By Kevin J. Barnham, Susan J. Berners-Price, Zijian Guo, Piedad del Socorro Murdoch (auth.), H. M. Pinedo, J. H. Schornagel (eds.)

Synthesis and task of Platinum Compounds: NMR Spectroscopy of Platinum medicines: From DNA to physique Fluids (K.J. Barnham et al.). Transdiamminedichloroplatinum (II) isn't an Antitumor Drug: Why? (R. Dalbiès et al.). Iminoethers as provider Ligands: a singular Transplatinum complicated owning in Vitro and in Vivo Antitumor job (M. Coluccia et al.). Molecular Dynamics Simulations on Cisplatin Adducts with Dinucleotides (J. Kozelka). Orally energetic DACHPt (IV) Compounds (Y. Kidani et al.). scientific Pharmacology: Pharmacokinetic-Pharmacodynamic Relationships (P. Canal, E. Chatelut). medical Pharmacology of Carboplatin Administered in Alternating series with Paclitaxel in sufferers with Nonsmall mobile Lung melanoma: a ecu melanoma Centre (ECC) research (L.J.C. van Warmerdam et al.). The scientific improvement of the Oral Platinum Anticancer Agent JM216 (I. Judson et al.). Biochemistry and Molecular Pharmacology: Membrane Transportof Platinum Compounds (G. Los et al.). Detection of Adducts shaped upon remedy of DNA with Cisplatin and Carboplatin (A.M.J. FichtingerSchepman et al.). Detection of Platinum Lesions on the Nucleotide point in Cells utilizing unmarried Strand Ligation PCR (J.A. Hartley et al.). A evaluate of the Modulation ofCisplatin Toxicities via Chemoprotectants (R.T. Dorr). CombinationTherapy with Cisplatinum and EGF Receptor Blockade (J. Mendelsohnet al.). medical stories: Oxaliplatin: replace on an Activeand secure Dach Platinum complicated (P. Soulié et al.). blend of alternative Platinum Compounds: matters, techniques and adventure (F.M. Muggia). section I and II experiences with Lobaplatin (H. Fiebig). part I Trials of Ormaplatin (NSC 363812)(M.C. Christian). 254S, NK121 and TRK710 (M. Ogawa). medical Trials of Oxaliplatin and DWA2114R (T. Taguchi). Incorporating checks of Sequencedependence in Developmental reviews of CombinationChemotherapy Regimens Containing New brokers and Platinum Compounds (E.K. Rowinsky). evaluate of Carboplatinbased Highdose Chemotherapy combos within the Autotransplant Setting(S. Rodenhuis et al.). remedy Intensification in Germcell Tumors (J.P. Droz et al.). Nonplatinum steel Complexes: review of Tumorinhibiting Nonplatinum Complexes (B.K. Keppler, E.A. Vogel). Phenotypic elements of Platinum Resistance (T. Fojo et al.). How Does Platinum Kill the phone? The Cisplatininduced mobile harm reaction (S.B. Howell et al.). Controversy consultation: Cisplatin vs. Carboplatin? Carboplatinvs. Cisplatin within the Chemotherapy of reliable Tumors: Procarboplatin (D.S. Alberts). Cisplatin and Carboplatin in Testis and Ovarian melanoma: Procisplatin (S.D. Williams). Resistance: allergic reaction to Cisplatin in Mouse LeukemiaL1210/0 Cells: An XPG DNA fix illness (R. wooden et al.). four extra articles. Index.

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USA, 47: 950-955 (1961). 35 MOLECULAR DYNAMICS SIMULATIONS OF CISPLATIN ADDUCTS WITH DINUCLEOTIDES Jifi Kozelka Laboratoire de Chimie et Biochimie Phannacologiques et Toxicologiques, URA 400 CNRS, Universite Rene Descartes, 45 rue des Saints-Peres, 75270 Paris 06, France INTRODUCTION Whereas the molecular basis for the antitumor activity of cisplatin is not yet established, there are numerous experimental results implicating DNA binding in the antitumor mechanism. Whatever happens between platinum binding to DNA and the cell death, the hypothesis that the structural distortion plays a role in the processing of the Pt-DNA adducts does not seem unlikely, and provides the pharmacological motivation for structural studies on these adducts.

INTRODUCTION Research of relationships between pharmacokinetics and pharmacodynamics in clinical oncology should result in a better use of anticancer drugs. The goal ofthese approaches is to improve cancer chemotherapy by optimising drug therapy in individual patients. After some recalls about general principles of pharmacokinetics and pharmacodynamics, the different models used for analysing pharmacokinetics-pharmacodynamics relationships will be defined. Before considering the different methods of adaptive dosing of anticancer drugs, the different reasons of variability in pharmacokinetics will be described briefly.

Leng, Rearrangement of the 1,3-intrastrand crosslinks into interstrand cross-links in transplatinum-modified DNA (submitted for publication). M. A. Lemaire, A. Schwartz, A. R. Rahmouni, and M. Leng, Interstrand cross-links are preferentially formed at the d(GC) sites in the reaction between eisdiamminedichloroplatinum(l1) and DNA, Proc. Natl Acad Sei. U. S. A. 88: 1982 (1991). U. Belluco, Substitution reactions, in "Organometallic and coordination Chemistry of Platinum", Academic Press, London (1974).

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