Biomaterial Database

Cremophor-EL enhances taxol efficacy in a multi-drug resistant C1300 neuroblastoma cell line. 1993

D S Chervinsky, and M L Brecher, and M J Hoelcle

Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, New York 14263.

We have previously developed a homoharringtonine (HHT) resistant murine C1300 neuroblastoma cell line with increased p-glycoprotein expression and cross resistance to Adriamycin. Drug resistance in this cell line was reversed using cyclosporin-A, dipyridamole and cremophor-EL (CRE). Because of the high CRE content of parenteral taxol, we examined the ability of this solvent to reverse taxol cross-resistance in this cell line. Comparative ID-50s using clonogenic assays in agar indicate a 214-fold resistance to HHT. CRE reverses taxol cross-resistance in a dose-dependent manner from 0.003 to 0.1%, and is maximally effective at a subtoxic concentration of 0.03%. High pressure liquid chromatography (HPLC) analysis of taxol treated C1300/HHT cells reveal that CRE causes changes in intracellular drug levels that are not related to drug efflux. Our work shows that clinical preparations of taxol, when diluted to effective doses, contain enough CRE to mitigate multi-drug resistance. Clinical successes of taxol in refractory tumors may be due in part to the ability of its CRE base to reverse multi-drug resistance.

UI	MeSH Term	Description	Entries
D007424	Intracellular Fluid	The fluid inside CELLS.	Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D009447	Neuroblastoma	A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	Neuroblastomas
D002626	Chemistry, Pharmaceutical	Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.	Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D004354	Drug Screening Assays, Antitumor	Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.	Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005990	Glycerol	A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, or sweetening agent.	1,2,3-Propanetriol,Glycerin,1,2,3-Trihydroxypropane,Glycerine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures