In Vitro and In Vivo Mechanistic Studies toward Understanding the Role of 1-Aminobenzotriazole in Rat Drug-Drug Interactions.

1-Aminobenzotriazole (ABT) is regularly used in vivo as a nonspecific and irreversible cytochrome P450 inhibitor to elucidate the role of metabolism on the pharmacokinetic profile of xenobiotics. However, few reports have considered the recent findings that ABT can alter drug absorption or have investigated the possible differential inhibition of ABT on intestinal and hepatic metabolism. To address these uncertainties, pharmacokinetic studies under well controlled and defined ABT pretreatment conditions (50 mg/kg, 1 hour ABT i.

Seed migration in prostate brachytherapy depends on experience and technique.

Purpose: To determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy.

Methods And Materials: We analyzed the first 495 patients treated in our department. All patients were treated with loose (125)I seeds with automated seed delivery system and real-time intraoperative planning.

Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma.

Background: A direct association between radiotherapy dose, side-effects and secondary cancers has been described in patients with seminoma. A treatment planning study was performed in order to compare computed tomography-based traditional radiotherapy (CT-tRT) versus bone marrow-sparing intensity-modulated radiation therapy (BMS-IMRT) in patients with Stage I seminoma.

Material And Methods: We optimized in 10 patients a CT-tRT and a BMS-IMRT treatment plan to deliver 20 Gy to the para-aortic nodes.

Combined intensity-modulated radiation therapy vs. three-dimensional highly conformal radiotherapy after (125)I prostate permanent seed brachytherapy: a comparative treatment planning study.

Purpose: A comparative treatment planning study was conducted to analyze combined intensity-modulated radiation therapy (IMRT) vs. three-dimensional highly conformal radiotherapy (3D-hCRT) after (125)I permanent seed brachytherapy in patients with localized prostate cancer.

Methods And Materials: We optimized an IMRT and a 3D-hCRT treatment plan to 45Gy in 9 patients 2 months after (125)I seed brachytherapy (110Gy) implant.

Species differences in troxacitabine pharmacokinetics and pharmacodynamics: implications for clinical development.

Purpose: Troxacitabine is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Significant differences in troxacitabine toxicity between mice, rats, monkeys, and humans were observed during preclinical and clinical evaluations. To better understand the different toxicity and efficacy results observed between the human xenograft mouse tumor models used for preclinical assessment and the clinical study results, the pharmacodynamics and pharmacokinetics of troxacitabine were reassessed in murine and human models.

Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents.

A novel series of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes was identified as potent apoptosis inducers through a cell-based high throughput screening assay. Six compounds from this series, MX-58151, MX-58276, MX-76747, MX-116214, MX-116407, and MX-126303, were further profiled and shown to have potent in vitro cytotoxic activity toward proliferating cells only and to interact with tubulin at the colchicine-binding site, thereby inhibiting tubulin polymerization and leading to cell cycle arrest and apoptosis. Furthermore, these compounds were shown to disrupt newly formed capillary tubes in vitro at low nanomolar concentrations.