活血化瘀汤对髌骨骨折患者膝关节功能及炎症因子的影响

目的:探讨髌骨骨折患者应用活血化瘀汤对患者膝关节功能、炎症因子的影响。方法:选择2015年3月到2017年3月西南医科大学附属中医医院接诊的髌骨骨折患者100例作为研究对象,以随机数表法分为观察组(n=53)和对照组(n=47),两组患者均采用切开复位克氏针张力带内固定,观察组加用活血化瘀汤。比较两组治疗后膝关节优良率、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、膝关节功能Lysholm评分、视觉模拟评分法(VAS)评分及不良反应发生情况。结果:治疗后,观察组患者优良率为92.45%,显著高于对照组的72.34%(P0.05);治疗前,两组患者TNF-α、IL-6及IL-10水平无显著差异(P0.05);治疗后,两组TNF-α、IL-6及IL-10水平较治疗前均显著改善(P0.05),且观察组TNF-α、IL-6均明显低于对照组,IL-10水平显著高于对照组(P0.05);治疗前,两组患者Lysholm评分、VAS评分无显著差异(P0.05);治疗后,两组Lysholm评分、VAS评分较治疗前均显著改善(P0.05),且观察组Lysholm评分均明显高于对照组,VAS评分显著低于对照组(P0.05);观察组患者不良反应总发生率为1.89%,显著低于对照组的14.89%,差异具有统计学意义(P0.05)。结论:在髌骨骨折患者中使用活血化瘀汤效果显著,可有效改善患者膝关节功能、炎症因子水平,值得推广与运用。     

保留灌肠清胰汤联合ERCP治疗急性胆源性胰腺炎的疗效及机制探讨

目的:探讨保留灌肠清胰汤联合内镜逆行胰胆管造影术(endoscopic retrograde pancreatic cholangiography,ERCP)治疗急性胆源性胰腺炎的临床疗效及作用机制。方法:选择2015年1月～2017年12月我院收治的97例胆源性胰腺炎患者为研究对象,根据治疗方法不同,将其分为对照组(ERCP组,46例)及观察组(保留灌肠清胰汤联合ERCP组,53例)。观察和比较两组的中医临床疗效,治疗前后7天的肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、C反应蛋白(c-reactive protein,CRP)、白细胞介素-6(Interleukins-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)、白细胞介素-10(Interleukin-10,IL-10)水平及治疗前、治疗后12 h、24 h、3 d的血清淀粉酶水平的变化,腹痛缓解时间、平均住院时间、平均住院费用。结果:治疗后,观察组的痊愈、显效比例明显高于对照组(P0.05)。两组治疗后的血清TNF-α、CRP、IL-6、IL-8、IL-10水平均显著低于治疗前,且观察组的血清TNF-α、CRP、IL-6、IL-8水平均明显低于对照组(P均0.05);两组的平均住院费用对比差异无统计学意义(P0.05);观察组的腹痛缓解时间、平均住院时间明显低于对照组(P0.05)。与治疗前相比,两组治疗后12 h、24 h、3 d时的血清淀粉酶水平均显著降低,且观察组治疗后12 h、24 h时的血清淀粉酶水平均明显低于对照组(P均0.05)。结论:保留灌肠清胰汤联合ERCP治疗可显著提高急性胆源性胰腺炎的治疗痊愈率及有效率,其作用机制可能与降低患者血清TNF-α、CRP、IL-6、IL-8及淀粉酶水平有关。     

