Mechanism of Arsenic Trioxide Inhibiting Angiogenesis in Multiple Myeloma

Duringthelast decade,the efficacy of arsenic tri-oxide(As2O3)in both newly diagnosed and relapsedpatients with acute promyelocytic leukemia(APL)hasbeen established.And now,As2O3is used with otheragentsintreating patients with relapsed and refractorymultiple myeloma(MM)in clinical practice[1].Theinitial researches demonstratedthat As2O3couldinhibitproliferation andinduce apoptosisin MMcellsin vitroandin vivo[2,3].In addition to affecting tumorgrowth,As2O3has been showntoinhibit angiogenes…     

砷致癌动物模型研究现状

人类流行病学资料显示,长期暴露于砷化合物可以导致人类皮肤、肺、膀胱、肝和肾脏的癌症。近来报道指出,砷在小鼠和大鼠的相应器官也可诱发促癌或完全致癌作用,给予p53+/-和K6/ODC转基因小鼠无机砷的甲基化代谢产物二甲基胂酸(DMA)或亚砷酸盐,对转基因小鼠的皮肤或膀胱有一定程度的致癌、联合致癌或促癌作用。由于到目前为止尚无无机砷化合物致癌的动物模型,致使其致癌机制的研究一直滞后,所以大量研究人员致力于野生型和转基因动物的砷致癌动物模型研究,本文就这一方面的研究进展做一综述。     

猪肾中砷的氢化物发生原子荧光测定法

目的研究氢化物发生—原子荧光法测定猪肾中砷的适宜条件。方法试验酸介质和还原剂用量对测定砷的影响;选择仪器的最佳工作条件及氢化物发生条件;试验样品中常见元素对砷测定的干扰情况及消除方法。结果在测定条件下,砷的线性范围为0~200μg/L,相关系数达0.999 3以上;检出限为0.14μg/L,回收率在95.5%~101.0%之间,相对标准差(n=7)小于2.7%。结论该试验选用5.0%HCl为介质;样品测定原子化观察高度8 mm;5%硫脲 5%抗坏血酸混合溶液掩弊干扰效果最好。在该工作条件下测定猪肾中的砷,方法灵敏度高,准确度、精密度好。     

三氧化二砷诱导尤文肉瘤细胞凋亡及对EWS—FLil融合蛋白的影响

目的：探讨三氧化二砷（Arsenic trioxide，As2O3）诱导尤文肉瘤细胞凋亡及对融合蛋白EWS—FLi1表达的影响，．方法：应用噻唑蓝（MTF）法、形态学观察、原位末端标记法（TUNEL）、流式细胞术（FCM）观察As2O3对体外生长的尤文肉瘤RD—ES细胞系生物行为的影响：应用半定量RT—PCR测定应用As2O3前后c—mye基因mRNA水平的变化；应用免疫细胞化学及固定化蛋白印迹法（Western blot）观察用药前后EWS—FLi1融合蛋白表达水平的变化、结果：As2O3对体外生长的RD—ES细胞系具有明显抑制作用，并可诱导细胞凋亡、c-mye基因mRNA表达水平和EWS—FLil融合蛋白表达量随As2O3作用时间延长逐渐降低结论：常规治疗浓度的As2O3对体外生长的尤文肉瘤细胞具有明显的杀伤作用，其作用机制与改变线粒体膜通透性和抑制EWS—Flil融合蛋白、降低c一myc基因表达有关。     

The Synergistic Inhibitory Effect of STI571 in Combination with Arsenic Trioxide (As2O3) on Multidrug-Resistant Leukemic Cells

OBJECTIVE To study the synergistic effect of STI571, an inhibitor of tyrosine kinase, in combination with arsenic trioxide As2O3 on a multidrug-resistant leukemia cell line expressing bcr-abl.METHODS The cytotoxic effect of STI571 alone or in combination with different concentrations of As2O3 on the bcr-abl and mdr1 -positive leukemia cell line, K562-n/VCR, was examined by the MTT method.RESULTS One μmol/L of STI571 alone had no significant cytotoxic effect on K562-n/VCR cells. However the cytotoxic effect increased markedly when combined with As2O3 at concentrations of 10-5, 10-6, 10-7 and 10-8 mol/L. The IC50 of K562-n/VCR cells in As2O3 group was 1.879 μmol/L, with. Upon addition of STI571, the IC50 decreased to 0.155 μmol/L resulting in a synergistic cytotoxic effect on K562-n/VCR ceils that was increased 12.1 times.CONCLUSION A combination of STI571 with As2O3 has a more powerful inhibitory effect on leukemia cells expressing positive bcr-abl and positive mdrl compared to the effect with As2O3 alone.     

