山姜素对急性重症胰腺炎大鼠肺损伤中水通道蛋白-1表达的影响

目的探讨山姜素对急性重症胰腺炎(SAP)肺损伤的保护作用是否与水通道蛋白(AQP)-1表达相关。方法选取60只雄性SD大鼠,随机分为正常对照组(Control组),假手术组(Sham组)、模型组(SAP组)、山姜素治疗组(Alpinetin组)每组15只。以逆行注入15 g/L熊去氧胆酸钠(1 ml/kg)30 s注射制作SAP模型。各组均于造模8 h后剖杀,提取肺组织。检测肺组织髓过氧化物酶(MPO)活性、湿/干重比及对肺脏进行病理学评分;取材测定血清肿瘤坏死因子(TNF)-α含量;RT-PCR检测肺组织AQP-1 mRNA的表达,免疫组化法检测肺组织AQP-1的表达。结果 SAP组与Sham组相比,SAP组肺组织损害程度明显升高(P0.01),血清TNF-α,MPO活性明显增加(P0.05)。AQP-1 mRNA与AQP-1蛋白表达显著下调(P0.05)。Alpinetin组与SAP组相比,Alpinetin组肺干/湿比值、肺组织病理损害程度、血清TNF-α明显降低(P0.05),AQP-1 mRNA和AQP-1蛋白表达则明显升高(P0.05),AQP-1表达水平与TNF-α呈负相关。结论应用山姜素能够对SAP肺损伤起到明显的保护作用,其机制可能与抑制肺组织分泌TNF-α和上调AOP-1水平有关。     

丙酮酸乙酯对急性坏死性胰腺炎大鼠肺损伤的保护作用

目的:观察丙酮酸乙酯(EP)对急性坏死性胰腺炎(ANP)肺损伤大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和肺组织高迁移率族蛋白B1(HMGB1)mRNA表达的影响,探讨丙酮酸乙酯治疗急性坏死性胰腺炎肺损伤的机制.方法:逆行性胰胆管注射50 g/L牛磺胆酸钠制作ANP模型.随机分成3组,对照组、ANP组和EP治疗组(40 mg/kg,每隔6h静脉注射一次).ELISA法检测血清TNF-α和IL-1β水平;半定量逆转录聚合酶链反应(RT-PCR)法检测肺组织HMGB1 mRNA表达,并观察血氧变化及肺组织的病理变化.结果:ANP组血清TNF-α和IL-1β水平在建模后6h达高峰,12h下降,在此两时点治疗组血清TNF-α和IL-1β水平明显低于ANP组(TNF-α:131.6±29.6 ng/L vs 196.3±16.3 ng/L,65.0±16.6 ng/L vs 90.2±20.1 ng/L,P<0.05;IL-1β:194.9±26.8 ng/L vs 223.0±34.8 ng/L,105.2±24.0 ng/L vs 130.4±23.0 ng/L,P<0.05).ANP组大鼠肺组织HMGB1 mRNA表达水平在ANP后12h明显升高,至24h仍维持在高水平.治疗组肺组织HMGB1 mRNA表达水平在各时间点均明显低于ANP组(0.68±0.11 vs 0.88±0.11,0.81±0.11 vs 1.04±0.10,1.08±0.08 vs 1.33±0.15,P<0.05),且同期肺损伤比ANP组轻.治疗组PaO_2均明显高于ANP组.结论:丙酮酸乙酯能显著抑制TNF-α、IL-1β和HMGB1等早晚期炎症因子,改善低氧血症,对ANP肺损伤有明显保护作用.     

