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31.
目的 探讨FLAG和IA方案对P-gp阳性和阴性急性髓细胞白血病(AML)细胞增生抑制作用的优劣及其机制。方法 流式细胞仪检测K562和K562/A02细胞的P-gp 表达,MTT法检测FLAG和IA方案对K562和K562/A02细胞的增生抑制作用,高效液相色谱法检测细胞内Ara-CTP、Ara-C水平,实时定量PCR检测细胞hENT1基因表达。结果 K562 和K562/A02细胞的P-gp阳性率分别为(1.32±0.24)%和(97.66±3.77)%,两种化疗方案对细胞的P-gp表达无影响。FLAG方案对K562细胞的增生抑制作用较IA方案差[(73.17±13.20)%对(84.41±9.33)%,P <0.05],而对K562/A02细胞的增生抑制作用优于IA方案[(70.55±11.32)%对(48.46±12.81)%,P <0.01]。FLAG方案作用时AML细胞内Ara-CTP、Ara-C水平及人平衡核苷载体(hENT1)基因表达均较IA方案作用时升高(P <0.05)。结论 P-gp阳性AML细胞对FLAG方案较IA方案更敏感。氟达拉滨对Ara-C的生化调节可能是其主要机制。 相似文献
32.
Ufuk Gunduz Tugba Keskin Gulistan Tansık Pelin Mutlu Serap Yalcın Gozde Unsoy Arzu Yakar Rouhollah Khodadust Gungor Gunduz 《Biomedicine & Pharmacotherapy》2014
Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform–infrared spectroscopy (FT–IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0–500 μg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy. 相似文献
33.
目的探讨急性早幼粒细胞白血病(Acute promyelocytic leukemia,APL)患者使用伊达比星进行巩固治疗的效果,分析药物对患者复发率及不良反应的影响。方法选取本院2011年11月~2013年11月收治的急性早幼粒细胞白血病患者60例,根据随机数表法分为两组,每组30例。所有患者均接受相同的诱导治疗及维持治疗,观察组巩固化疗单用伊达比星,对照组巩固化疗则使用吡柔比星+阿糖胞苷。以3个月作为1个治疗周期,对比两组治疗5个周期的疗效、复发率、随访3年无病生存率及不良反应。结果观察组中性粒细胞水平恢复时间及症状完全缓解时间短于对照组,差异均有统计学意义(P0.05);观察组治疗完全缓解率高于对照组,差异有统计学意义(P0.05)。观察组治疗3年后无病生存率高于对照组,差异有统计学意义(P0.05);观察组心脏毒性、消化系统毒性、感染及其他毒副反应发生率均低于对照组,差异有统计学意义(P0.05)。结论急性早幼粒细胞白血病患者接受伊达比星进行巩固化疗利于加快患者各症状及体征快速缓解,近期复发率低,患者近期无病生存情况理想,且不良反应发生情况少,药物使用安全有效。 相似文献
34.
去甲氧柔红霉素治疗急性白血病的疗效分析 总被引:9,自引:2,他引:7
目的:分析和比较去甲氧柔红霉素(DA)和米托蒽酯(MTN)治疗急性白血病的疗效和毒副作用。方法:将92例急性白血病者分为两组,治疗组56例用IDA加阿糖胞苷(Ara-c)治疗,对照组36例用MTN加Ara-c治疗,两组均用标准3+7方案。结果:治疗组和对照组完全缓解率(CR)分别为60.7%和38.9%,总有效率分别为82.1%和61.1%,两组CR率和总有效率差异均有显著性意义(P〈0.05); 相似文献
35.
M. Tolomeo Rosa Alba Gancitano Maurizio Musso Ferdinando Porretto Rosanna Perricone Vincenzo Abbadessa Aurelio Cajozzo 《Cancer chemotherapy and pharmacology》1996,39(1-2):157-161
4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good cytotoxic activity in vitro against tumor
cell lines displaying the multidrug-resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol (2HIDA) and,
in this form, seems to exert its antitumoral activity in vivo. Recent studies have shown that 2HIDA has tumoricidal activity
similar to that of the parent drug when tested in vitro in sensitive neoplastic cells. In this work we compared in vitro the
effects of IDA and 2HIDA used alone and in combination with 2 μM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R and in their sensitive parent cell lines FLC and K562.
IDA and 2HIDA showed the same cytotoxic activity in sensitive cells. After 1 h of exposure of cells to each anthracycline,
we observed that the cellular uptake of IDA and 2HIDA was also similar. In resistant cells, 2HIDA was 3–4 times less active
than IDA. We observed that the intracellular uptake of 2HIDA was lower than that of IDA, and this may be correlated with a
greater ability of P-glycoprotein to expel 2HIDA as opposed to IDA. Indeed, when MDR cells were exposed to IDA and 2HIDA in
combination with 2 μM CyA, the cytotoxic effect of these anthracyclines was the same, and it was similar to that observed in sensitive cells. These
data confirm the utility of the combination of IDA and an MDR-reversing agent in hematological malignancies displaying the
MDR phenotype.
Received 7 April 1995/Accepted 13 May 1996 相似文献
36.