As_2O_3诱导MGC803细胞凋亡中TRF1、TRF2蛋白表达及端粒稳定性的作用

目的分析三氧化二砷(As2O3)对人胃癌MGC803细胞端粒重复序列结合因子1、2(TRF1、TRF2)表达及端粒稳定性的影响,探讨As2O3诱导细胞凋亡的机制。方法体外培养MGC803细胞,MTT比色实验分析As2O3对MGC803细胞增殖抑制作用,流式细胞术检测MGC803细胞凋亡,进行染色体端-端融合分析及Westernblot检测TRF1、TRF2蛋白表达。结果MTT法显示As2O3对人胃癌MGC803细胞有明显的抑制作用,且呈时间、剂量依赖关系。流式细胞术检测出现典型的凋亡峰,并随As2O3浓度增加和作用时间延长而增高,对照组未见此改变。染色体端-端融合分析显示5μmol·L-1As2O3处理MGC803细胞48h染色体融和率明显高于对照组。Westernblot分析结果表明TRF1在5μmol·L-1As2O3处理MGC803细胞48h后,表达上升,而TRF2表达下降。结论实验结果提示As2O3通过下调TRF2蛋白表达、上调TRF1蛋白表达及使染色体端-端融合,从而诱导MGC803细胞凋亡。     

砒石对哮喘小鼠气道壁厚度及c-myc与c-sis表达的影响

气道重构是哮喘的主要病理特征之一,平滑肌细胞(SMC)、成纤维细胞(FB)是气道粘膜下的主要结构细胞,具有合成和降解细胞外基质(ECM)的双重功能,其大量增殖引起ECM大量沉积,是引起基底膜增厚、导致气道重构的关键因素.近年来研究发现,c-myc 、 c-sis与SMC、FB增殖密切相关,三氧化二砷能抑制哮喘豚鼠的气道炎症.本研究通过建立小鼠哮喘模型,探讨c-myc、c-sis在哮喘气道重构中的作用及砒石对它们的影响,进一步探讨砒石治疗哮喘的可能机制,为哮喘的防治开辟新途径提供理论依据.     

广东地产中药中砷含量的测定

本文采用Ag- DDC分光光度法和新银盐法对广东地产13种中药材的砷含量进行测定,参考相关的限量标准,了解广东地产中药材砷的含量情况。结果发现石菖蒲的砷含量远远高于各项限量标准,其余12种中药材砷的含量较低。     

In vivo percutaneous absorption of arsenic from water and CCA-treated wood residue.

This study was conducted to evaluate the dermal absorption of arsenic from residues present on the surface of wood preserved with chromated copper arsenate (CCA). The research reported herein used methods parallel to those of earlier research on the dermal absorption of radiolabeled arsenic (R. C. Wester et al., 1993, Fund. Appl. Toxicol. 20, 336-340), with modifications to allow use of environmental matrices that are not radiolabeled. These modifications include the surface area of application and dietary intake of arsenic, thus maximizing the potential for detection of dermally absorbed arsenic in exposed animals above diet-associated background levels of exposure. Two forms of arsenic were administered in this work. The first, arsenic in solution, was applied to the skin of monkeys to calibrate the model against prior absorption research and to serve as the basis of comparison for absorption of arsenic from CCA-treated wood residues. The second substrate was residue that resides on the surface of CCA-treated wood. Results from this research indicate that this study methodology can be used to evaluate dermally absorbed arsenic without the use of a radiolabel. Urinary excretion of arsenic above background levels can be measured following application of soluble arsenic, and absorption rates (0.6-4.4% absorption) are consistent with prior research using the more sensitive, radiolabeled technique. Additionally, the results show that arsenic is poorly absorbed from CCA-treated wood residues (i.e., does not result in urinary arsenic excretion above background levels).     

原子荧光光谱法测定乌梅饮片中微量砷、汞的含量

目的:测定净乌梅和乌梅炭中微量砷、汞的含量.方法:采用原子荧光光谱法.结果:乌梅中砷的含量分别为0.0597～1.0001mg·g-1,汞的含量为0.0198～0.0300mg·g-1.结论:本方法操作简便,定量准确.