脂质体介导核因子-κB诱捕物寡聚脱氧核苷酸对重症急性胰腺炎大鼠胰腺炎症因子mRNA表达和胰腺损伤的影响

目的:探讨脂质体(liposome)介导核因子-κB(nuclear factor κB,NF-κB)诱捕物(decoy)寡聚脱氧核苷酸(ODN)对重症急性胰腺炎大鼠胰腺NF-κB活性及受其调控炎症因子基因mRNA表达和胰腺损伤的影响.方法:除假手术组(n=10)外,其余SD大鼠以牛磺胆酸钠(STC)诱导建立重症急性胰腺炎模型后,分别于建模后1 h静脉注射裸ODN(n=10)、脂质体/decoy ODN复合物(n=10)、脂质体/scrambled ODN复合物(n=10)和生理盐水(n=10),注射4 h应用电泳迁移率变动分析(EMSA)NF-κB的活性,利用逆转录-聚合酶链反应(RT-PCR)法检测胰腺组织ICAM-1,IL-1α,IL-2,TNF-α,VCAM-1 mRNA表达,同时检测血淀粉酶、胰腺组织湿/干重比率和胰腺组织髓过氧化物酶(MPO).结果:EMSA显示,脂质体/decoy ODN复合物组NF-κB活性明显低于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组,均有显著性差异(P＜0.05).RT-PCR结果显示,脂质体/decoy ODN复合物组ICAM-1,IL-1α,IL-2,TNF-α和VCAM-1 mRNA表达低于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组,均有显著性差异(ICAM-1:0.75±0.13 vs 1.39±0.15,1.37±0.16,1.32±0.17,P＜0.05;IL-1α:0.64±0.09 vs 1.34±0.20,1.30±0.14,1.25±0.20,P＜0.05;IL-2:0.23±0.08vs 0.74±0.13,0.71±0.12,0.69±0.14,P＜0.05;TNF-α:0.41±0.13 vs 1.30±0.17,1.26±0.17,1.23±0.20,P＜0.05;VCAM-1:0.21±0.06 vs 0.68±0.13,0.69±0.15,0.63±0.13,P＜0.05).与生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组相比,脂质体/decoy ODN复合物组淀粉酶、胰腺组织湿/干重比率和胰腺组织MPO活性显著性降低(淀粉酶:50931.85±22432.15 nkat/L vs 188024.26±38659.56,188412.68±37988.26,183119.95±33636.23nkat/L,all P＜0.05;湿/干重比率:5.76±0.20 vs 6.77±0.18,6.72±0.18,6.35±0.12,P＜0.05;MPO活性:46.68±3.00 nkat/g vs 99.02±2.50,98.19±2.83,98.52±2.50 nkat/g,P＜0.05).结论:NF-κB decoy ODN可特异性抑制胰腺NF-κB活性及其调控的炎症因子ICAM-1,IL-1α,IL-2,TNF-α和VCAM-1 mRNA的表达,减轻胰腺损害.     

大鼠急性胰腺炎时胰腺腺泡细胞凋亡及Bax,Caspase-8的表达

目的:研究大鼠急性胰腺炎腺泡细胞凋亡情况,凋亡调控基因Bax与凋亡蛋白酶Caspase-8的表达及其同疾病严重程度的关系.方法:胆胰管逆行注入不同浓度去氧胆酸钠方法制备大鼠急性胰腺炎模型,设假手术(SO)组、急性水肿性胰腺炎(AEP)组和急性坏死性胰腺炎(ANP)组.采用TUNEL技术检测胰腺腺泡细胞的凋亡,RT-PCR与免疫组化方法分别分析胰腺组织Bax,Caspase-8 mRNA及蛋白的表达,对胰腺组织进行病理学评分并测定血清淀粉酶及IL-6,TNF-α含量.结果:与SO组比较,AEP与ANP组胰腺组织显示不同程度的病理损害,血清淀粉酶(63 413±6118,1 532 134±17 654 nkat/L vs 15 736±483 nkat/L,P＜0.01)及TNF-α(1.86±0.13,2.97±0.14μg/L vs 0.95±0.08 μg/L,P＜0.01),IL-6 (47.10±7.05,170.10±7.59 ng/L vs 29.20±4.47 ng/L,P＜0.01)浓度显著升高,且ANP组显著高于AEP组(P＜0.05);AEP与ANP组腺泡细胞凋亡指数显著升高(22.09±3.71,6.50±1.58 vs 0.13±0.05,P＜0.01),但ANP组显著低于AEP组(P＜0.05).同时发现,AEP与ANP组胰腺组织Bax (mRNA:1.530±0.501,1.046±0.337;蛋白:453.7±30.5,339.4±26.7)和Caspase-8(mRNA:0.595±0.17,0.505±0.173;蛋白:3606±337,3134±231) mRNA及蛋白表达水平均显著高于SO组(Bax mRNA:0.613±0.244,Bax蛋白:245.2±30.0;Caspase-8mRNA:0.357±0.130,Caspase-8蛋白:2396±266)(P＜0.01),ANP组Bax mRNA及蛋白表达水平显著低于AEP组(1.046±0.337,339.4±26.7 vs 1.530±0.501,453.7±30.5,P＜0.05),ANP组Caspase-8 mRNA及蛋白表达水平低于AEP组,但差异不具有显著性意义.结论:急性胰腺炎时胰腺腺泡细胞发生凋亡伴随凋亡调控基因Bax与凋亡蛋白酶Caspase-8表达增加,并同病情严重程度呈负相关关系.     

