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PURPOSE WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is a chemoprotective agent that is currently in pediatric clinical trials. It is a prodrug that is dephosphorylated by alkaline phosphatase to the active free thiol form, WR-1065 [S-2-(3-aminopropylamino)ethanethiol]. It is likely that adequate and sustained cellular levels of the drug are(More)
PURPOSE Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug(More)
The reactions of cisplatin [cis-diamminedichloroplatinum(II), CDDP] with glutathione (GSH) and drug thiols were investigated at 37 degrees C in 100 mM Tris-NO(3), pH approximately 7.4, using a clinically relevant concentration of CDDP (33 micro M), a large excess of GSH (16.5 mM), and [NaCl] of 4.62 mM. The conditions were designed to mimic passage of CDDP(More)
BACKGROUND The aims of this study were to assess the seroprevalence of vaccine-preventable infections in Emirati medical students, and to provide scientific evidence for implementation of a cost-effective immunization guideline and policy for medical school admission. METHODS This prospective cohort study involved 261 (61% female) Emirati medical students(More)
The binding of cisplatin to metallothionein (MT) was investigated at 37 degrees C in 10 mM Tris-NO3 (pH approximately 7.4) and 4.62 mM NaCl. The conditions were chosen to mimic passage of clinical concentrations of cisplatin through the cytosol. The reactions were monitored by high-performance liquid chromatography (HPLC), atomic absorption spectroscopy,(More)
PURPOSE Previous WR-2721 human pharmacokinetic studies were limited to plasma levels in patients receiving platinum-based compounds, and none includes the effects of WR-2721 on endogenous thiols. In the present study (Pediatric Oncology Group study no. 9457), we measured the levels of WR-2721, its active metabolites, as well as cysteine and glutathione in(More)
The Pediatric Oncology Group study for metastatic Ewing's sarcoma used amifostine and mesna with the alkylating agents. To determine the fate of combined drug thiols, we measured thiol levels in plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC) of four patients. We also conducted analogous measurements on two patients who received(More)
INTRODUCTION A novel in vitro system was developed to measure O₂ consumption by murine tissues over several hours. METHODS Tissue specimens (7-35 mg) excised from male Balb/c mice were immediately immersed in ice-cold Krebs-Henseleit buffer, saturated with 95% O₂:5% CO₂. The specimens were incubated at 37 °C in the buffer, continuously gassed with O₂:CO₂(More)
Accurate measurements of dissolved O(2) as a function of time have numerous chemical and biological applications. The Pd (II) complex of meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin (Pd phosphor) was used for this purpose. Detection is based on the principle that the phosphorescence of this oxygen probe is inversely related to dissolved O(2) (O(2)(More)
PURPOSE This Phase I study was designed primarily to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of irinotecan and cisplatin with and without amifostine in children with refractory solid tumors. PATIENTS AND METHODS Cisplatin, at a fixed dose of 30 mg/m(2), and escalating doses of irinotecan (starting dose, 40 mg/m(2))(More)