Interaction between cisplatin,5-fluorouracil and vincristine on human hepatoma cell line (7721)

AIM To evaluate the killing effects of CDDP, 5-Fu and VCR on human hepaoma cell line (7721).METHODS The median-effect principle was used.RESULTS Killing effects of the individual drug were enhanced as the median concentration increased. Antagonism was produced when two drugs were used at a higher concentration (CI＞1), and synergism was achiened when CI＜1. Finally, the effect was influenced by both the ratios of drug concentration and the sequence of administration.CONCLUSION The drug administration order and drug concentrations are significant factors that need to be considered in clinical practice.INTRODUCTIONThe combined chemotherapy for malignant carcinoma is desired to produce efficacious synergism between each drug, alleviate side effects of drugs and delay drug resistance. Clinically, the interaction (namely synergism, summation and antagonism) of different anticancer drugs in combination is usually evaluated by Chou-Talalay′s combination index (i.e., median-effect principle)[1-9]. In this paper the combination effect between Cisplatin (Cis), 5-Fluorouracil (5-Flu) and Vincristine (VCR) on human hepatoma cell line 7721, was analyzed in vitro.

Preparation of anti-resistant stealthy liposomes by incorporating vincristine with quinacrine and the pharmacokinetics in Sprague-Dawley rats

Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.

Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy

We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.

Mechanism of all-transretinoic acid increasing retinoblastoma sensitivity to vincristine

Objective: To explore the mechanism of all-transretinoic acid (ATRA) increasing retinoblastoma (RB) sensitivity to vincristine, and the inhibiting effect of vincristine combined with ATRA treatment on the SO-RB50 cell proliferation. Methods: SO-RB50 cells were cultivated by routine culture method. Different concentrations of vincristine or ATRA were added into culture solution. After 48 h, cell counting kit-8 was used to detect the median inhibitory concentration (IC50) of vincristine combined with ATRT treatment to SO-RB50 cells. SO-RB50 cells were divided into drug combination group, vincristine group, ATRA group and control group. Different drugs were added into the culture solution respectively for cell culture based on the IC50 value. Cell counting kit-8 was used to detect the cell proliferation every 24-h cultivation. After continuous determination for 6 d, data was processed to draw the cell growth curve. After drug use for 72 h, flow cytometry was used to detect the proportion of different cell cycles of SO-RB50 cells in each group. After drug use for 48 h, annexin V/propidium iodide method was used to detect the SO-RB50 cell apoptosis in each group. Results: The IC50 value of vincristine treatment on the SO-RB50 cells was 0.11 mu mol/L, and ATRT was 12.84 mu mol/L. The cell growth curve in control group rose gradually along with the extended culture time, but after vincristine and ATRA treatment, the cell growth curve was smooth and steady. The cell increment was the least in drug combination group and its cell growth curve was the smoothest. There was significant difference in A(450) 48 h and 72 h after treatment (F-grouping=77.316, P<0.001: F-time=86.985, P<0.001). Compared with control group. A(450) value in drug combination group, vincristine group, ATRA group was significantly lower (P<0.001). Compared with control group, the G(2)/M phase cell proportion in vincristine group was significantly increased, while the G(0)/G(1) phase cell proportion was significantly decreased; the G(0)/G(1) phase cell proportion in ATRA group was significantly increased, while the S phase cell proportion was significantly decreased (F-G0/G1=85.878, F-s=56.455, F-G2/M=85.878, P<0.001). After 48 h, there was significant difference in SO-RB50 cell apoptosis rate among groups (F=11.312, P<0.05). The apoptosis rate in drug combination group was significantly higher than that of other groups (P<0.001). Conclusions: ATRA can increase the sensitivity of SO-RB50 cells to vincristine. Vincristine combined with ATRA treatment can significantly increase the inhibiting effect on SO-RB50 cells, which may be related with promoting cell apoptosis and involving in cell cycle control.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

Preparation and quality evaluation of vincristine sulfate-loaded PEG-PLGA nanoparticles

Objective To prepare the PEG-PLGA nanoparticles loaded with vincristine sulfate(VCR-loaded PEG-PLGA-NPs) and evaluate their quality.Methods VCR-loaded PEG-PLGA-NPs were prepared by the double emulsion solvent evaporation method.The main experimental factors,which influenced the physical and chemical properties of the nanoparticles,were investigated and optimized.Results Under optimal conditions,the VCR-loaded PEG-PLGA-NPs had an average diameter of 135.9 nm with narrow size distribution.The encapsulation efficiency was 68.2%,while the drug loading capacity was 8.34%.In vitro,VCR was released from the PEG-PLGA-NPs sustainedly for more than 13 days with the total amount of 81%.Moreover,the VCR-loaded PEG-PLGA-NPs were relatively stable,which was confirmed by the stability testing.Conclusion The VCR-loaded PEG-PLGA-NPs are a promising nano drug with controlled release,which can be applied widely.

