Platinum drug oxaliplatin

New Targets — is the drug active in ci latin-resistant cancers and can the drug expand the use of platinum drugs to solid tumors and other tumors historically insensitive to cisplatin intervention The rapid advance of oxaliplatin in treatanent of colon cancer is a case in point here. 

It is desirable to show how new platinum structures may differ in signalling pathways from those of cisplatin and oxaliplatin. An important example is the role of pS3, the tumor suppresor g te, in modulation of cytotoxicity of platinum drugs. BBR 3464 di lays high activity in human tumor cell lines characterized by both wild type and mutant pS3 gene (21). In contrast, on average, cells with mutant pS3 are more resistant to the effea of cisplatin (25). It has been hypothesized that sensitivity or resistance of tumor cells to cisplatin might be also associated widi the processes involving pS3 (26,27). Transfer of functional pS3 into p53-null SAOS osteosarcoma cells actually reduced cellular sensitivity... 

As a result of the toxic side effects, intense research to design new derivative Pt compounds has been developed The second-generation platinum drug carboplatin, [Pt(C6H604)(NH3)2], has less toxic side effects than cisplatin and is also more easily used in combination therapy. Its lower reactivity allows a higher dose to be administered (even up to 2000 mg/day). It appears that carboplatin is the reagent of first choice for ovarian cancer treatment, whereas oxaliplatin is known to be most effective in colon cancer treatment... 

In 1965 Rosenberg et al. (8, 9) accidentally discovered the antiproliferative effect of cis-diammine platinum complexes, which led to the first clinical trials of cis-[PtCl2(NH3)2] 1 in 1971 and resulted in the clinical use of cisplatin worldwide. Cisplatin and carboplatin 2 are the most widely used anticancer drugs, and two other analogs, nedaplatin 3 and oxaliplatin 4 (chiral centers indicated), have recently been approved for clinical use in Japan and France, respectively. 

Reconstitution of full-length BRCAl into mouse embryonic fibroblast cells with a disrupted BRCAl led to an increase in resistance to several DNA damaging agents, including the platinum compounds carboplatin and oxaliplatin, the topoisomerase 1 drugs irinotecan and topotecan, and the topoisomerase 11 drugs doxorubicin and etoposide (61). 

ICP-MS has been employed, as discussed in Section 9.5, for the determination of platinum originating from cisplatin, carboplatin and oxaliplatin in human plasma ultrafiltrate. The method developed was successfully used to support pharmacokinetic studies in cancer patients treated with cisplatin, carboplatin or oxaliplatin.5 Counterfeit products on the drug market, which have important implications for pharmaceutical companies and human health, can be clarified by mass spectrometric isotope ratio measurements. For example, precise and accurate sulfur isotope measurements (a 54S) by MC-ICP-MS, were employed to study the isotope variation of pharmaceuticals and to detect to the origin of counterfeits by Clough el al.6... 

Heavy metal compounds used to treat cancer include cisplatin, carboplatin, and oxaliplatin (see Table 36-6). These drugs, which contain platinum, are also known as platinum coordination complexes.10,27 Heavy metal drugs act like the alkylating agents that is, they form strong cross-links between and within DNA strands,... 

ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Platinum compounds-carboplatin, cisplatin, oxaliplatin... 

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