尼美舒利联合甲硝唑对牙周炎患者血清IL-10、TNF-α和MMP-8水平的影响

目的:研究尼美舒利联合甲硝唑对牙周炎患者血清白细胞介素-10(IL-10)、肿瘤坏死因子(TNF-α)、基质金属蛋白酶-8(MMP-8)水平的影响。方法:收集2014年3月至2015年3月我院收治的90例牙周炎患者,按照抽签法分为实验组和对照组,每组各45例。两组均采用牙结石以及牙菌斑除去、根面平整、冲洗牙周袋等常规治疗。对照组在此基础上采用甲硝唑治疗,0.9%生理盐水进行冲洗。实验组在对照组基础上采用尼美舒利治疗,每次2片,每天2次。观察和比较两组的治疗疗效,牙周情况,治疗前后血清IL-10、TNF-α、MMP-8水平的变化及不良反应的发生情况。结果:治疗后,实验组总有效率显著高于对照组(P0.05);GI、PD、PLI、AL显著低于对照组(P0.05);血清IL-10水平显著高于对照组(P0.05),血清TNF-α、MMP-8水平显著低于对照组(P0.05);两组不良反应总发生率比较差异无统计学意义(P0.05)。结论:尼美舒利联合甲硝唑治疗牙周炎可显著提高其临床疗效,消除或缓解临床症状,可能与其提高血清IL-10水平,降低TNF-α、MMP-8水平,抑制炎症反应,保持牙内环境稳定有关。     

美沙拉嗪联合双歧三联活菌对溃疡性结肠炎患者TNF-α、IL-8及IL-10水平的影响

目的:探讨美沙拉嗪联合双歧三联活菌治疗溃疡性结肠炎(UC)的临床疗效及对患者TNF-α、IL-8及IL-10水平的影响。方法:选择2013年1月~2014年1月我院收治的UC患者60例,随机分为研究组与对照组,每组30例。对照组患者应用美沙拉嗪治疗,研究组在此基础上联合双歧三联活菌治疗。观察两组临床疗效、血清TNF-α、IL-8及IL-10水平变化及药物不良反应。结果:研究组治疗的总有效率为86.67%,显著高于对照组的63.33%(P0.05);治疗后,两组TNF-α、IL-8水平显著降低,IL-10水平显著升高(均P0.01),研究组TNF-α、IL-8显著低于对照组,IL-10水平显著高于对照组(均P0.05);研究组不良反应发生率为6.67%,明显低于对照组的33.33%(P0.05)。结论:美沙拉嗪联合双歧三联活菌对UC患者黏膜的保护作用显著,且有效抑制UC相关的炎性反应,安全可靠,适于临床推广与应用。     

沙丁胺醇联合福多司坦治疗慢性阻塞性肺疾病稳定期的疗效及对患者血清IL-6、TNF-α、hs-CRP水平的影响

目的:探讨沙丁胺醇联合福多司坦治疗慢性阻塞性肺疾病稳定期的临床疗效及对患者血清白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、超敏c反应蛋白(hs-CRP)水平的影响。方法:选择2016年1月到2017年1月我院接诊的稳定期慢性阻塞性肺病患者100例作为研究对象,按照随机数表法分为观察组(n=51)和对照组(n=49)。对照组使用沙丁胺醇治疗,观察组采用沙丁胺醇联合福多司坦治疗。比较两组治疗后的疗效、治疗前后血清IL-6、TNF-α、hs-CRP、肺功能的变化及不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率(94.12%)显著高于对照组(75.51%,P0.05)。两组患者治疗后血清IL-6、TNF-α、hs-CRP水平均治疗前均明显下降,且观察组患者血清IL-6、TNF-α、hs-CRP水平均明显低于对照组(P0.05);两组治疗后各第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、最大呼气流量(PEF)较治疗前均显著升高(P0.05),且观察组FEV1、FVC、PEF均明显高于对照组(P0.05);两组患者不良反应总发生率分别19.61%、38.78%,观察组显著低于对照组(P0.05)。结论:沙丁胺醇联合福多司坦治疗慢性阻塞性肺疾病稳定期的临床疗效和安全性均显著优于单用沙丁胺醇治疗,可能与其有效改善患者血清IL-6、TNF-α、hs-CRP水平有关。     

