Platinum CI

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

Clinically Used Anticancer Agents. Cis-platinum Compounds 812... 

Anin, M.F., Gaucheron, F., and Leng, M. (1992) Lability of mono functional cis platinum adducts Role of DNA double helix. Nucleic Acids Res. 20, 4825-4830. 

Yaneva J, Leuba SH, van Holde K, Zlatanova J (1997) The major chromatin protein histone HI binds preferentially to cis-platinum-damaged DNA. Proc Natl Acad Sci USA 94(25) 13448-13451... 

Zimbrick JD, Aruni S, Richmond RC. Studies on radiosensitization of Escherichia coli cells by cis-platinum complexes. Int J Radiat Oncol Biol Phys 1979 5 1351-1354. 

Haselow RE, Adams GS, Oken MM, Goudsmit A, Lemer HJ, Marsh JC. Simultaneous cis-platinum (DDP) and radiation therapy (RT) for locally advanced unressectable head and neck cancer. Int J Radiat Oncol Biol Phys 1982 8 201. 

Stratford IJ, Williamson C, Adams GE. Combination studies with misonidazole and a cis-platinum complex cytotoxicity and radiosensitization in vitro. BrJ Cancer 1980 41 517-522. 

Lehane DE, Bryan RN, Horowitz B, et al. Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors. Cancer Drug Deliv 1983 l(l) 69-77. 

Haselow RE, Warshaw MC, Oken MM, et al. Radiation alone versus radiation with weekly low dose cis-platinum in unresectable cancer of the head and neck. In (Fee WE Jr. GH, Johns ME, eds). Head and Neck Cancer. Vol. 2. Philadelphia BC Decker, 1990 279-281. 

Ensley JF, Jacobs JR, Weaver A, et al. Correlation between response to cis-platinum combination and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer 1984 54 811-814. 

Nag S, Blatnik A, Soloway M. Enhancement of high intensity iodine-125 brachytherapy by cis-platinum in a murine bladder tumor model. J Urol 1984 131 1225-1228. 

Thigpen T, Shingleton H, Homesley H, et al. Cis-platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix. Cancer 1981 48 899-903. 

Wong L, Choo Y, Choy D, et al. Long-term follow-up of potentiation of radiotherapy by cis-platinum in advanced cervical cancer. Gynecol Oncol 1989 35 159-163. 

Granowetter, L., Rosenstock, J.G., Packer, R.J. (1992). Enhanced cis-platinum neurotoxicity in pediatric patients with hrain tumors. J. Neurooncol 1983 1 293-297. 

Binding sites for the platinum complexes in the DNA molecule are believed to be the amino groups of adenosines and cytidines, with the formation of a bidentate chelate ring by the cis platinum complexes159. ... 

I would argue that in innovation and in the drive to move academic technologies to industry, the second- and third-tier universities are inherently more aggressive or at least would like to be more aggressive than the first-tier universities in this. Frankly, all of our administrators hope that there is a Gatorade or a cis-platinum in their future. Among the distribution sites I would hope we would consider for the ultimate output of this conference are the second- and third-tier academia. I don t think MIT and Harvard University need to know what we have said here. If they did know it, they wouldn t change their policies anyway. 

The management of cancer includes treatment with alkylating agents (nitrogen mustards and alkyl sulfonates), antimetabolites (methotrexate and purine analogs), natural products (vinca alkaloids and antibiotics), miscellaneous compounds (hydroxyurea, procarbazine, and cis-platinum), hormones (estrogens and corticosteroids), and radioactive isotopes (see Chapter 62). 

Platinol, Platinex, Neoplatin, CACP, CPDC, DDP, c/ s-DDP, Cisplatyl, NSC-119875, cis-platinum II. 

Exposure to chromium(VI) can result in DNA-protein complexes, the identification of which may be useful as biomarkers of exposure to chromates (Costa 1991). Gel electrophoresis and immunochemical techniques were used to identify actin as the protein in a DNA-protein complex induced by potassium chromate in cultured Chinese hamster ovary cells. While the DNA-protein complexes induced by formaldehyde and ultraviolet light were different from those induced by chromate, actin was also identified as the protein in the complex induced by cis-platinum, indicating that the DNA-actin complex is not specific for chromium. However, an experiment in a group of four volunteers did not demonstrate an increase in DNA-protein crosslinks in leukocytes over a 240 minute period following the ingestion of 5 mg chromium(VI) as potassium dichromate in a 10 mg chromium/L solution or the same amount added to 300 mL of orange juice (presumably reducing chromium(VI) to chromium(III)) and diluted to 500 mL with deionized water (Kuykendall et al. 1996). Chromium levels in red cells, plasma and urine were increased. In a separate experiment in this study, a threshold dose of 52 pg chromium(VI)/L was determined for crosslink formation in cultured lymphoma cells. 

Hayes DM, Cvitkovic E, Golbey RB, et al. High dose cis-platinum diammine... 

The interaction of anticarcinogenic substances, such as cis-platinum, with nucleic acid constituents was studied by Raman spectroscopy (Bertoluzza et al., 1988). 

SYNS NSC-271675 PLATINUM(II), BIS(METHYL SELENIDE)DICHLORO-, cis- PLATINUM, DICHLORO-BIS(METHYL SELENIDE)-, cis- PLATINUM, DICHLOROBIS(SELENOBIS(METHANE))-(SP-4-2)... 

PLATINUM (II), BIS(METHYL SELENIDE)SULFATO-, HYDRATE see SNSlOO PLATINUM BLACK see PJD500 PLATINUM CHLORIDE see PJEOOO PLATINUM(I 0 CHLORIDE see PJE250 PLATINUM COMPOUNDS see PJE500 cis-PLATINUM(II) DIAMMINEDICHLORIDE see PJDOOO... 

Petitjean A, Barton JK. Tuning the DNA reactivity of cis-platinum conjugation to a mismatch-specific metallointercalator. J. Am. Chem. Soc. 2004 126 14728-14729. 

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