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101.
喜树果中喜树碱和10-羟基喜树碱的HPLC分析 总被引:6,自引:0,他引:6
目的:建立测定喜树果中喜树碱和10-羟基喜树碱的反相高效液相色谱法,并用该方法测定9个产地喜树果中喜树碱和10-羟基喜树碱的含量。方法:以Hypersil ODS(250 mm×4.0 mm,5.0 μm)为色谱柱;流动相A为水,B为甲醇;梯度洗脱:在0 min到40 min内流动相由A—B(60:40)到A—B(30:70);流速为1.0 mL·min~(-1);检测波长为254 nm;柱温为25℃。结果:喜树碱在0.10—1.00μg范围内线性关系良好,其低、中、高3个量的平均加样回收率分别为99.66%,100.3%,99.97%;RSD分别为0.57%,0.25%,0.43%。10-羟基喜树碱在0.30-4.00μg范围内线性关系良好,其低、中、高3个量的平均加样回收率分别为99.87%,99.98%,100.4%;RSD分别为0.32%,0.19%,0.34%。结论:该方法是一种灵敏、准确的分析法。 相似文献
102.
目的:应用多元曲线分辨-交替最小二乘(MCR-AIS)法,对7-乙基-10-羟基喜树碱与喜树碱的色谱重叠峰进行分辨,并对杂质喜树碱进行定量。方法:以渐进因子分析(EFA)解析结果作为初始值对喜树碱与7-乙基-10-羟基喜树碱的色谱重叠峰进行ALS迭代优化,直至收敛。结果:采用此方法分辨所得光谱还原率高,定量结果的浓度值与真实值之间线性关系良好。结论:本方法用于药物色谱重叠峰分辨结果可靠。 相似文献
103.
植物来源抗肿瘤药物研究进展 总被引:12,自引:0,他引:12
植物来源抗肿瘤药物乃当今抗肿瘤药物市场上的主角。随着科学技术的不断发展和分子生物学的兴起,对已发现的植物来源抗肿瘤药物的作用机制的认识也日渐深入。为满足抗肿瘤药物市场的需要,通过化学结构的修饰与改造,获得了毒性低而抗肿瘤作用显著的新衍生物;而通过药用植物生物技术与生化工程,大规模生产植物来源抗肿瘤药物亦取得突飞猛进的发展。此外,由于新的筛选方法的建立,新的植物来源抗肿瘤药物及其先导化合物也在不断涌现。着重介绍了目前几种植物来源主流抗肿瘤药物的研究情况及最新进展,包括作用机制、构效关系、结构修饰与改造、生物技术应用等。 相似文献
104.
105.
C. Sessa J. Wanders M. Roelvink P. Dombernowsky D. Nielsen R. Morant P. Drings P. Wissel A.-R. Hanauske 《Annals of oncology》2000,11(2):207-210
Background:GI147211, a 10,11-ethylenedioxy substituted analogueof camptothecin (CPT), was brought into clinical development because of itshigher water solubility and greater potency as compared to topotecan (TPT).The antitumor activity of GI147211 as second-line therapy in small-cell lungcancer (SCLC) was assessed after stratification of patients in refractory (noresponse to initial treatment or relapse within three months from last cycle)and chemosensitive (relapse more than three months from last cycle).
Patients and methods:Sixty-seven patients were entered in thestudy and sixty-two were evaluable for response, twenty-eight in therefractory and thirty-four in the chemosensitive group. All patients hadreceived 1 line of chemotherapy; radiation had also been given in 29 cases,6 in the refractory and 23 in the chemosensitive group. GI147211 wasadministered at 1.2 mg/m2/day as 30-min infusion for fiveconsecutive days every three weeks.
Results:The overall response rate was 16.6% (11 of 66patients; 95% confidence interval (95% CI):8.5%–27.5%), 10.3% (3 of 29 patients; 95%CI: 2.2%–27%) in the refractory and 21.1% (8 of 37patients; 95% CI: 9.5%–37%) in the chemosensitivegroup. Only partial responses (PR) were observed with a median duration of PRof 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitivegroup). Hematological toxicity consisted mainly of neutropenia (grades3–4 in 25% of cycles) and thrombocytopenia (grades 3–4 in23% of cycles); non-hematological toxicity was mild to moderate andconsisted of nausea (22% of cycles), vomiting (11%), malaise(34%).
Conclusions:At the dose and schedule tested GI147211 is an activenew agent for second-line treatment of SCLC; the antitumor activity andtoxicity profile are comparable to those observed with TPT which remains theleading CPT analogue for salvage treatment. Interest has been renewed in theclinical development of GI147211 by preclinical data with the liposomalformulation showing an increased therapeutic index. 相似文献
106.
Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis 总被引:2,自引:0,他引:2
We have previously shown that the androgen-independent prostate cancer cells DU145, despite expressing Fas and FasL, were resistant to anti-Fas-induced apoptosis, and that this resistance could be overcome by pretreating the cells with sublethal doses of camptothecin. Here, we provide evidence that SAPK/JNK activity is required for camptothecin sensitization to anti-Fas-induced apoptosis. Camptothecin, but not Fas ligation, was shown to activate SAPK/JNK in a time-dependent manner, and to induce c-Jun expression. The effects were more prominent in cells treated with both camptothecin and anti-Fas. The expression levels of MKP-1, a phosphatase which regulates SAPK/JNK and which has been implicated in prostate cancer resistance to apoptosis, remained unchanged. Inhibition of caspases had no effect on the SAPK/JNK activation, suggesting that this activation is an upstream event in the Fas-signalling pathway, and is independent of caspase activity. Antisense oligonucleotides targeted to JNK1 and JNK2 reversed the effect of camptothecin. These results suggest that stress kinase activation can significantly influence the fate of androgen-independent prostate cancer cells following Fas receptor ligation. 相似文献
107.
Wachters FM Groen HJ Maring JG Gietema JA Porro M Dumez H de Vries EG van Oosterom AT 《British journal of cancer》2004,90(12):2261-2267
In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked to a water-soluble polymer. Preclinical experiments showed enhanced antitumour efficacy and limited toxicity compared to camptothecin alone. Prior phase I trials guided the regimen used in this study. The objectives were to determine the maximum tolerated dose, dose-limiting toxicities, safety profile, and pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT intravenously administered weekly for 3 weeks in 4-week cycles. At the starting dose level (80 mg x m(-2) week(-1)), no dose-limiting toxicities occurred during the first cycle (n=3). Subsequently, three patients were enrolled at the second dose level (120 mg x m(-2) week(-1)). Two of three patients at the 80 mg x m(-2) week(-1) cohort developed haemorrhagic cystitis (grade 1/3 dysuria and grade 2/3 haematuria) during the second and third cycles. Next, the 80 mg x m(-2) week(-1) cohort was enlarged to a total of six patients. One other patient at this dose level experienced grade 1 haematuria. At 120 mg x m(-2) week(-1), grade 1 bladder toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg x m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg x m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin excretion, associated with bladder toxicity. Due to cumulative bladder toxicity, weekly MAG-CPT is not a suitable regimen for treatment of patients with solid tumours. 相似文献
108.
Werner syndrome (WS) is an autosomal recessive progeroid disease characterized by genomic instability. WRN gene encodes one of the RecQ helicase family proteins, WRN, which has ATPase, helicase, exonuclease and single stranded DNA annealing activities. There is accumulating evidence suggesting that WRN contributes to the maintenance of genomic integrity through its involvement in DNA repair, replication and recombination. The role of WRN in these pathways can be modulated by its post-translational modifications in response to DNA damage. Here, we review the functional consequences of post-translational modifications on WRN as well as specific DNA repair pathways where WRN is involved and discuss how these modifications affect DNA repair pathways. 相似文献
109.
NF-kappaB activation by double-strand breaks 总被引:2,自引:0,他引:2
110.
Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer 总被引:2,自引:0,他引:2
Chedid S Rivera E Frye DK Ibrahim N Esteva F Valero V Hortobagyi G Mettinger KL Cristofanilli M 《Cancer chemotherapy and pharmacology》2006,57(4):540-544
Purpose: The purpose of this phase II study was to evaluate the efficacy and tolerability of Orathecin, an oral camptothecin analog
that has exhibited antitumor activity in breast cancer patients during preclinical studies. Methods: Sixteen patients with metastatic breast cancer previously treated with anthracycline and taxane were utilized in the study.
Orathecin was administered orally at 1.5 mg/m2 /day for the first five consecutive days of the cycle followed by 2 days of rest on a 7-day schedule. The end points of the
study were efficacy and toxicity. Results: The median age of the patients was 51 years (range, 35–73). Eight patients (50%) had multiple disease sites, and nine patients
(56%) received more than three chemotherapy regimens. All patients were evaluated for toxicity, three patients were removed
from the study for toxicity or disease progression prior to 8 weeks and were thus not evaluated for efficacy. The median follow-up
was 110 days (range, 15–554). There were no responses to treatment. Five of the 13 evaluable patients (38%) had stable disease,
eight (61%) had progressive disease. Most adverse events were mild to moderate in intensity. The median time to progression
(TTP) for evaluable patients was 109 days (range, 56–374 days) (lower 95% C.I., 57 days). The median survival time was 272 days
(lower 95% C.I., 209 days). Conclusions: Orathecin at the dose and regimen used in this study resulted in no objective tumor responses for this heavily pretreated
population. Accurate risk stratification strategies can improve patients‘ selection and contribute to determine the appropriate
benefit of therapies in MBC. 相似文献