美常安联合柳氮磺吡啶治疗溃疡性结肠炎的疗效及对血清TNF-α、IL-6、IL-8水平的影响

目的:探索美常安联合柳氮磺吡啶治疗溃疡性结肠炎(UC)的疗效,及对血清TNF-α、IL-6、IL-8水平的影响。方法:选择自2012年9月至2014年12月我院收治的100例UC患者,按照随机数表法分成对照组和观察组,每组50例。对照组患者口服给予柳氮磺吡啶,观察组患者口服给予美常安联合柳氮磺吡啶治疗。统计分析两组患者的临床有效率、症状改善、不良反应发生情况及治疗前后患者血清中TNF-α、IL-6、IL-8水平的变化。结果:观察组中总有效率为92.00%显著高于对照组中总有效率为48.00%(P0.05);两组患者治疗后的主要临床症状较治疗前均有明显改善(P0.05),且观察组患者治疗后主要症状缓解率明显高于对照组(P0.05);两组患者治疗后血清中TNF-α、IL-6、IL-8水平均显著低于治疗前,且观察组明显低于对照组(P0.05);两组患者不良反应发生率之间的差异无统计学意义(P0.05)。结论:美常安联合柳氮磺吡啶治疗UC具有良好的临床疗效,能显著改善患者的临床症状和患者血清中炎症因子的水平,值得在临床上推广使用。     

氨溴索注射液治疗COPD合并肺结核患者的疗效及对血清IL-6、TNF-α水平的影响

目的:观察氨溴索注射液治疗慢性阻塞性肺疾病(COPD)合并肺结核(PTB)患者的临床疗效及对患者血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平的影响。方法:选取2015年1月～2018年1月我院诊治的COPD合并PTB患者181例,按照入院先后顺序分为对照组和观察组。对照组90例,给予常规对症药物治疗。观察组91例,在对症治疗的基础上加用氨溴索注射液。两组均持续治疗8周。比较两组临床有效率、病灶吸收和空洞闭合有效率、临床症状积分、肺功能及治疗前后血清IL-6和TNF-α水平的变化。结果:治疗后,观察组和对照组的总有效率分别为95.60%、74.44%,观察组显著高于对照组,两组相比具有统计学差异(P0.05);观察组治疗后病灶吸收有效率和症状积分均明显优于对照组(P0.05),空洞闭合有效率与对照组相比差异无统计学意义(P0.05);观察组治疗后用力呼气量(FVC)、一秒用力呼气容积(FEV1)和FEV1/FVC值显著高于对照组(P0.05),血清IL-6和TNF-α水平均显著低于对照组(P0.05)。结论:氨溴索注射液可显著提高COPD合并PTB患者的临床疗效,改善临床症状、病灶吸收和空洞闭合有效率和肺功能,可能与其有效降低血清IL-6和TNF-α水平有关。     

玻璃酸钠联合臭氧关节腔内注射对创伤性踝关节炎患者血清hs-CRP、IL-1β、IL-6和TNF-α水平的影响

目的:探讨玻璃酸钠联合臭氧关节腔内注射对创伤性踝关节炎患者血清超敏C反应蛋白(hs-CRP)、白介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α水平的影响。方法:选择2013年1月至2016年8月我院接诊的92例创伤性踝关节炎患者作为本次研究对象,通过随机数表法分为观察组(n=46)和对照组(n=46)。对照组在关节腔给注射玻璃酸钠治疗,观察组联合臭氧治疗,均1次/周,连续治疗5次。比较两组治疗前后视觉模拟评分法(VAS)、Mc Guire踝关节评分以及血清hs-CRP、IL-1β、IL-6和TNF-α的变化及治疗后临床疗效优良率。结果:治疗前,两组VAS评分、Mc Guire踝关节评分、血清hs-CRP、IL-1β、IL-6和TNF-α水平比较差异均无统计学意义(P0.05)。治疗后,两组VAS评分、Mc Guire踝关节评分均较治疗前显著改善(P0.05),且观察组VAS评分明显低于对照组,Mc Guire踝关节评分明显高于对照组(P0.05);两组血清hs-CRP、IL-1β、IL-6和TNF-α水平较治疗前均显著降低(P0.05),且观察组血清hs-CRP、IL-1β、IL-6和TNF-α比较均明显低于对照组(P0.05);观察组临床疗效优良率明显高于对照组(P0.05)。结论:关节腔内注射玻璃酸钠联合臭氧治疗创伤性踝关节炎患者的临床效果优于单用关节腔注射玻璃酸钠,可有效缓解疼痛,改善关节功能,可能与其有效降低血清hs-CRP、IL-1β、IL-6和TNF-α水平有关。     

