淫羊藿苷对急性早幼粒白血病细胞体内外效应的研究

目的 :探讨淫羊藿苷 (ICA)对急性早幼粒白血病细胞的诱导分化作用。方法 :采用ICA与全反式维甲酸 (ATRA)对比试验 ,观察ICA在体外及小鼠体内对白血病细胞增殖分化的影响。结果 :ICA在体内外对白血病细胞均有较明显的诱导分化和抑制增殖作用 ,且与ATRA合用可产生明显的协同效应。结论 :ICA具有明显的抗白血病细胞作用     

维甲酸和桂皮酸诱导HL—60细胞分化的研究

目的 探讨维甲酸和桂皮酸联合对人早幼粒白血病细胞（HL－60）诱导分化作用。方法 用1μmol/L全反式维甲酸（ATRA）和2．5mmol/L桂皮酸单独和联合处理HL－60细胞后,观察细胞形态的改变,进行细胞增殖速度、硝基四氮唑蓝（NBT）还原反应、过氧化酶染色的测定。结果 ATRA和桂皮酸都能使HL－60细胞形态向成熟粒细胞转变,两者对HL－60细胞增殖都有明显抑制作用,都能使细胞的BNT还原反应显著增强（P＜0．01）。前者强于后者。过氧化酶染色两者均为弱阳性或阴性。两者联合作用能使分化作用增强,但未显示相加效应。结论 ATRA和桂皮酸都具有诱导HL－60细胞分化作用,前者优于后者,两者联合分化作用增强。     

淫羊藿苷对急性早幼粒白血病细胞体内外效应的研究

目的：探讨淫羊藿苷（ICA）对急性早幼粒白血病细胞的诱导分化作用。方法：采用ICA与全反式维甲酸（ATRA）对比试验,观察ICA在体外及小鼠体内对白血病细胞增殖分化的影响。结果：ICA在体内外对白血病细胞均有较明显的诱导分化和抑制增殖作用。且与ATRA合用可产生明显的协同效应。结论：ICA具有明显的抗白血病细胞作用。     

自噬在急性早幼粒细胞白血病中的研究进展

急性早幼粒细胞白血病（APL）具有特征性的t（15;17）（q22;q21）染色体易位,其表达PML-RARα融合蛋白。全反式维甲酸（ATRA）和三氧化二砷（As2O3）诱导早幼粒白血病细胞分化或凋亡,使APL成为第一种可以治愈的白血病。自噬是维持细胞稳态的重要代谢方式之一,最近有研究显示自噬在ATRA／As2O3诱导治疗中发挥重要作用,而且还可能影响APL对药物诱导凋亡作用的敏感性。因此,今后靶向自噬、调控自噬可能成为APL乃至于其他白血病治疗的一种新手段。对近年来自噬对APL的作用研究进行综述。     

全反式维甲酸诱导分化治疗急性早幼粒白血病

全反式维甲酸诱导分化治疗急性早幼粒白血病孙关林教授（上海瑞金医院）我国首创的全反式维甲酸（ＡＴＲＡ）诱导分化治疗急性早幼粒白血病（Ｍ３、ＡＰＬ）疗法，在临床应用已有十年的历史。由于该疗法具有疗效高，完全缓解（ＣＲ）率达８０％～９０％，不易诱发ＤＩＣ，...     

肿瘤坏死因子对人早幼粒白血病历细胞系HL－60F增殖和分化的影响

肿瘤坏死因子对人早幼粒白血病历细胞系ＨＬ－６０Ｆ增殖和分化的影响朱宁希，卢家祥，顾桂玲浙江中医学院附属医院（杭州·３１０００６）人早幼粒白血病细胞系ＨＬ一６０是目前白血病体外研究常用的实验模型，多种分化诱导剂能诱导ＨＬ一６０细胞向成熟细胞分化［１］。...     

淫羊藿甙对急性早幼粒白血病细胞端粒酶活性的影响

目的：探讨淫羊藿甙（ICA）对急性早幼粒白血病细胞端粒酶活性的影响。方法：采用ICA与全反式维甲酸（AT-RA）对比试验。观察ICA对白血病细胞端粒酶活性及增殖分化的影响。结果：ICA可明显抑制端粒酶活性，对白血病细胞均有较明显的诱导分化和抑制增殖作用。且与ATRA合用可产生明显的协同效应。结论：ICA具有抑制急性早幼粒白血病细胞端粒酶活性的作用。     

