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151.
Daniel Schlaifer Eliane Duchayne C cile Demur Paul Alvinerie Catherine Muller Michel Attal Michael R. Cooper Catherine Payen Bernard Monsarrat Charles E. Myers Jacques Prisi Guy Laurent 《Leukemia & lymphoma》1996,20(5):441-446
Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with (3H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts. 相似文献
152.
153.
PDP—PEG2000-DSPE修饰的长春新碱脂质体的制备及其包封率测定 总被引:4,自引:0,他引:4
目的研制载有长春新碱并用PDP-PEG2000-DSPE对脂质体膜修饰的脂质体并且测定其包封率。方法采用薄膜蒸发超声分散法制备长春新碱脂质体,并用PDP-PEG2000-DSPE对脂质体膜修饰。应用激光电位粒度仪Zeta3000,以去离子水为分散介质测定样品的体积平均粒径。以高效液相色谱法测定其含量和包封率。结果长春新碱脂质体的平均体积粒径大约150nm左右,包封率40%。结论薄膜蒸发超声分散法适用于制备长春新碱脂质体;高效液相色谱法操作简单,准确,重复性好,可用于测定长春新碱脂质体的含量和包封率。 相似文献
154.
Song X Zhao Y Wu W Bi Y Cai Z Chen Q Li Y Hou S 《International journal of pharmaceutics》2008,350(1-2):320-329
PLGA nanoparticles simultaneously loaded with vincristine sulfate (VCR) and verapamil hydrochloride (VRP) were prepared via combining O/W emulsion solvent evaporation and salting-out method. Ten independent processing parameters and two materials characteristics were assessed systematically to enhance the incorporation of the two hydrophilic low molecular weight drugs into PLGA nanoparticles and minimize nanoparticles size. Approaches investigated for the enhancement of drug entrapment efficiencies and the minimization of particle size included the influence of the molecular weight (MW) of PLGA and the lactide to glycolide (L:G) ratio of PLGA, PLGA concentration, the degrees of hydrolyzation and polymerization of PVA, PVA concentration, initial VCR and VRP content, acetone to dichloromethane volume ratio, aqueous phase pH, salt concentration of aqueous phase, aqueous to organic phase volume ratio, sonication time, sonication energy and removal rate of organic solvents. The nanoparticles produced by optimal formulation were submicron size (111.4 ± 2.35 nm, n = 3) and of low polydispersity (0.062 ± 0.023, n = 3). Nanoparticles observed by transmission electron microscopy (TEM) showed extremely spherical shape. The entrapment efficiencies determined with high performance liquid chromatogram (HPLC) by ultracentrifuge method were 55.35 ± 4.22% for VCR and 69.47 ± 5.34% for VRP, respectively (n = 3). 相似文献
155.
Cancer patients treated with antimitotic drugs in the taxane and vinca alkaloid classes sometimes develop a chronic painful peripheral neuropathy whose cause is not understood. In animal models of painful peripheral neuropathy due to nerve trauma or diabetes there is obvious axonal degeneration accompanied by an abnormal incidence of spontaneous discharge in A-fiber and C-fiber nociceptors. But animals with paclitaxel- and vincristine-evoked neuropathic pain do not have axonal degeneration at the level of the peripheral nerve. However, recent data show that they do have a partial degeneration of the primary afferent neurons’ terminal arbors in the epidermis. It is not clear as to whether this relatively minor degeneration is accompanied by abnormal spontaneous discharge. We surveyed primary afferent axonal activity in the sural nerve of rats with the paclitaxel- and vincristine-evoked pain syndromes at the time of peak pain severity. Compared to vehicle-injected controls, we find a significant increase in spontaneously discharging A-fibers and C-fibers. Moreover, we show that prophylactic treatment with acetyl-l-carnitine (ALC), which blocks the development of the paclitaxel-evoked pain, causes a significant decrease (ca. 50%) in the incidence of A-fibers and C-fibers with spontaneous discharge. These results suggest that abnormal spontaneous afferent discharge is likely to be a factor in the pathogenesis of chemotherapy-evoked painful peripheral neuropathy, and that the therapeutic effects of ALC may be due to the suppression of this discharge. 相似文献
156.
Kristin Frommann Birgit Appl Patrick Hundsdoerfer Konrad Reinshagen Georg Eschenburg 《Journal of pediatric surgery》2018,53(10):2059-2064
Purpose
In spite of good initial therapy response neuroblastomas often spread to distant organs or relapse after periods of remission. Dysregulation of apoptosis, a hallmark of cancer, is often effected by elevated levels of antiapoptotic signals leading to resistance against chemotherapeutic drugs. Inhibitors of apoptosis proteins (IAPs) are crucial cellular apoptosis regulators. Targeting IAPs with Smac mimetics has been demonstrated as a promising strategy for treatment of neuroblastoma and other tumors.Methods
In paired neuroblastoma cell lines, obtained from the same patient at time of diagnosis (CHLA-15) and postchemotherapy during progressive disease (CHLA-20), expression of crucial IAPs was determined. Furthermore, effects of vincristine on viability, cytotoxicity, apoptosis induction and caspase-3/7 activation were determined.Results
Cellular IAP-1 (cIAP-1) and X-linked IAP (XIAP) expression was increased in cell line CHLA-20. Moreover, biological effects of vincristine were significantly lower in these cells. Treatment of cells with Smac mimetic LCL161 increased the effects of vincristine in CHLA-15 cells and more importantly was able to overcome vincristine resistance in CHLA-20 cells.Conclusions
These findings demonstrate the potential of Smac mimetics for the development of novel therapeutic approaches for the treatment of relapsed/resistant neuroblastoma. 相似文献157.