Toshihiro Fukushima Taro Yamashita Nobuyuki Goto Takanori Ueda Ken-ichi Okabe Yasunobu Kuraishi Ryuzo Ohno Akio Urabe Makoto Ogawa 《International journal of hematology》2001,74(3):297-302
To clarify the pharmacokinetic properties of idarubicin (IDA) in Japanese patients and to clarify the relationship between the pharmacokinetic parameters of IDA or idarubicinol (IDAol), an active metabolite of IDA, and leukocytopenia or neutropenia, we examined the pharmacokinetics of IDA in patients with malignant lymphoma. Nine of 21 patients registered in an early phase II study of IDA were enrolled in the pharmacokinetic study. IDA (12 or 15 mg/m2) was administered by intravenous infusion for 5 minutes. The elimination half lives (t 1/2) of IDA were 11.0 hours and 12.5 hours after administration of 12 and 15 mg/m2 IDA, respectively. IDAol appeared rapidly both in plasma and in blood cells, and its concentrations exceeded those of IDA within 4 hours. IDAol had a very long t 1/2 (69.2 hours and 70.0 hours for 12 and 15 mg/m2, respectively). The areas under the concentration curves of IDAol in plasma were 3.4 and 5.8 times higher than those of IDA after administration of 12 and 15 mg/m2 IDA, respectively. The t 1/2 of IDAol in plasma correlated significantly with the nadir of neutrophils, and the steady-state volume of distribution of IDA in plasma and in blood cells correlated significantly with the nadirs of white blood cells and neutrophils. These results suggest that both IDA and IDAol play an important role in leukocytopenia or neutropenia. No substantial differences between Japanese and Caucasian people in the pharmacokinetics of IDA were apparent. 相似文献
37.
Objective: The objectives of the investigations were (1) to determine the binding characteristics of idarubicin (IDA) in human serum
and cell culture solutions, (2) to determine the effect of protein binding on the uptake and retention of IDA by human leukemic
cell lines in culture and the extent to which R-verapamil (R-VRP), an inhibitor of the P-glycoprotein (P-gp) transporter,
can modulate these processes, and (3) to assess the importance of protein binding on cytostatic and chemosensitizer action
in vivo.
Methods: The protein binding of IDA was determined using equilibrium dialysis. Cell uptake of IDA was measured using sensitive and
P-gp-containing resistant human leukemic cell lines (HL-60 and HL-60-Vinc) in vitro. IDA was assayed spectrophotofluorometrically.
Results: In the incubation media examined, the free fraction of IDA varied more than seven-fold from approximately 60% in 15% fetal
calf serum (FCS)/PBS to only 8% in human serum. Cellular uptake of IDA was approximately three times higher in medium containing
low protein concentrations. R-VRP eliminated the difference in IDA uptake between resistant and sensitive cell lines and this
was the case when the cells were incubated in solutions containing both high and low protein concentrations. However, R-VRP
did not overcome the effect of high protein concentrations on IDA uptake.
Conclusions: Plasma protein binding is an important determinant for cellular uptake of IDA in vitro. This should be taken into account
when interpreting results of in vitro functional assays with patient material. Chemosensitizers such as R-VRP are effective
in both high and low protein solutions. Investigations like these may be useful for evaluating cytostatic efficacy and chemosensitizer
action in vivo.
Received: 10 August 1998 / Accepted in revised form: 15 January 1999 相似文献
38.
《Biomedicine & Pharmacotherapy》2014,68(8):1149-1159
Anthracycline chemotherapy is often used in the treatment of various malignancies. Its application, however, encounters several limitations due to development of serious side effects, mainly cardiotoxicity and may be ineffective due to multidrug resistance (MDR). Many different compounds have been evaluated as poorly effective in the protection against anthracycline side effects and in the prevention from MDR. Thus, continuous investigational efforts are necessary to find valuable protectants and the flavonoid quercetin (Q) seems to be a promising candidate. It is present in relatively high amounts in a human diet and the lack of its toxicity, including genotoxicity has been confirmed. The structure of Q favours its high antioxidant activity, the potential to inhibit the activity of oxidative enzymes and to interact with membrane transporter proteins responsible for development of MDR, e.g. P-glycoprotein. Furthermore, Q can influence cellular signalling and gene expression, and thus, alter response to exogenous genotoxicants and oxidative stress in normal cells. It accounts for its chemopreventive and anticancer properties. Overall, these properties might indicate the possibility of application of Q as cardioprotectant during anthracycline chemotherapy. Moreover, numerous biological properties displayed by Q might possibly result in the reversal of MDR in tumour cells and improve the efficacy of chemotherapy. However, these beneficial effects towards anthracycline-induced complications of chemotherapy have to be further explored and confirmed both in animal and clinical studies. Concurrently, investigations aimed at improvement of the bioavailability of Q and further elucidation of its metabolism after application in combination with anthracyclines are needed. 相似文献
39.
Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients. 总被引:2,自引:0,他引:2
We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose-independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39.0 L/h/m2 for idarubicin versus 38.6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) and elimination half-life (42.7 versus 47.4 h). The only metabolites detected were the 13-dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half-life of idarubicinol was two times higher than that of daunorubicinol (80.7 versus 37.3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half-life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin. 相似文献