维甲酸和维生素C对HL-60细胞诱导分化的研究

[目的]探讨全反式维甲酸(ATRT)和维生素C(V鄄C)对人早幼粒白血病细胞(HL鄄60)的分化作用。[方法]用1μmol/LATRT和0.5mmol/LV鄄C单独和联合处理HL鄄60细胞后,观察细胞形态改变,测定细胞增殖速度、硝基四氮唑蓝(NBT)还原反应、过氧化酶染色反应。[结果]两者都能使HL鄄60细胞形态向成熟粒细胞转变,对细胞增殖有明显的抑制作用,前者强后者弱;维甲酸使细胞的NBT反应显著增强(P<0.01),过氧化酶染色为弱阳性或阴性;V鄄C对HL鄄60细胞也有NBT反应和染色反应,但改变不明显(P<0.05),两者联合作用,分化作用增强。[结论]维甲酸有很强的诱导HL鄄60细胞分化的作用,V鄄C的分化作用不明显,但有增强维甲酸分化的作用。     

亚硒酸钠和维甲酸联合对HL－60细胞生长、分化的影响

 以人早幼粒白血病细胞（HL－60）为实验对象，观察了亚硒酸钠和维甲酸联合作用对其生长、分化的影响。结果表明：5.8μmol/L亚硒酸钠和0.1μmol/L维甲酸联合可显著抑制细胞生长，且细胞毒性并无增加，强于两者的单独作用。而且可明显诱导细胞向粒系细胞分化，在处理5天后有72%的细胞进行分化。单用0.1μmol/L维甲酸只有39%的细胞分化成熟。NBT还原实验表现出类似结果。     

亚硒酸钠和维甲酸联合对HL－60细胞生长、分化的影响

以人早幼粒白血病细胞（ＨＬ－６０）为实验对象，观察了亚硒酸钠和维甲酸联合作用对其生长、分化的影响。结果表明：５．８μｍｏｌ／Ｌ亚硒酸钠和０．１μｍｏｌ／Ｌ维甲酸联合可显著抑制细胞生长，且细胞毒性并无增加，强于两者的单独作用。而且可明显诱导细胞向粒系细胞分化，在处理５天后有７２％的细胞进行分化。单用０．１μｍｏｌ／Ｌ维甲酸只有３９％的细胞分化成熟。ＮＢＴ还原实验表现出类似结果。     

全反式维甲酸联合干扰素α-2a治疗膀胱癌

目的 观察联合应用全反式维甲酸(ATRA)和干扰素d-2a(IFN-α-2a)治疗大鼠膀胱肿瘤的疗效并探讨其机制.方法 建立大鼠膀胱肿瘤模型50只,44只存活的大鼠随机分为A(11只)、B(11只)、C(11只)、D(11只)4组,膀胱内分别灌注DMSO、IFN-α-2a、ATRA和ATRA+IFN-α-2a治疗.显微镜观察病理分期及分级,流式细胞术(FCM)检测肿瘤细胞的凋亡和细胞周期.结果 D组大鼠体重(277.4±18.5)g高于其他3组,膀胱重量(0.19±0.05)g低于其余3组,并且D组病理分期和分级均有显著降低.D组肿瘤细胞凋亡率(13.43±3.06)%较其他三组明显增加,而增生指数(19.95±4.17)%则明显降低.结论 ATRA和IFN-α-2a联合应用能显著促进肿瘤细胞凋亡,对膀胱肿瘤有更好的疗效.     

全反式维甲酸联合干扰素治疗膀胱癌

 目的　观察联合应用全反式维甲酸（ATRA）和干扰素α-2a（IFN-α-2a）治疗大鼠膀胱肿瘤的疗效并探讨其机制。方法　建立大鼠膀胱肿瘤模型50只，44只存活的大鼠随机分为A（11只）、B（11只）、C（11只）、D（11只）4组，膀胱内分别灌注DMSO、IFN-α-2a、ATRA和ATRA+IFN-α-2a治疗。显微镜观察病理分期及分级，流式细胞术（FCM）检测肿瘤细胞的凋亡和细胞周期。结果　D组大鼠体重（277.4±18.5）g高于其他3组，膀胱重量（0.19±0.05）g低于其余3组，并且D组病理分期和分级均有显著降低。D组肿瘤细胞凋亡率（13.43±3.06）％较其他三组明显增加，而增生指数（19.95±4.17）％则明显降低。结论　ATRA和IFN-α-2a联合应用能显著促进肿瘤细胞凋亡，对膀胱肿瘤有更好的疗效。     

Bryostatin-1 and 1alpha,25-dihydroxyvitamin D3 synergistically stimulate the differentiation of NB4 acute promyelocytic leukemia cells.

