In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs

The aim of this study was to develop an in vitro human peripheral lymphocyte micronucleus bioassay involving phytohemagglutinin stimulant for urines containing adriamycin (ADR) and cyclophosphamide (CP). In vitro studies with defined concentrations of ADR, CP, and fresh urine showed that mitotic indices and micronuclei counts/1,000 cells had to be log (X + 1) transformed to be able to use parametric statistics and that a specific micronucleus assay for ADR in the presence of CP and urine for 5–15 ng ADR/mL had been developed. Whereas CP alone could be detected between 196–522 μg/mL, this effect was abolished in the presence of 15 ng ADR/mL. Interdonor variabilities relative to ADR sensitivity and CP linear dynamic range were marked, but intradonor variability was small. The MN bioassay tolerated < 10% urine. Results for urines from nine patients receiving antineoplastic drugs (CP, all; ADR, 3; 5-fluorouracil, 3; methotrexate, 3; vincristine, 4; procarbazine, 1; and megestrol acetate, 1) showed that only 1/3 patients given ADR were detected, and two others not given ADR were positive. All frozen urines from the 12 control subjects and the nine patients exhibited depressed mitotic index, with, however, no control patient urines inducing increased micronuclei. Two patients had urines of undefined genotoxic potential since undepressed mitotic indices were not attainable by dilution. The effects of combination chemotherapy in addition to freezing and storage influences were complex. More research is required to be able to interpret the results. ©1993 Wiley-Liss, Inc.     

综合分析药物性肝损伤9355例

目的探讨引起药物性肝损伤的原因、临床分型和预后。方法以"药物性肝损伤"、"药物性肝病"为关键词,检索2001～2011年中国期刊全文数据库,记录文献中患者性别、年龄、用药种类、临床分型和预后的相关数据进行总结分析。结果 88篇文献记录了9 355例患者性别,其中男性4 737例(50.6%),女性4 548例(49.4%)。平均年龄(42.3±13.1)岁。88篇文献记录了9 355例用药信息,其中中草药1 979例(21.15%)、抗结核药1 898例(20.29%)、抗微生物用药1 135例(12.13%)、解热镇痛用药740例(7.91%)、抗肿瘤药662例(7.07%)等。83篇文献记录8 552例临床分型,其中肝细胞型5 005例(62.73%),胆汁淤积型2 039例(23.84%),混合型1 508例(17.63%)。83篇文献记录了8 748例预后,其中治愈好转8 144例(95.23%),无效、自动出院、恶化及死亡604例(6.90%)。结论国内文献报道药物性肝损伤男女比例相当,导致肝损伤的前5类药物分别为中草药、抗结核药、抗微生物用药、解热镇痛用药、抗肿瘤药,损伤类型以肝细胞型居多,患者大多预后良好。     

Use of chiral liquid chromatography for the evaluation of stereospecificity in the carbonyl reduction of potential benzo[c]fluorene antineoplastics benfluron and dimefluron in various species

Benfluron (B) [5-(2-dimethylaminoethoxy)-7H-benzo[c]fluorene-7-one hydrochloride] is a potential antineoplastic agent. In the organism, B undergoes a rapid phase I biotransformation through oxidative and reductive metabolic pathways. The carbonyl reduction of B leads to reduced benfluron, red-B, this is one of the principal pathways for the deactivation of this compound.The structure of B was modified to suppress its rapid deactivation via the carbonyl reduction on C₇. Dimefluron, D (3,9-dimethoxy-benfluron) is one of the derivatives of B, in which an alternative metabolic pathway (O-desmethylation) prevails over the carbonyl reduction.The goal of this study was to develop HPLC methods enabling chiral separations of the red-B and -D enantiomers. The separation of red-B enantiomers was successful done on a Chiralcel OD-R column (250 mm × 4.6 mm ID, 5 μm) using a mobile phase acetonitrile–1 M NaClO₄ (40:60, v/v). Another mobile phase, methanol–1 M NaClO₄ (75:25, v/v), had to be employed for the sufficient resolution of red-D enantiomers. Flow rate was 0.5 ml min⁻¹ in both cases. Red-B was detected at 340 nm, red-D at 370 nm.The above chiral HPLC methods were used for the study of the biotransformation of B and D in the microsomal fractions of liver homogenates prepared from various species (rat, rabbit, pig, guinea pig, goat and human). The enantiospecificity of the respective carbonyl reductases was evaluated and discussed for both prochiral compounds, B and D.     

2018版《国家基本药物目录》与2019版《世界卫生组织基本药物标准清单》中抗肿瘤药物目录的比较和分析

目的:分析2019版《世界卫生组织基本药物标准清单》中抗肿瘤药物目录的变动情况,并将2018版《国家基本药物目录》与2019版《世界卫生组织基本药物标准清单》中抗肿瘤药物目录的差异性进行比较,并结合我国基本国情和恶性肿瘤流行病学特征,为《国家基本药物目录》中抗肿瘤药物目录的科学调整和完善提供参考和建议.方法:比较两版目...     

Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen

During 1985–1990 the U.S. National Cancer Institute (NCI) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis, and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4–5 years since the NCI screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCI screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials

To estimate the magnitude of benefit of chemotherapy in prolonging survival for patients with metastatic colorectal cancer, a meta-analysis of randomized controlled trial was performed. A systematic search was performed to identify randomized trials comparing chemotherapy with observation or supportive care alone. Trials were assessed for quality of reporting, publication bias and heterogeneity. Relative risks for outcomes from published data were pooled using a random-effects model. Seven trials with 614 patients were included. All trials used fluoropyrimidine-based chemotherapy, through a variety of routes and schedules, including intravenous, intra-portal and hepatic arterial infusion. Compared with the 'no-chemotherapy' arm, chemotherapy significantly reduced 1-year mortality (risk ratio 0.69; 95% confidence interval (CI) 0.60-0.81, P < 0.00001). The mortality at 2 years was not significantly different (risk ratio 0.93; 95% CI 0.87-1.00, P = 0.053). Between-trial comparisons demonstrated benefit with a variety of routes and schedules. Chemotherapy significantly prolongs 1-year survival for patients with metastatic colorectal cancer, and should be offered to those with good performance status.     

肺部霉菌感染与有关因素的分析(附40例病例分析)

对40例应用抗生素、肾上腺皮质激素和抗肿瘤药物治疗过程中诱发肺部霉菌感染的患者进行分析,结果说明:肺部霉菌感染的发生和预后与基础疾病、抗生素使用时间和种数、合并应用皮质激素或抗肿瘤药物等有密切关系。     

地奥心血康胶囊过敏反应1例

本文对常用抗肿瘤药物药代动力学参数及血浓度测定方法的国内研究进展作了概述，为临床合理用药提供参考依据。     

96例抗肿瘤药物的不良反应报告分析

目的了解抗肿瘤药物引起的不良反应,为深入开展药品不良反应监测工作提供依据。方法对我市2005年1月至2008年9月收集的96例抗肿瘤药物的不良反应报告进行回顾性分析。结果氟尿嘧啶引发的不良反应最多见,有29例,占30.2%;消化系统损害最常见。结论临床应重视抗肿瘤药物引起的不良反应,须定期监测与报告,其可为临床治疗提供参考资料,减少或避免药品不良反应的发生。