板蓝根联合阿奇霉素对小儿支原体肺炎血清炎症因子影响

目的:探究板蓝根联合阿奇霉素对小儿支原体肺炎患者血清中TNF-α、IL-6、IL-8和IL-10浓度的影响。方法:选择2014年1月-2014年12月在我院接受治疗的患儿80例,均确诊为支原体肺炎,按随机数字表分为实验组和对照组。对照组给予阿奇霉素粉针剂与阿奇霉素治疗。实验组在对照组基础上给予板蓝根提取液治疗。观察并比较两组治疗前后外周血TNF-α,IL-6,IL-8及IL-10水平的变化情况及疗效与不良反应发生率。结果:实验组的临床治疗的总有效率较高(P0.05);治疗后两组促炎因子TNF-α、IL-6、IL-8水平均明显下降(P0.05),与对照组相比,实验组TNF-α、IL-6、IL-8水平较低(P0.05);治疗后两组患儿血清抗炎因子IL-10水平均下降(P0.05),与对照组相比,实验组IL-10较低(P0.05);与对照组相比,实验组不良反应发生率较低(P0.05)。结论:板蓝根联合阿奇霉素能够明显降低小儿支原体肺炎患者血清中TNF-α、IL-6、IL-8和IL-10的浓度,提高治疗效果,对临床有指导意义。     

阿托伐他汀联合厄贝沙坦对老年早期糖尿病肾病患者肾功能及微炎症状态的影响

目的:探讨阿托伐他汀联合厄贝沙坦对老年早期糖尿病肾病(DN)患者肾功能及微炎症状态的影响。方法:选取2016年4月到2017年2月在我院肾内科接受治疗的老年早期DN患者84例,根据随机数字表法将患者分为对照组和观察组,各42例。对照组给予厄贝沙坦进行治疗,观察组给予阿托伐他汀联合厄贝沙坦进行治疗。比较两组患者的尿微量白蛋白排泄率(UAER)及两组患者血肌酐(Scr)、血尿素氮(BUN)、β2微球蛋白(β2-MG)、白细胞介素-1(IL-1)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平,并比较两组患者治疗过程中出现的不良反应。结果:治疗后两组患者的UAER、Scr、BUN、β2-MG水平均降低,且观察组的UAER、Scr、BUN、β2-MG均低于对照组(P0.05)。治疗后两组患者血清中IL-1、TNF-α水平均降低,IL-10水平升高(P0.05);治疗后观察组血清中IL-1、TNF-α水平低于对照组,IL-10水平高于对照组(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:阿托伐他汀联合厄贝沙坦对老年早期DN患者有较好的治疗效果,可显著改善患者的肾功能,减轻微炎症状态,且安全性较好,值得临床推广应用。     

Synthetic Approaches to a Mononucleotide Prodrug of Cytarabine

Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S-pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are reported. Using a common phosphoramidite approach, two different kinds of nucleoside protecting groups have been investigated. During this study, we observed an intermolecular migration of the Boc protecting group in the course of the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.     

Sequential Treatment with Cytarabine and Decitabine Has an Increased Anti-Leukemia Effect Compared to Cytarabine Alone in Xenograft Models of Childhood Acute Myeloid Leukemia

The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered.     

