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NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis.
The data show that NVP-AUY922 is a potent, novel inhibitor of HSP90, acting via several processes (cytostasis, apoptosis, invasion, and angiogenesis) to inhibit tumor growth and metastasis.
Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation
A suite of highly reproducible tumor microplate three-dimensional functional assays are established and validated to enhance the biological relevance of early preclinical cancer studies and increase the translational predictive value of in vitro drug evaluation studies and reduce the need for in vivo studies by more effective triaging of compounds.
The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats.
The results indicate that the major pharmacokinetic differences between Carboplatin and cisplatin relate to their renal handling and their reactivity with macromolecules.
cis-Amminedichloro(2-methylpyridine) platinum(II) (AMD473), a novel sterically hindered platinum complex: in vivo activity, toxicology, and pharmacokinetics in mice.
- F. Raynaud, F. Boxall, +5 authors L. Kèlland
- Medicine, ChemistryClinical cancer research : an official journal of…
- 1 November 1997
It is shown that AMD473, at its maximum tolerated dose of 35-40 mg/kg i.p. administration, produced marked in vivo antitumor activity against a variety of murine (ADJ/PC6 plasmacytoma, L1210 leukemia) and human ovarian carcinoma xenograft models, including several possessing acquired resistance to cisplatin.
BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma
- P. Beale, P. Rogers, F. Boxall, S. Sharp, L. Kèlland
- Biology, MedicineBritish Journal of Cancer
- 1 January 2000
Results suggest that, in human ovarian carcinoma cells, high BCL-2 levels (either naturally occurring or through gene transfection) confers a trend towards sensitivity not resistance to platinum drugs.
A phase I and pharmacology study of an oral platinum complex, JM216: dose-dependent pharmacokinetics with single-dose administration
Clinical studies of divided dose schedules using doses within the range of pharmacokinetic linearity (≤120 mg/m2) are now being investigated and little nonhaematological toxicity was seen at doses associated with myelosuppression and antitumour activity.
Comparative distribution and excretion of carboplatin and cisplatin in mice
- Z. Siddik, Mervyn Jones, F. Boxall, K. Harrap
- Chemistry, MedicineCancer Chemotherapy and Pharmacology
- 1 February 1988
The results indicate that, although there are quantitative differences, the distribution and excretion profiles are similar for Carboplatin and cisplatin, and both the platinum concentrations and tissue-to-plasma ratios were similar.
Biliary Excretion, Renal Handling and Red Cell Uptake of Cisplatin and CBDCA in Animals
Cis-diammine (1,1-cyclobutanedicarboxylato)platinum II (CBDCA, JM8) as a potential alternative to cisplatin in cancer chemotherapy and phase II and III studies are currently in progress.
Flameless atomic absorption spectrophotometric determination of platinum in tissues solubilized in hyamine hydroxide.
The concentrations of platinum in tissues removed from rats 2 h after they had received the antitumor drug Carboplatin were comparable using either of the procedures, indicating the utility of tissue solubilization.
Retention of activity by the new generation platinum agent AMD0473 in four human tumour cell lines possessing acquired resistance to oxaliplatin.
- S. Sharp, C. O'Neill, P. Rogers, F. Boxall, L. Kèlland
- Biology, MedicineEuropean journal of cancer
- 1 November 2002
Data show that acquired resistance to oxaliplatin may occur in cell lines (and therefore probably in the clinic) and in the four independent cell lines studied this was circumvented by AMD0473, and alongside previously described models of acquired Resistance to cisplatin, these oxali Platin-resistant cell line models may be useful in the evaluation of further novel platinum agents.