The interaction between cytarabine and vincristine on HL-60 cell line in vitro

Objective： To analyze the effect of cytarabine combined with vincristine on HL-60 cell line in vitro. Methods： The median-effect equation and MTr assay were used on HL-60. Results： The cytotoxic activity of cytarabine（Ara-C） and vincristine （VCR） used alone or in combination enhanced as drug concentration increased. The order of administration did not influence the cytotoxic activity of the combined antitumor drugs. The ratio of drug concentration was a factor to influence the killing effect. The interaction of the agents was synergistic at lower concentration, and antagonistic at higher concentration. Conclusion： The combined drugs interaction（CI 〈 1 ） was synergistic at lower concentration and antagonistic at higher concentration. The ratio of drug concentration is a significant factor that can influence the killing effect.

Randomized Trial Comparing Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF) Regimen with Rotational CMFEV Regimen (E=Epirubicin, V=Vincristine) as Adjuvant Chemotherapy in Moderate Risk Operable Breast Carcinoma

Objectives: The CMFEV (cyclophosphamide, methotrexate, 5-fluorouracil, epirubicin, vincristine) regimen is an innovative schedule, designed by our Group, aimed at administering five partially or totally no cross-resistant cytotoxic agents in breast carcinoma. It was randomly compared to CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as primary treatment in operable disease and demonstrated a short-term significant increase in clinical complete response rate and a long-term significant locoregional relapse-free survival in premenopausal patients. So, it seemed worth comparing this regimen with CMF as adjuvant chemotherapy in moderate risk operable breast carcinoma. Methods: Four hundred and eighty-nine patients with stage I or II moderate risk breast carcinoma were randomized to receive CMF or CMFEV regimen for 6 cycles after surgery. Main end points were overall survival (OS), invasive disease-free survival (IDFS) and recurrence-free interval (RFI), as estimated by Kaplan-Meier analyses and log-rank tests. Results: At a median observation time of 7.3 years (range 5.4 months-10.3 years), no significant differences in OS and IDFS were observed between the two arms. Deaths from breast carcinoma were more frequent with CMF (58.5%) than with CMFEV regimen (41.7%) as well as recurrences from breast carcinoma (58.8% with CMF and 41.2% with CMFEV). These differences were not statistically significant. Conclusion: CMFEV appears more effective than CMF in preventing recurrences from primary disease in patients with moderate risk stage I-II breast carcinoma. The lack of statistical significance of the observed differences was probably due to the limited number of patients enrolled which rendered the study underpowdered.

Unilateral Ptosis in a Child with Wilm’s Tumor Induced by Vincristine

Vincristine is a chemotherapy drug belonging to the group of Vinca alkaloids which also includes vinblastine and vindesine. It is used in hematological malignancies and solid tumors. The Vinca alkaloids are neurotoxic, usually causing peripheral neuropathy, and rarely cranial neuropathies. We report a case of a 33-month-old male child diagnosed with Wilms’ tumor, who had an isolated unilateral right ptosis following vincristine, with a good improvement after stopping it.

Side Effects of Vincristine and L-Asparaginase in Patients with Acute Lymphoblastic Leukemia in a Mexican Pediatric Hospital

Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.

试论深孔爆破成井中VCR法的应用

VCR模式为球形药包垂向漏斗后嵌类矿场技术,地底矿石洞也普及推广使用在天井挖掘作业中。笔者以某露天兼地底采掘金石七十米标高地表废弃石料场景为项目环境,透过实验参数明确爆破工程中的药包最理想埋进情况。生产实际表明,透过使用适度的凿孔设施,适度的先进工艺,VCR模式能够挖掘超高矿井,而且能够保证矿井工程进度。

