John M Hartley

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The single cell gel electrophoresis comet assay has become established as a sensitive technique for measuring DNA strand breaks. The technique has been modified to allow the sensitive detection and quantitation of DNA interstrand cross-linking at the single cell level. Cells are irradiated immediately before analysis to deliver a fixed level of random(More)
Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM) were 19, 6, 10, 7 and 8% of dose respectively. The(More)
Ifosfamide is an oxazophosphorine widely used in the treatment of cancer in children and adults. Nephrotoxicity and neurotoxicity are major side effects. The aim of this study was to use high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of urine to identify novel biochemical markers of ifosfamide-induced toxicity. Urine samples were(More)
In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21-day cycles, which alternated between 3 g m(-2) x (2 or 3) days given as a 1-h bolus doses, or the same total dose as a continuous infusion. Patients who received four or more cycles also alternated between two cycles on dexamethasone 4 mg 8 hourly for 3 days starting 8 h before(More)
DNA damaging agents have been widely used in cancer chemotherapy for many years and have proved successful in the treatment of both solid tissue and haematological malignancies. Many commonly used clinical agents, such as members of the nitrogen mustard, chloroethylnitrosourea, dimethane-sulphonate and platinum classes, are bifunctional. DNA interstrand(More)
Fifteen human glioma cell lines were examined for their sensitivity to 1,3-bis(chloroethyl)-nitrosourea (BCNU, carmustine) and cis-dichlorodiamminoplatinum (cisplatin), the induction of DNA interstrand cross-linking (DNA-ISC) induced by the two agents and cellular O6-alkylguanine alkyltransferase (ATase) activity. Cell lines differed in their sensitivities(More)
A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic(More)
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