乌司他定对急性坏死性胰腺炎大鼠合并肺损伤的影响

目的 探讨乌司他定(UT1)对急性坏死性胰腺炎大鼠(ANP)合并肺损伤时肺内ET-1和NF-κB表达及肺损伤的影响.方法 60只SD大鼠按随机数字法分成假手术组、ANP组和UTI组,各20只.采用胆胰管逆行注射5%牛磺胆酸钠溶液1 ml/kg体重制备ANP模型,假手术组胰管注射等量生理盐水,UT1组在ANP制模成功后即从大鼠尾静脉注射UTI 10 000 U/kg体重.24 h后处死动物,测血清淀粉酶、TNF-α、肺组织湿/干重比,免疫组化法检测肺组织NF-κB和ET-1蛋白表达以及使用TUNEL法检测细胞凋亡.结果 UTI组术后24 h血清淀粉酶、TNF-α和肺湿/干重比分别为(5 648±378)U/L、(89.19±3.54)ng/L和4.55±0.07,较ANP组的(6 799±437)U/L、(183.30±8.18)ng/L和4.89±0.20显著降低(P＜0.05).假手术组末见NF-κB和ET-1表达,未见凋亡细胞.UTI组NF-κB和ET-1阳性表达率分别为(19±3)%和(8±1)%,较ANP组的(25±2)%和(13±1)%显著降低(P＜0.05).UTI组细胞凋亡指数为13.75±1.25,较ANP组的6.90±0.85显著升高(P＜0.05).结论 ANP时肺组织NF-κB和ET-1的高表达可能导致肺损伤.UTI能改善肺微循环,减轻肺炎症性损伤.     