全细胞催化合成阿糖胞苷工艺的研究

以阿糖尿苷和胞嘧啶为原料,采用枯草芽胞杆菌Bacillus subtilis A302作为全细胞催化剂进行阿糖胞苷的生物合成,通过单因素与正交试验的考察,得到了全细胞催化合成阿糖胞苷的最佳反应条件:反应初始pH为7.0,反应温度为36℃,催化剂添加量为250 mg,摇床转速为190 rpm,该条件得到的阿糖胞苷收率达到65.3％.该方法操作简单,反应体系杂质较少,是合成阿糖胞苷的一种有效可行的方法.     

Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia

Background

To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.

Methods

A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.

Results

Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.

Conclusion

Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.     

聚乙二醇-20000对阿糖胞苷脂质体载药性能的影响

目的：探讨聚乙二醇-20000对阿糖胞苷脂质体载药性能的影响。方法：用蛋黄卵磷脂为包封材料,采用逆相蒸发法制备阿糖胞苷脂质体,用不同质量浓度的聚乙二醇包覆进行表面修饰,与未包覆的脂质体进行对照,通过测定其包封率、平均粒径、粒度分布及药物的渗漏速率,对聚乙二醇．20000修饰的阿糖胞苷脂质体的载药性能进行评价。结果：聚乙二醇-20000修饰的阿糖胞苷脂质体具有较高的包封率、较大的平均粒径和较低的渗漏速率。p（PEG）=2．0g/L时,包封率最高为（22．34±2．47）％,平均粒径最大为5．99μm。p（PEG）=4．0g/L时,渗漏速率最慢。结论：聚乙二醇-20000的修饰提高了阿糖胞苷脂质体的载药性能。     

Biologic Activity of a Nucleotide Conjugate Between Mitomycin C and Cytarabine Monophosphate

Abstract

A dual prodrug conjugate between the antimetabolite cytarabine monophosphate and the alkylating agent 2,7-diaminomitosene (derived from mitomycin C), cytaramycin, was synthesized and tested for antileukemic activity in sensitive and resistant tumors. The compound was active against parental L-1210, CCRF-CEM, HL-60 and K-562 leukemia cells but did not overcome resistance in sublines developed for (1) multidrug resistance (L-1210/MDR and K-562-R) or (2) for cytarabine resistance (CCRF-CEM/ARA-C and HL-60/ARA-C). Alkaline DNA elution tests demonstrate a predominance of strand breaking activity due to the cytarabine moiety, and a lesser degree of DNA crosslinking, due to the mitosene moiety. The conjugate was active in mice bearing P-388 leukemia (80% increased lifespan), but was not more effective than mitomycin C alone in mice bearing a cytarabine-resistant L-1210 cell line (38% to 31% increased lifespan). These findings suggest that mitomycin nucleotide conjugates do not overcome resistance to the parent antimetabolites.     

靶向抑制miRNA-21提高白血病K562细胞对阿糖胞苷的敏感性

为研究以miRNA-21为靶标的反义核酸(AMO-miR-21)提高白血病K562细胞对阿糖胞苷(Ara-C)的敏感性及可能的作用机制,在LipofectamineTM2000介导下,将化学合成的AMO-miR-21转染K562细胞,四甲基偶氮唑蓝(MTT)法检测单独使用AMO-miR-21、Ara-C以及两者联合使用对细胞增殖抑制作用,并计算抑制率和IC50;流式细胞仪检测细胞凋亡;实时定量PCR(Real-time PCR)检测miRNA-21及其候选靶基因Pdcd4 mRNA的表达水平;免疫印迹(Western blot)检测Pdcd4蛋白的表达水平.结果显示Ara-C与AMO-miR-21联合使用后,IC50从1.95μmol/L降低到0.84μmol/L,敏感性提高到单用Ara-C的2.3倍.AMO-miR-21联合Ara-C组细胞凋亡明显增加(P<0.05).AMO-miR-21显著抑制K562细胞中miRNA-21的表达水平(P<0.05),同时Pdcd4的表达明显增加(P<0.05).提示AMO-miR-21可以提高K562细胞对Ara-C的敏感性,其作用机制与靶向抑制miRNA-21,进而诱...     

