Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks.

Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks.

Patients And Methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m2/day.

Pharmacological determinants of 9-aminocamptothecin cytotoxicity.

The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currently undergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity against human breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied.

Determination of lovastatin in human plasma using reverse-phase high-performance liquid chromatography with UV detection.

The authors have developed a simple, rapid HPLC assay with ultraviolet (UV) detection for the analytical determination of lovastatin and its acid in human plasma for a concentration range of 100-5,000 ng/mL. Sample clean-up involved the use of C10 solid-phase extraction cartridges. Our limit of quantitation was 100 ng/mL.

Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity.

Salvage of preformed nucleosides requires transport across the plasma membrane by sodium-dependent (concentrative) and sodium-independent (equilibrative) mechanisms. These transport systems are also the route of cellular uptake for nucleoside analogues, including gemcitabine (2',2'-difluorodeoxycytidine), a deoxycytidine analogue used in the treatment of pancreatic cancer. To determine whether gemcitabine cytotoxicity is influenced by the equilibrative-sensitive nucleoside transporter (es-NT), basal levels of the es-NT were quantified in three human pancreatic cancer cell lines (PANC-1, HS-766T, and PK-8) and one human bladder cancer cell line (MGH-U1) by flow cytometric analysis, and the results were compared with gemcitabine cytotoxicity assessed by clonogenic assay.