural plasticity in the mature brain. Research on adult mammalian neurogenesis today focuses almost exclusively on two areas: the subgranular zone (SGZ) in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ) of the lateral ventricles. Numerous studies, however, have also reported adult neurogenesis in the hypothalamus, a brain structure that serves as a central homeostatic regulator of numerous physiological and behavioral functions, such as feeding, metabolism, body temperature, thirst, fatigue, aggression, sleep, circadian rhythms, and sexual behavior. Recent studies on hypothalamic neurogenesis have identified a progenitor population within a dedicated hypothalamic neurogenic zone. Furthermore, adult born hypothalamic neurons appear to play a role in the regulation of metabolism, weight, and energy balance. It remains to be seen what other functional roles adult hypothalamic neurogenesis may play. This review summarizes studies on the identification and characterization of neural stem/progenitor cells in the mammalian hypothalamus, in what contexts these stem/progenitor cells engage in neurogenesis, and potential functions of postnatally generated hypothalamic neurons.     

利血康抗阿糖胞苷性血小板减少症作用的实验研究

目的 研究利血康颗粒(三七、白及、藕节等)抗小鼠阿糖胞苷性血小板减少症模型的作用.方法 采用小鼠阿糖胞苷性血小板减少症模型,同时灌服利血康颗粒3种剂量2.25、1.13、0.56g/kg(折合生药9、4.5、2.25g/kg,ig)治疗8d,观察药物对该动物模型凝血时间、外周血血小板(Bpc)数、骨髓巨核细胞数和骨髓DNA的影响.结果 利血康颗粒高、中剂量可明显缩短阿糖胞苷性血小板减少症模型小鼠的凝血时间、升高外周血Bpc数、骨髓巨核细胞数和骨髓DNA.结论 利血康颗粒对小鼠阿糖胞苷性继发性血小板减少症模型具有拮抗作用,该作用与其促进骨髓造血干细胞尤其是骨髓巨核细胞的分化增殖,减轻骨髓抑制有关.     

FLAG方案和IA方案对P-gp阳性和阴性急性髓细胞白血病细胞的作用

 目的　探讨FLAG和IA方案对P-gp阳性和阴性急性髓细胞白血病（AML）细胞增生抑制作用的优劣及其机制。方法　流式细胞仪检测K562和K562／A02细胞的P-gp 表达,MTT法检测FLAG和IA方案对K562和K562／A02细胞的增生抑制作用,高效液相色谱法检测细胞内Ara-CTP、Ara-C水平,实时定量PCR检测细胞hENT1基因表达。结果　K562 和K562／A02细胞的P-gp阳性率分别为（1.32±0.24）%和（97.66±3.77）%,两种化疗方案对细胞的P-gp表达无影响。FLAG方案对K562细胞的增生抑制作用较IA方案差[（73.17±13.20）%对（84.41±9.33）%,P <0.05],而对K562／A02细胞的增生抑制作用优于IA方案[（70.55±11.32）%对（48.46±12.81）%,P <0.01]。FLAG方案作用时AML细胞内Ara-CTP、Ara-C水平及人平衡核苷载体（hENT1）基因表达均较IA方案作用时升高（P <0.05）。结论　P-gp阳性AML细胞对FLAG方案较IA方案更敏感。氟达拉滨对Ara-C的生化调节可能是其主要机制。     

常规剂量阿糖胞苷在老年急性髓细胞白血病中的应用

目的：根据老年急性髓细胞白血病(AML)的临床特点，评估常规剂量阿糖胞苷(Ara-C)作为诱导缓解治疗方案的疗效。方法：对25例老年AML患者以常规剂量Ara-C(200mg／m^2)静脉输注，1次，d，连用7天。获完全缓解后按原方案最多再进行3个疗程的巩固，维持治疗。结果：诱导化疗阶段完全缓解12例(48％)，早期死亡2例(8％)，化疗诱导期死亡4例(16％)，中位生存期6．1个月，而不良反应以感染、出血为主。结论：老年AML具有独特的生物学及临床特征，适于常规剂量Ara-C方案诱导化疗。