Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex.

Purpose: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule. The poor bioavailability of the capsule formulation may have limited responses in clinical trials, and the large capsules are not suitable for young children. To support the hypothesis that a novel organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB formulation was delivered to mice.

A fluorescence microplate cytotoxicity assay with a 4-log dynamic range that identifies synergistic drug combinations.

Purpose: Cytotoxicity assays in 96-well tissue culture plates allow rapid sample handling for multicondition experiments but have a limited dynamic range. Using DIMSCAN, a fluorescence digital image system for quantifying relative cell numbers in tissue culture plates, we have developed a 96-well cytotoxicity assay with a >4-log dynamic range.

Methods: To overcome background fluorescence that limits detection of viable cells with fluorescein diacetate, we used 2'4'5'6'-tetrabromofluorescein (eosin Y) to quench background fluorescence in the medium and in nonviable cells to enhance the reduction of background fluorescence achieved with digital image thresholding.

External beam radiotherapy and high-dose brachytherapy combined with cisplatin and paclitaxel in patients with advanced cervical carcinoma.

Objective: The aim of the present study was to evaluate toxicity and efficacy of concurrent chemoradiation with cisplatin and paclitaxel and high-dose rate (HDR) brachytherapy in patients with locally advanced cervical cancer.

Patients And Methods: 19 patients with locally advanced cervical carcinoma were treated with external beam radiotherapy (EBRT) to the pelvis +/- paraaortic nodes, HDR brachytherapy, cisplatin at doses of 50 mg/m2 in weeks 1 and 4, and weekly paclitaxel at 50 mg/m2 in weeks 1-5 during years 2000-2002. Chemotherapy was administered until leukopenia < or = 2500/mm3, thrombocytopenia <100,000/mm3, and/or hemoglobin level <100 g/l occurred.

DIMSCAN: a microcomputer fluorescence-based cytotoxicity assay for preclinical testing of combination chemotherapy.

DIMSCAN is a semiautomatic fluorescence-based digital image microscopy system that quantifies relative total (using a DNA stain) or viable (using fluorescein diacetate [FDA]) cell numbers in tissue culture multiwell plates ranging from 6 to 384 wells per plate. DIMSCAN is a rapid and efficient tool for conducting in vitro cytotoxicity assays across a 4 log dynamic range. The specificity of detecting viable cells with FDA is achieved by using digital image processing and chemical quenching of fluorescence in nonviable cells with eosin Y.

Liquid chromatography method for quantifying N-(4-hydroxyphenyl)retinamide and N-(4-methoxyphenyl)retinamide in tissues.

A simple and accurate high-performance liquid chromatography (HPLC) method was developed to measure levels of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its main metabolite N-(4-methoxyphenyl)retinamide (4-MPR) in tissue. Following ultrasonic extraction of fresh tissue in acetonitrile (ACN), 4-HPR and 4-MPR were measured by HPLC with UV absorbance detection at 340 nm, using isocratic elution with ACN, H(2)O, and acetic acid. N-(4-ethoxyphenyl)retinamide (4-EPR) was employed as an internal standard.