VCR法采空区爆破成井技术的研究与应用

呼伦贝尔山金铅锌矿采用充填法治理历史采空区,由于采空区充填井采用普通法掘进效率低、作业条件及安全性差,采用采空区充填井安全高效施工技术成为关键。根据利文斯顿爆破漏斗理论,通过前期进行的大量试验爆破,确定最佳爆破参数,结合现场条件研究提出VCR法爆破快速成井技术方案。实践结果表明,VCR法在爆破采空区充填井上取得了良好的应用效果,成功开掘了直径2.0 m、深度17.4 m的充填井。重点对爆破参数、装药结构、堵孔方式以及施工过程中存在的问题进行分析总结,为同类矿山提供一定的参考和借鉴。

VCR采矿法深孔爆破大块率控制经验浅谈

在实际矿山爆破工程中,采用VCR采矿法进行爆破时,其爆破规模较大,易产生大块岩石,增加了二次爆破成本,增加了出矿难度,同时降低了出矿效率。根据实际工程中的爆破经验,提出了大块率的计算方法,分析了爆破过程中大块产生的多种原因,并结合草楼铁矿的具体条件,针对炮孔孔网参数进行了相应的调整,并采用高精度的毫秒延期雷管进行微差爆破。实践证明,草楼铁矿采场爆破大块率显著下降,一次爆破的爆破质量有了明显地改善,爆落岩石块度均匀,满足破碎、铲装运输要求,降低了二次爆破率和生产成本,为矿山爆破工程提供了一定的参考。

大直径深孔VCR法拉槽爆破盲炮原因分析及预防措施探讨

自20世纪中期以来,伴随矿山开采的不断增加与间柱采场试验的成功,VCR法也在国内的采矿界得到了广泛应用和普及,并受到了相关人员的高度关注。在VCR采矿法的飞速发展下,其在矿山开采当中的功能与作用也更为凸显,并获得了较好的应用效果,成为了大直径深孔矿山开采中的有效方案,并进一步推动了我国采矿技术的发展。但实践显示,在大直径深孔VCR法拉槽爆破当中,盲炮的情况时有发生,为此,本文结合对其发生原因的分析,进而提出针对性的预防措施。

芍药苷对人胃癌SGC7901/VCR细胞增殖抑制作用及其机制研究

目的:探索芍药苷(paeoniflorin)对人胃癌SGC7901/VCR细胞增殖抑制及凋亡的影响,并研究其可能的分子机制。方法:应用不同浓度芍药苷作用SGC7901/VCR细胞48h后,采用四甲基偶氮唑蓝法(MTT)检测细胞增殖抑制率;流式细胞术(FCM)检测细胞凋亡率;免疫蛋白印迹技术(Western blot)分析Bcl-2、Bax及细胞核内NF-κBp65蛋白的表达;酶联免疫吸附试验(ELISA)进一步确定核内NF-κB的转录活性。结果:芍药苷对SGC7901/VCR细胞生长有明显的抑制作用并促进其凋亡,这种作用呈现剂量依赖性;Westernblot和ELISA均证实芍药苷对NF-κB有明确抑制作用;随着芍药苷浓度增加NF-κB和Bcl-2表达水平逐渐下调(P<0.01),但对Bax没有明显影响。结论:芍药苷可明显抑制SGC7901/VCR细胞的增殖,诱导其凋亡;其机制部分可能与阻断NF-κB通路所介导的Bcl-2分子上调有关。

中药复方君子汤联合环孢霉素A逆转白血病细胞株K562/VCR耐药性的实验研究

本研究观察中药复方君子汤(FFJZ)联合环孢霉素A(cyclosporine A,CsA)逆转白血病耐药细胞系K562/VCR细胞耐药性的效果,以便寻找有效的联合逆转剂。采用MTT法、流式细胞术研究FFJZ联合CsA逆转白血病耐药细胞系K562/VCR耐药性的作用。结果表明:FFJZ联合CsA在体外对K562/VCR细胞的耐药性有明显的逆转作用(p<0.01),能提高K562/VCR细胞对阿霉素(ADM)的敏感性,且在药物有效浓度范围内对细胞本身无毒性作用。FFJZ联合CsA对K562/VCR细胞的P-gp表达的阳性率无明显影响。结论:复方君子汤联合环孢霉素A可能成为治疗白血病多药耐药的安全有效的耐药逆转药物。

RAID-VCR:一种能够承受三个磁盘故障的RAID结构

提出了一种新RAID结构———RAIDVCR.这种结构仅需要3个额外的磁盘来保存校验信息,但是却能够承受任意模式的3个成员磁盘故障.与现有的其它RAID结构相比,RAIDVCR的容灾能力大幅提高,但是对磁盘空间利用率和系统吞吐量的影响却非常小.RAIDVCR的编码和解码过程都是基于简单的XOR操作,并且以明文方式保存了用户数据,从而可以高效地执行读操作.仿真实验结果表明,RAIDVCR的编码和解码性能较好,具有很好的应用前景.