One of the objectives of treatment for patients with acute promyelocytic leukemia (APL) is to induce tumor cell differentiation and block cell proliferation. Acute promyelocytic leukemia cells (NB4) responded to the combination treatment of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] plus phorbol 12-myristate 13-acetate (PMA) and differentiated into monocyte/macrophage-like cells, as well as expressed strong alkaline phosphatase (ALP) activities. Since PMA has limited clinical application due to its tumor-promoting effect, another protein kinase C activator, bryostatin-1, was currently tested for its interaction with 1alpha,25(OH)2D3 to induce NB4 cell differentiation and block cell proliferation. Bryostatin-1 alone, but not 1alpha,25(OH)2D3 alone, significantly inhibited cell proliferation and induced NB4 cell differentiation into monocyte/macrophages; however neither bryostatin-1 nor 1alpha,25(OH)2D3 alone induced ALP expression. Like PMA, bryostatin-1 synergistically interacted with 1alpha,25(OH)2D3 to stimulate ALP expression 30-fold over the control (P < 0.001) and further promote appearance of monocyte/macrophage-like cells. The ALP stimulation was both time- and dose-dependent. Thus, we demonstrate for the first time that the combination of bryostatin-1 and 1alpha,25(OH)2D3 strongly affect NB4 cell differentiation and proliferation. Therefore, this proposed combination treatment may be an alternatively potential therapeutic regimen for APL patients and assay of ALP may be a more sensitive and facile way to monitor the possible remission of APL patients.     

早幼粒细胞白血病锌指基因在肿瘤和免疫系统中的作用及研究进展

早幼粒细胞白血病锌指基因（promyelocytic leukemia zinc finger gene,PLZF）所编码的蛋白,作为一种转录因子,参与多种生物过程的调控,包括细胞的增殖、分化、凋亡、干细胞自我更新、器官和先天性免疫细胞发育等。近年来研究表明,PLZF不仅与血液系统肿瘤的发生发展相关,在多种实体肿瘤中也存在表达失调,且往往提示临床分期、肿瘤转移、预后等。除此之外,我们还发现PLZF的免疫调节作用,这或将成为抗肿瘤免疫治疗的新思路。     

Tumor necrosis factor-related apoptosis-inducing ligand-mediated proliferation of tumor cells with receptor-proximal apoptosis defects

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might represent a future cytotoxic drug to treat cancer as it induces apoptosis in tumor cells without toxicity in animal trials. We recently described that in contrast to apoptosis, TRAIL mediates tumor cell survival and proliferation in certain tumor cells. Here we studied the effect of TRAIL on 18 cell lines and 53 primary leukemia cells and classified these tumor cells into four groups: TRAIL, anti-DR4 or anti-DR5 induced apoptosis in group A cells, whereas they had no effect on group 0 cells and mediated proliferation in group P cells. To our surprise, TRAIL induced simultaneous apoptosis and proliferation in group AP cells. More than 20% of all cells tested belonged to group P and showed TRAIL-mediated proliferation even in the presence of certain cytotoxic drugs but not inhibitors of nuclear factor-kappaB. Transfection with B-cell leukemia/lymphoma protein 2 transformed group A cells into group 0 cells, whereas transfection with Fas-associated polypeptide with death domain (FADD)-like interleukin-1-converting enzyme-inhibitory protein (FLIP) transformed them into group AP cells. Loss of caspase-8 or transfection of dominant-negative FADD transformed group A cells into group P cells. Taken together, our data suggest that proliferation is a frequent effect of TRAIL on tumor cells, which is related to receptor-proximal apoptosis defects at the level of the death-inducing signaling complex and should be prevented during antitumor therapy with TRAIL.     

Granulocyte-colony Stimulating Factor and Retinoic Acid Cooperatively Induce Granulocytic Differentiation of Acute Promyelocytic Leukemia Cells in vitro

The interaction of granulocyte-colony stimulating factor (G-CSF) and retinoic acid (RA) in proliferation and differentiation of acute promyelocytic leukemia (APL) cells was examined. G-CSF stimulated proliferation of APL cells at concentrations of 0.1 to 50 ng/ml in a dose dependent manner. More than 10⁻⁸ M RA induced granulocytic differentiation of APL cells. Although G-CSF induced lysozyme activities in APL cells, it alone did not induce terminal differentiation of APL cells. G-CSF significantly enhanced the RA-induced granulocytic differentiation of APL cells in vitro. Enhancement by G-CSF was not due to the prolongation of survival of RA-induced differentiated cells, but the differentiation-inducing effects of G-CSF might be evident only in the presence of RA. Since G-CSF has a potential to induce the granulocytic differentiation of myeloid leukemia cells, G-CSF in combination with RA may be applicable in differentiation induction therapy for some types of myeloid leukemia.     

大蒜素抑制人急性早幼粒白血病细胞生长的体外实验

本实验采用体外直接杀伤测定法，荧光偏振技术，ＭＴＴ比色分析法，ＤＮＡ合成的［３Ｈ］－ＴｄＲ掺入法，微量量热法五种测定技术从细胞膜流动性改变、线粒体功能，ＤＮＡ合成速率、细胞总代谢率变化等细胞和分子生物学方面的变化研究大蒜素对ＨＬ－６０细胞的作用，结果表明，大蒜对对ＨＬ－６０细胞的增殖有抑制作用，高浓度（＞３０ｍｇ／Ｌ）时还有较明显的直接杀伤作用。