脂质体介导核因子-kappaB诱捕物寡聚脱氧核苷酸对重症急性胰腺炎大鼠胰腺炎症因子mRNA表达和胰腺损伤的影响

目的探讨脂质体(liposome)介导核因子-κB(nuclear factor κB,NF-κB)诱捕物(decoy)寡聚脱氧核苷酸(ODN)对重症急性胰腺炎大鼠胰腺NF-κB活性及受其调控炎症因子基因mRNA表达和胰腺损伤的影响.方法除假手术组(n=10)外,其余SD大鼠以牛磺胆酸钠(STC)诱导建立重症急性胰腺炎模型后,分别于建模后1 h静脉注射裸ODN(n=10)、脂质体/decoy ODN复合物(n=10)、脂质体/scrambled ODN复合物(n=10)和生理盐水(n=10),注射4 h应用电泳迁移率变动分析(EMSA)NF-κB的活性,利用逆转录-聚合酶链反应(RT-PCR)法检测胰腺组织ICAM-1,IL-1α,IL-2,TNF-α,VCAM-1 mRNA表达,同时检测血淀粉酶、胰腺组织湿/干重比率和胰腺组织髓过氧化物酶(MPO).结果EMSA显示,脂质体/decoy ODN复合物组NF-κB活性明显低于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组,均有显著性差异(P＜0.05).RT-PCR结果显示,脂质体/decoy ODN复合物组ICAM-1,IL-1α,IL-2,TNF-α和VCAM-1 mRNA表达低于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组,均有显著性差异(ICAM-10.75±0.13 vs 1.39±0.15,1.37±0.16,1.32±0.17,P＜0.05;IL-1α0.64±0.09 vs 1.34±0.20,1.30±0.14,1.25±0.20,P＜0.05;IL-20.23±0.08vs 0.74±0.13,0.71±0.12,0.69±0.14,P＜0.05;TNF-α0.41±0.13 vs 1.30±0.17,1.26±0.17,1.23±0.20,P＜0.05;VCAM-10.21±0.06 vs 0.68±0.13,0.69±0.15,0.63±0.13,P＜0.05).与生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组相比,脂质体/decoy ODN复合物组淀粉酶、胰腺组织湿/干重比率和胰腺组织MPO活性显著性降低(淀粉酶50931.85±22432.15 nkat/L vs 188024.26±38659.56,188412.68±37988.26,183119.95±33636.23nkat/L,all P＜0.05;湿/干重比率5.76±0.20 vs 6.77±0.18,6.72±0.18,6.35±0.12,P＜0.05;MPO活性46.68±3.00 nkat/g vs 99.02±2.50,98.19±2.83,98.52±2.50 nkat/g,P＜0.05).结论NF-κB decoy ODN可特异性抑制胰腺NF-κB活性及其调控的炎症因子ICAM-1,IL-1α,IL-2,TNF-α和VCAM-1 mRNA的表达,减轻胰腺损害.     

巨噬细胞移动抑制因子在大鼠急性坏死性胰腺炎肺损伤中的作用

目的 检测急性坏死性胰腺炎(severe acute pancreatitis,ANP)大鼠肺组织巨噬细胞移动抑制因子(MIF)mRAN表达及TNF-α含量,探讨它们在ANP肺损伤中的作用机制.方法 40只SD大鼠随机分成对照组及ANP 3、6、12 h组.采用5%牛磺胆酸钠(0.1 ml/100 g体重)胆胰管逆行注射方法制备ANP模型.取血检测血清淀粉酶.取胰腺组织和肺组织行病理学检查,并称重计算其湿/干重比.采用RT-PCR法检测肺组织MIF mRNA表达,放免法测定肺组织TNF-α含量.结果 ANP组血淀粉酶、胰腺和肺组织湿/干重比显著升高,病理损伤随时间延长逐渐加重.ANP 3、6、12 h组肺组织TNF-α含量分别为(0.69±0.07)ng/ml、(1.64±0.10)ng/ml和(0.92±0.11)ng/ml;MIF mRNA表达量分别为1.97±0.09、2.55±0.23、3.29±0.26,均显著高于对照组的(0.19±0.06)ng/ml和1.21±0.34(P值均<0.01).肺组织MIFmRNA表达与肺组织病理损伤、肺湿干重比、TNF-α含量均呈正相关,相关系数分别为r=0.637、r=0.684、r=0.858,P值均<0.01.肺组织TNF-α含量与肺损伤、肺湿/干重比均呈正相关,相关系数分别为r=0.540和r=0.421,P值均<0.01.结论 ANP大鼠肺组织MIFmRNA过表达,TNF-α含量显著增加,它们共同参与肺损伤的发生.     

人参二醇皂苷对重症胰腺炎急性肺损伤时水通道蛋白表达的影响

目的 探讨人参二醇皂苷(panaxadiols,PDS)对急性重症胰腺炎(SAP)急性肺损伤时的水通道蛋白(AQP-1)影响.方法 Wistar大鼠随机分为假手术组(SO组)、SAP组、地塞米松组(DEX组)和PDS组,每组8只.SAP组、DEX组和PDS组大鼠胰管逆行注射5%牛磺酸黄制备大鼠胰腺炎模型;SO组手术操作同其他组,但不向胰管内注射5%牛磺酸钠.制模成功后DEX组腹腔注入DEX,剂量为0.5 mg/100 g;PDS组腹腔注入PDS,剂量为2.5 mg/100 g.模型制作6 h后杀鼠,测定血清淀粉酶、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6),肺脏湿/干重比值;应用RT-PCR测定肺脏AQP-1 mRNA的水平,应用蛋白印记杂交方法观察AQP-1蛋白改变情况.结果 应用PDS治疗后AQP-1在mRNA和蛋白水平均有所增加,减轻了肺水肿、肺损伤.结论 在SAP时应用PDS可以抑制TNF-α、IL-6表达,减轻血液浓缩,改善微循环,增加肺组织水通道蛋白1的表达,从而减轻肺水肿、肺损伤.     

沙利度胺对大鼠急性胰腺炎肺损伤核因子-κB信号通路的作用

目的观察沙利度胺抗大鼠急性胰腺炎相关性肺损伤的疗效和对核因子-κB(NF-κB)信号通路的影响。方法 5%牛磺胆酸钠胰胆管注射制备急性胰腺炎模型,治疗组于造模前用沙利度胺100 mg/kg灌胃8 d。观察胰腺和肺组织病理学改变,检测肺组织的湿/干比率、血淀粉酶及血氧分压水平,Western blotting检测肺组织NF-κBp65、NF-κB抑制因子α(IκBα)、肿瘤坏死因子-α(TNF-α)蛋白表达,RT-PCR检测肺组织NF-κBp65、TNF-αmRNA表达。结果沙利度胺治疗组大鼠胰腺组织及肺组织病理学评分显著低于模型组(P0.01);其肺组织的湿/干比率、血淀粉酶、NF-κBp65和TNF-αmRNA及蛋白表达,均显著低于模型组(P0.01);而血氧分压水平和IκBα蛋白表达高于模型组(P0.01)。结论沙利度胺可以有效地抑制急性胰腺炎相关性肺损伤的进展,通过抑制NF-κB信号通路对TNF-α表达的诱导可能是其发挥作用的重要机制之一。     

硫氧还蛋白-1在急性坏死性胰腺炎大鼠肺组织中的表达及褪黑素干预的影响

目的:探讨内源性硫氧还蛋白-1(Trx-1)在急性坏死性胰腺炎(ANP)大鼠模型肺组织中的表达:观察褪黑素对ANP胰和肺脏的保护作用和对肺组织Trx-1表达的影响.方法:将72只SD大鼠随机分成对照组(C组,n=24)、急性胰腺炎组(A组,n=24)、褪黑素前干预组(M组,n=24).A组用6%的左旋精氨酸(L-Arginine,L-Arg)腹腔内注射,每次25 mL/kg体质量,共3次,注射间隔1 h,诱导ANP模型,在首次注射L-Arg前30 min腹腔注射生理盐水20mL/kg体质量1次;C组同法注射相当于A组各次注射用量的等容积生理盐水:M组在诱导胰腺炎前30 min腹腔内注射0.25%褪黑素(20mL/kg体质量)干预.在注射完L-Arg后的6、12、24 h三个时点分批处死大鼠.应用免疫组织化学技术检测各组ANP肺组织Trx-1的表达.并观察各组对应各时点胰腺、肺组织病理学和肺免疫组织化学的改变;抽取动脉血测定Trx-1和淀粉酶.结果:A组大鼠胰腺和肺组织病理损伤在6、12、24 h时点比C组明显加重(均P＜0.01);M组胰腺和肺组织病理损伤在6、12、24 h时点较A组明显减轻(P＜0.01或0.05).A组、M组肺组织表达Trx.1量在6、12、24 h时点较C组显著升高(均P<0.01).在24 h,A组血清淀粉酶较C组显著升高(4 598 U/L±2 274 U/L vs2 033U/L±863 U/L,P＜0.01);M组较A组低(3 990U/L±1 146 U/L vs 4 598 U/L±2 274 U/L,P＜0.05).A组大鼠血清Trx-1含量在6、12 h时点显著降低,24 h时点显著升高,呈前低后高趋势;与A组比较,M组血清Trx-1在6、12 h时点显著升高,24 h时点显著降低,量的峰值前移.结论:Trx-1在ANP肺损伤组织中的过度表达与急性胰腺炎相关性肺损伤关系密切.褪黑素影响Trx-1表达,并可能在一定程度上减轻ANP的胰、肺组织损伤.     