HL-60/VCR多药耐药细胞株耐药机制的研究

背景与目的:白血病细胞对化疗药物的耐药是白血病治疗失败的主要原因,多药耐药细胞株为白血病多药耐药机制和逆转多药耐药性的研究提供了良好的模型。为探讨药物诱导产生多药耐药机制,我们对HL-60/VCR细胞的耐药机制进行了研究。方法:应用流式细胞术和一组抗体,对药物敏感细胞株HL-60和多药耐药细胞株HL-60/VCR细胞的耐药相关蛋白P-gp、MRP、LRP、BCRP、GST-π,以及凋亡调节蛋白bcl-2、bax、bcl-x、bad的表达进行分析。结果:在HL-60/VCR细胞株中,耐药相关蛋白P-gp、MRP、BCRP、GST-π分别是其在HL-60细胞株中的18.62、1.19、1.50、1.32倍,而LRP无变化。凋亡抑制蛋白bcl-2、bcl-x分别是其在HL-60细胞株中的2.48、1.25倍,凋亡调节蛋白bad是HL-60细胞株中的1.08倍;而凋亡诱导蛋白bax反而降低,是HL-60细胞株中的0.88倍。结论:多种机制参与HL-60/VCR的多药耐药,涉及耐药蛋白P-gp、MRP、BCRP和GST-π的表达增强,而且凋亡调节蛋白bcl-2、bax、bcl-x、bad均可能参与其耐药机制的形成。

siRNA对SGC7901/VCR细胞mdr1基因沉默效果的影响因素分析

目的分析siRNA沉默人胃癌SGC7901/VCR细胞mdr1基因效果的相关因素。方法设计并体外转录合成4条靶向mdr1的siRNA(mdr1si326、mdr1si1513、mdr1si2631和mdr1si3071),转染SGC7901/VCR细胞,用RTPCR和免疫印迹检测mdr1mRNA和Pgp的表达、流式细胞仪检测细胞内阿霉素的蓄积和MTT法检测细胞对阿霉素的敏感性,综合这4方面结果评价4条siRNA的沉默效果情况;用分子生物学软分析siRNA沉默效果的影响因素。结果沉默效果最好的mdr1si326和较好的mdr1si2631靶序列编码Pgp的跨膜区而且自身无茎和袢;沉默效果较差的mdr1si3071和最差的mdr1si1513靶序列编码Pgp的胞内区,前者自身成茎和成袢。沉默效果最好的mdr1si326和较好的mdr1si2631靶序列在靶位点和靶位点外间有较少的碱基配对和氢键。siRNA的沉默效果与siRNA3’5’端3个碱基中的A/U数量、N1和N19、GC含量间无规律可循。结论siRNA沉默SGC7901/VCR细胞mdr1的效果与靶序列的结构关系密切。

瑞香狼毒小鼠药物血清增敏化疗药物对K562/VCR耐药细胞的抗癌活性

目的 :研究瑞香狼毒 (SC)小鼠药物血清与细胞毒化疗药物联合应用对K5 6 2 /VCR多药耐药细胞的协同抗肿瘤效应。方法 :小鼠口服SC水提物 6g·kg-1,2h后采集血清。SC药物血清与长春新碱 (VCR)、阿霉素 (Dox)或足叶乙甙 (VP - 16 )联合处理K5 6 2 /VCR多药耐药细胞 ,检测细胞MTT转化率 ,克隆形成和DNA合成能力。结果 :5 %SC药物血清显著增加细胞毒化疗药物对K5 6 2 /VCR耐药细胞的敏感性 ;VCR、Dox、VP - 16对K5 6 2 /VCR的IC50 较单独化疗药物组分别减小 6 .3、15 .0和 18.5倍 ;细胞克隆数分别减少 45 .1%、6 6 .6 %和 5 8.6 % ;[3 H]TdR掺入K5 6 2 /VCR细胞DNA也显著减少。增敏作用随SC药物血清比例的增高而增强。结论