Martha E. Linsenmeyer

Learn More
Cremophor EL, a pharmacologically inactive solubilising agent, has been shown to reverse multidrug resistance (MDR). Using flow cytometric evaluation of equilibrium intracellular levels of daunorubicin (DNR), we found that eight other surface active agents will also reverse MDR. All the active detergents contain polyethoxylated moieties but have no(More)
BACKGROUND Paclitaxel (Taxol) is the first of a new class of cytotoxic agents with activity against tumors resistant to other drugs. For clinical use, paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant Cremophor EL (Cremophor). We have previously shown that Cremophor will block the P-glycoprotein drug efflux(More)
A polyethoxylated castor oil, Cremophor EL, which is used as a vehicle for p.o. and i.v. administration of water-insoluble compounds in humans, can reverse the multidrug resistance (MDR) phenotype at doses which are likely to be readily achievable clinically. Using flow cytofluorometric analysis of daunorubicin (DNR) uptake as a measure of the expression of(More)
We have quantitated the levels of mRNAs in bone marrow samples from patients with multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3 (which can also inactivate a wide variety of cytotoxic drugs) and examined the relationship between the levels of(More)
We have investigated the function and sequence specificity of DNA methylation in the hypermethylated CpG island promoter region of the endogenous human LINE-1 (L1) retrotransposon family. In nontransformed human embryonic fibroblasts, inhibition of DNA methylation with 5-azadeoxycytidine induced a greater than 4-fold increase in transcription from(More)
The restriction endonucleases (ENases) BstNI (CCATGG) and EcoRII (CCATGG) both cleave DNA at the same time sequences, but only EcoRII produces 5-nucleotide (nt) cohesive ends and is inhibited by 5-methylation of the inner cytosine. The low-Mr fragments in digests of mouse DNA made with these two ENases exhibit different mobilities during agarose-gel(More)
Mouse ES cells with a null mutation of the known DNA methyltransferase retain some residual DNA methylation and can methylate foreign sequences de novo. We have used bisulfite genomic sequencing to examine the sequence specificity and distributions of methylation of a hypermethylated CG island sequence, mouse A-repeats. There were 13 CG dinucleotides in the(More)
SummaryThe p16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in the p16 gene in(More)
 Docetaxel (Taxotere, Rhone-Poulenc Rorer) and etoposide are water-insoluble drugs formulated with polysorbate 80 for intravenous administration. We have previously reported that surfactants, including polysorbate 80 and Cremophor EL, can reverse the multidrug resistance (MDR) phenotype in an experimental system and that plasma Cremophor EL concentrations(More)
Cremophor EL (cremophor), a component of the paclitaxel formulation, can potentially reverse P-glycoprotein-associated multidrug resistance. A Phase I trial of cremophor as a 6-h infusion every 3 weeks was performed with bolus doxorubicin (50 mg/m2). The cremophor dose was escalated from 1 to 60 ml/m2. A standard paclitaxel premedication was given before(More)