Severe acute pancreatitis in acute hepatitis E.

We report an 18-year-old boy with severe acute pancreatitis developing during acute hepatitis E and complicated by sepsis and acute renal failure. The patient recovered on supportive management.     

重症急性胰腺炎患者发生急性期急性肺损伤的危险因素分析

目的探讨重症急性胰腺炎(SAP)患者发生急性期急性肺损伤(ALI)的相关危险因素。方法选取114例SAP患者为研究对象,根据其发生急性期ALI的情况分成损伤组(n=36)和非损伤组(n=78)。回顾性分析两组患者的临床资料,对单因素分析后存在显著性差异的指标行非条件Logistic回归分析。结果(1)两组患者性别、病因、平均住院天数、血糖浓度及慢性疾病史等一般资料比较差异无统计学意义(P0.05);损伤组年龄、病程、Ranson评分均显著高于非损伤组(P0.01);且损伤组器官受累≥2个、腹腔感染率、机械通气治疗率、合并全身炎症反应综合征(SIRS)率均显著高于非损伤组(P0.01);APACHEⅡ评分8分率、吸烟史率则显著低于非损伤组(P0.01)。(2)非条件Logistic回归方程显示年龄、病程、合并SIRS、器官受累情况、机械通气治疗、腹腔感染、Ranson评分等均为SAP患者发生急性期ALI的独立危险因素(P0.05);吸烟及APACHEⅡ8分则为SAP患者发生急性期ALI的保护因素(P0.05)。结论年龄、病程、器官受累情况、机械通气治疗、腹腔感染、Ranson评分、合并SIRS等均为SAP患者发生急性期ALI的独立危险因素,需引起临床重视。     

Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults

One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c- ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.     

ERCP in acute pancreatitis

BACKGROUND: The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute pancreatitis has evolved over years since its introduction in 1968. Its importance in diagnosing the etiology of pancreatitis has steadily declined with the advent of less invasive diagnostic tools. The therapeutic implications of ERCP in acute pancreatitis are many fold and are directed towards management of known etiological factors or its related complications. This article highlights the current status of ERCP in acute pancreatitis. DATA SOURCES: An English literature search using PubMed database was conducted on ERCP in acute pancreatitis, the etiologies and complications of pancreatitis amenable to endotherapy and other related subjects, which were reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management of biliary pancreatitis in specific situations, pancreatitis due to microlithiasis, specific types of sphincter of Oddi dysfunction, pancreas divisum, ascariasis and malignancy. In recurrent acute pancreatitis and smoldering pancreatitis it has a definite therapeutic utility. Complications of acute pancreatitis including pancreatic-duct disruptions or leaks, benign pancreatic-fluid collections and pancreatic necrosis can be beneficially dealt with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in detecting pancreatic malignancy. CONCLUSIONS: The role of ERCP in acute pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role in the management continues to evolve and advanced invasive procedures should be undertaken only in centers dedicated to pancreatic care.     

Troxacitabine in acute leukemia

Troxacitabine (Troxatyl; BCH-4556; (–)-2′-deoxy-3′-oxacytadine) is the first synthetic L-nucleoside enantiomer to demonstrate broad spectrum cytotoxic activity. It was obtained by exchanging the sulphur endocyclic atom with oxygen in the structure of lamivudine, following the discovery that this agent had cytotoxic, as well as anti-viral activity. The unique "unnatural" stereochemistry of troxacitabine has produced impressive cytotoxic potency against a wide range of malignancies in the laboratory which led to its selection for clinical development. The initial trials with troxacitabine have established its efficacy in both solid and haematological malignancies, including those resistant to ara-C (cytarabine). This review will consider troxacitabine in terms of its pharmacology, mode of action, pharmacokinetics, tolerability and clinical efficacy.