1.In vivo measurement of platinum in the kidneys using X-ray fluorescence.
Kadhim R1, al-Hussany A, Ali PA, Hancock DA, el-Sharkawi AM. Ann N Y Acad Sci. 2000 May;904:263-6.
A noninvasive in vivo method has been developed and optimized for measuring platinum concentrations in the kidneys of patients receiving chemotherapy. The method is based on polarizing the X-ray beam from an orthovoltage radiotherapy treatment unit, the Pantak DXT-300, and using the beam to produce emission of the characteristic platinum X-rays from the kidney. The platinum is derived from platinum-based chemotherapy drugs, such as cisplatin and its analogues (carboplatin and iproplatin), used to treat cancer patients. The clinical motivation for measuring the platinum concentration in both the kidneys and the tumor is to optimize the treatment by establishing the relationships between the accumulation of the drug at those sites. Such clinical information could be valuable in maximizing the therapeutic ratio toward the tumor tissue and limiting the hazards to the kidney. The performance of the system was experimentally optimized with respect to the applied X-ray tube voltage, filter material, and polarizer.
2.[About side effects of platinum drugs].
Waszkiewicz K1. Postepy Hig Med Dosw. 2001;55(3):387-406.
The work presents current view about toxic effects of platinum anticancer drugs. In the first part, the toxic effects of cisplatin as nephrotoxicity, ototoxicity, myelosuppression, anaphylactic-like reactions, neurotoxicity and gastrotoxicity are presented. The second part describes mechanisms of nephrotoxicity of cisplatin. In the third part, the toxicity of carboplatin and iproplatin are reviewed.
3.Consensus-phenotype integration of transcriptomic and metabolomic data implies a role for metabolism in the chemosensitivity of tumour cells.
Cavill R1, Kamburov A, Ellis JK, Athersuch TJ, Blagrove MS, Herwig R, Ebbels TM, Keun HC. PLoS Comput Biol. 2011 Mar;7(3):e1001113. doi: 10.1371/journal.pcbi.1001113. Epub 2011 Mar 31.
Using transcriptomic and metabolomic measurements from the NCI60 cell line panel, together with a novel approach to integration of molecular profile data, we show that the biochemical pathways associated with tumour cell chemosensitivity to platinum-based drugs are highly coincident, i.e. they describe a consensus phenotype. Direct integration of metabolome and transcriptome data at the point of pathway analysis improved the detection of consensus pathways by 76%, and revealed associations between platinum sensitivity and several metabolic pathways that were not visible from transcriptome analysis alone. These pathways included the TCA cycle and pyruvate metabolism, lipoprotein uptake and nucleotide synthesis by both salvage and de novo pathways. Extending the approach across a wide panel of chemotherapeutics, we confirmed the specificity of the metabolic pathway associations to platinum sensitivity. We conclude that metabolic phenotyping could play a role in predicting response to platinum chemotherapy and that consensus-phenotype integration of molecular profiling data is a powerful and versatile tool for both biomarker discovery and for exploring the complex relationships between biological pathways and drug response.
4.Platinum anticancer drugs and photochemotherapeutic agents: recent advances and future developments.
Shaili E. Sci Prog. 2014;97(Pt 1):20-40.
Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumours. Over the last few decades, a large variety of Pt(II) and Pt(IV) complexes have been developed to improve the applicability in a wider spectrum of cancers, increase their therapeutic window and reduce the dose-limiting side effects. Photodynamic therapy (PDT), which is the administration of a photosensitiser followed by visible light activation, is a promising route to avoid damage to healthy cells and the surrounding tissue. Transition metal complexes as photochemotherapeutic agents are an attractive option for further development in the field of photoactivated chemotherapy (PACT). These complexes exhibit different numbers and types of excited states which are easily accessible upon light irradiation, subsequently giving rise to the formation of various photoproducts that can enable a distinct mode of action.