Immunocytochemical Detection of Deoxycytidine Kinase in Pediatric Malignancies in Relation to In Vitro Cytarabine Sensitivity

Deoxycytidine kinase (dCK) is essential for the phosphorylation of cytarabine (ara‐C), a deoxycytidine analog active against acute leukemias. Resistance to ara‐C has been linked to dCK deficiency. In this study we determined the expression of the dCK protein in pediatric malignancies, using immunocytochemistry and related the expression levels to in vitro ara‐C sensitivity (measured with the MTT‐assay). dCK expression was high in the AML and retinoblastoma samples, in the ALL samples dCK expression ranged from low to very high. The brain tumor samples expressed low levels of dCK. AML was significantly more sensitive in vitro to ara‐C compared to ALL (p = 0.03). Retinoblastoma and brain tumor cells were extremely resistant in vitro, we were unable to detect more than 50% ara‐C induced cell kill in the majority of samples. Samples were combined in groups according to dCK expression. Samples with low dCK expression were significantly more resistant to ara‐C compared to samples with high dCK expression. In conclusion, dCK expression varies between individual samples and between different types of malignancies and may play a role in resistance to ara‐C in particular tumor types.     

High-Dose Cytarabine in Acute Myeloid Leukemia Treatment: A Systematic Review and Meta-Analysis

The optimal dose, scheme, and clinical setting for Ara-C in acute myeloid leukemia (AML) treatment remain uncertain. In this study, we performed a meta-analysis to systematically assess the impact of high-dose cytarabine (HDAC) on AML therapy during the induction and consolidation stages. Twenty-two trials with a total of 5,945 de novo AML patients were included in the meta-analysis. Only patients less than 60 year-old were included in the study. Using HDAC in induction therapy was beneficial for RFS (HR = 0.57; 95% CI, 0.35–0.93; P = 0.02) but not so for CR rate (HR = 1.01; 95% CI, 0.93–1.09; P = 0.88) and OS (HR = 0.83; 95% CI, 0.66–1.03; P = 0.1). In consolidation therapy, HDAC showed significant RFS benefits (HR = 0.67; 95% CI, 0.49–0.9; P = 0.008) especially for the favorable-risk group (HR = 0.38; 95% CI, 0.21–0.69; P = 0.001) compared with SDAC (standard dose cytarabine), although no OS advantage was observed (HR = 0.84; 95% CI, 0.55–1.27; P = 0.41). HDAC treatment seemed less effective than auto-BMT/allo-BMT treatment (HR = 1.66, 95% CI, 1.3–2.14; P<0.0001) with similar OS. HDAC treatment led to lower relapse rate in induction and consolidation therapy than SDAC treatment, especially for the favorable-risk group. Auto-BMT/allo-BMT was more beneficial in prolonging RFS than HDAC.     

Modulation of Cytarabine Induced Cytotoxicity Using Novel Deoxynucleoside Analogs in the HL60 Cell Line

In order to enhance the cytotoxicity of ara‐C in the HL60 cell line the following deoxynucleoside analogs were used: cladribine, fludarabine and gemcitabine. HL60 cells were co‐incubated with ara‐C and each of the modulators at the ratios of their respective IC50s. Cytotoxicity was determined with the MTT‐assay and drug interactions were evaluated with the combination index (CI) method (Calcusyn; Chou & Talalay). CI < 1, CI ± 1 and > 1 indicate synergism, additive effect and antagonism, respectively. We observed moderate synergism between ara‐C/cladribine and ara‐C/gemcitabine, with CIs of 0.76 ± 0.14 and 0.82 ± 0.04, respectively. The interaction between ara‐C/fludarabine resulted in moderate antagonism (CI = 1.29 ± 0.11). In conclusion, in this in vitro study we showed that the cytotoxicity of ara‐C can be succesfully modulated in the HL60 cell line by cladribine and gemcitabine.