Hofmeister CC Jansak B Denlinger N Kraut EH Benson DM Farag SS 《Leukemia research》2008,32(8):1295-1298
In patients with multiple myeloma, there is preclinical justification to combine arsenic trioxide (ATO and As2O3) with DVd (Doxil™, vincristine, and dexamethasone) for newly diagnosed patients. Eleven patients on this phase II trial received 0.15 mg/kg of ATO for five consecutive days followed by four cycles of DVd plus ATO with the ATO at 0.25 mg/kg IV twice per week. The most common grade 3 toxicities were hyperglycemia, hyponatremia, and hypocalcemia. There were four partial and no complete responses. We could not demonstrate that the addition of ATO with this schedule improved the response rate of MM to DVd. 相似文献
158.
Charles O. Noble Zexiong Guo Mark E. Hayes James D. Marks John W. Park Christopher C. Benz Dmitri B. Kirpotin Daryl C. Drummond 《Cancer chemotherapy and pharmacology》2009,64(4):741-751
Purpose Liposome and immunoliposome formulations of two vinca alkaloids, vincristine and vinblastine, were prepared using intraliposomal triethylammonium sucroseoctasulfate and examined
for their ability to stabilize the drug for targeted drug delivery in vivo.
Methods The pharmacokinetics of both the encapsulated drug (vincristine or vinblastine) and liposomal carrier were examined in Sprague
Dawley rats, and the in vivo drug release rates determined. Anti-HER2 immunoliposomal vincristine was prepared from a human
anti-HER2/neu scFv and studied for targeted cytotoxic activity in cell culture, and antitumor efficacy in vivo.
Results Nanoliposome formulations of vincristine and vinblastine demonstrated similar pharmacokinetic profiles for the liposomal carrier,
but increased clearance for liposome encapsulated vinblastine (t
1/2 = 9.7 h) relative to vincristine (t
1/2 = 18.5 h). Immunoliposome formulations of vincristine targeted to HER2 using an anti-HER2 scFv antibody fragment displayed
a marked enhancement in cytotoxicity when compared to non-targeted liposomal vincristine control; 63- or 253-fold for BT474
and SKBR3 breast cancer cells, respectively. Target-specific activity was also demonstrated in HER2-overexpressing human tumor
xenografts, where the HER2-targeted formulation was significantly more efficacious than either free vincristine or non-targeted
liposomal vincristine.
Conclusions These results demonstrate that active targeting of solid tumors with liposomal formulations of vincristine is possible when
the resulting immunoliposomes are sufficiently stabilized. 相似文献
159.
目的:研究plk1在秋水仙胺和长春新碱抗肿瘤效应中的作用。方法:采用Western blotting和共聚焦显微镜检测秋水仙胺、长春新碱及plk1 反义寡核苷酸(Asodn)处理对K562细胞plk1及γ微管蛋白表达的影响。结果:Western blotting 检测结果提示秋水仙胺和长春新碱不影响plk1和γ微管蛋白的表达量,但共聚焦显微镜观察发现秋水仙胺和长春新碱影响plk1在分裂期聚集和中心体形成。plk1 Asodn处理不仅可明显降低plk1蛋白表达,而且影响γ微管蛋白聚合形成中心体。结论:秋水仙胺和长春新碱抗肿瘤效应可能是通过plk1介导的抑制γ微管蛋白聚合形成中心体来实现的,plk1具有作为肿瘤治疗靶点的可能性。 相似文献
160.
长春新碱载体红细胞天然免疫活性及其分子变化研究 总被引:1,自引:0,他引:1
目的:研究长春新碱(VCR)载体红细胞的天然免疫黏附活性变化,并从分子水平进行深入探讨。方法:改良低渗预膨胀法制备VCR载体红细胞。采用新鲜血天然免疫功能快速测定法和荧光标记流式细胞分析的方法,检测载体制备过程中洗涤、预膨胀和载药各阶段红细胞的天然免疫黏附活性及相关表面分子的变化情况。结果:低渗预膨胀处理的肿瘤患者红细胞,天然免疫黏附能力[黏附率(39.20±18.14)%]明显高于其他对照组(P<0.05)。健康人红细胞载药前后天然免疫黏附能力[黏附率(48.30±13.52)%和(51.20±11.24)%],均明显高于肿瘤患者(P<0.05),但VCR载药对红细胞的天然免疫黏附活性影响不明显。洗涤、低渗预膨胀和载药处理后,红细胞表面CD35、CD44、CD55、CD59等分子有不同程度的下降,CCR4分子呈上升趋势。结论:载药处理对红细胞天然免疫黏附活性无明显影响。 相似文献