Endovascular lung perfusion using high-dose cisplatin: uptake and DNA adduct formation in an animal model.

Mean survival after diagnosis of unresectable pulmonary metastases is less than one year. Isolated lung perfusion (ILP) is a technique that delivers chemotherapy into the pulmonary artery via a thoracotomy. Human trials are limited.

Phase II study of docetaxel and irinotecan in metastatic or recurrent esophageal cancer: a preliminary report.

The outcomes for patients with metastatic or recurrent esophageal cancer are dismal, with 1-year survival rates of approximately 20%. In this phase II study, we studied the combination of docetaxel (Taxotere) and irinotecan (CPT-11, Camptosar) in patients with metastatic or recurrent esophageal cancer. Eligible patients included those with histologic or cytologic diagnosis of adenocarcinoma or squamous cancer of the esophagus or gastroesophageal junction who had received no previous chemotherapy for metastatic esophageal cancer.

Genetic basis of drug metabolism.

The application of pharmacogenetics in identifying single nucleotide polymorphisms (SNPs) in DNA sequences that cause clinically significant alterations in drug-metabolizing enzyme activities is discussed. Recent advances in pharmacogenomic research have begun to elucidate the inherited nature of interindividual differences in drug-induced adverse reactions, toxicity, and therapeutic responses. In one particular area of study, variations in DNA sequences (i.

Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan.

The prodrug irinotecan is an active agent for the treatment of advanced colorectal cancer and a number of other solid tumors. Irinotecan is converted in vivo to SN-38 (7-ethyl-10-hydroxy-camptothecin), the active metabolite that causes cell death, by human liver carboxylesterases. Previous studies suggest that human carboxylesterase 2 (CES2) is the key activating isoform.

Adaptive immunity cooperates with liposomal all-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia.

We previously developed a murine model of acute promyelocytic leukemia (APL) by using human cathepsin G gene regulatory elements to direct the expression of promyelocytic leukemia (PML)/retinoic acid receptor alpha (RAR alpha) and RAR alpha/PML fusion cDNAs to the early myeloid compartment of transgenic mice. To study the efficacy of noncytotoxic therapy in this animal model, cohorts of naive immunocompetent mice were inoculated with primary murine APL cells from a frozen tumor bank. Arsenic trioxide and liposomally encapsulated all-trans-retinoic acid (Lipo ATRA), alone or in combination, were administered for 21 days by i.

Pharmacokinetic study of infusional valspodar.

The pharmacokinetics of valspodar (PSC 833), a selective second-generation P-glycoprotein modulator, was evaluated as part of a Phase I study to modulate paclitaxel therapy in 15 patients with refractory malignancies. Valspodar was given intravenously at 1.42 mg/kg/h for 2 hours, followed by a 27-hour continuous infusion at 0.