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Elderly . SIOG Newsletter 1 , 2005 . 2 Al-Sarraf , M , Fletcher , W , Oishi , N et al. 1982 Cisplatin hydration with and without mannitol diuresis in refractory disseminated

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Abstract  

The effects of cisplatin and its trans isomer transplatin on the thermal denaturation of G-actin were studied with a Micro DSC-III differential scanning calorimeter. The denaturation enthalpy of G-actin was found to be 12 J g–1, and the denaturation temperature was 328 K. The thermal denaturation curve showed that increasing cisplatin concentration decreased the enthalpy change. However, after the ratio of cisplatin to G-actin attained 8:1 (mol:mol), the denaturation enthalpy no longer decreased. Transplatin decreased the enthalpy change more rapidly. In contrast with cisplatin, the denaturation peak at 328 K disappeared, and a strong exothermic peak appeared at 341 K when the ratio of transplatin to G-actin was 8:1 (mol:mol). The enthalpy change was 75 J g–1, which is far in excess of the range of weak interactions. This strong exothermic phenomenon probably reflects the agglutination of protein. The effects of cisplatin and transplatin on the number of the free thiol groups of G-actin are discussed.

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1997 Detection of early ototoxic effect in testicular cancer patients treated with cisplatin by transiently evoked otoacoustic emission: a pilot study Oncology 54 387

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Platmum levels have been determined in 145 samples from 24 tissues and 7 types of tumours from patients, treated with cisplatin. Sampled were 27 males (average age: 36 y, range: 22–63) and 19 females (average age: 52 y, range: 17–69), with an average total intravenous dose of 820 mg and 545 mg cisplatin, respectively. Samples were obtained via biopsy and autopsy, mostly 4–15 weeks after the last cisplatin administration. The long-term clearance of platinum from the tissues analyzed could be described by a first-order process with a half-life in the range of 175–300 days. The platinum fraction involved in the longterm total body clearance is estimated to be 22–38% of the total dose administered. However, the platinum clearance from a mature teratoma appeared to be much slower as measurable levels were detected 7.6 years after administration of the drug. The highest long-term platinum accumulations were found in liver, uterus, testes, ovary, and thyroid, and the lowest in brain and blood.

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Cisplatin (CDDP) is an antineoplastic drug used in the treatment of a wide variety of tumors. This paper describes an investigation carried out on pregnant mice after intragastric or intraperitoneally treatment with CDDP from day 11 to 13 of gestation. Platinum content in different tissues, namely liver, kidney, placenta and brain, was determined at 18 day of pregnancy. Two analytical techniques were used, i.e. neutron activation analysis and atomic absorption spectroscopy. Results of both techniques are presented and discussed in terms of precision, accuracy and sensitivity. Neutron activation analysis appears to provide results better correlated with the drug treatment.

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A simple neutron activation method is described for platinum determination in urine and serum of dogs when studying the pharmacokinetics of cisplatin, an antitumour drug. The procedure is based on the nuclear reaction198Pt(n, ψ, β)199Au, a radiochemical separation of gold, and gamma-spectrometry of the radionuclide199Au. Gold is separated as metal by coprecipitation with selenium after the addition of ascorbic acid in a highly acidic medium. The interference contribution of199Au originating from stable gold is evaluated, too.

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The proposal of this work was to investigate the effect of the radioactive (NH3)2PtCl2, cis-diamminedichloroplatinum (II) or CDDP* on malignant glioma cells and verify if the low-dose continuous internal radio-chemotherapy would be able to produce additive effects. The antitumoral activity of CDDP* and the non labeled cisplatin, CDDP, were evaluated in glioblastoma. Cisplatin was cytotoxic for glioblastoma cells in a dose dependent manner. Treatment with CDDP*, (IC50 = 1.75 ± 0.07 μM), proved to be more potent than using just CDDP, (IC50 = 4.96 ± 0.40 μM). These results suggest that cisplatin is a very potent radiosensitizer evoking a supra additive effect. Internal radio-chemotherapy treatment based on CDDP* may be useful alternative to reduce the drug concentration required for effective inhibition of glioblastoma growth.

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Orvosi Hetilap
Authors: Tamás Kullmann, Tamás Pintér, Zsolt Szepesvári, Noémi Kránitz, and Stéphane Culine

Absztrakt

A szerzők 54 éves nőbeteg esetét mutatják be. Kétoldali (Bellini-) gyűjtőcsatornából kiinduló, multiplex tüdőmetasztázisokat adó vesetumor miatt jobb oldali nephrectomia történt. Az ellenoldali vesében progrediáló daganat akut komplett anuriás veseelégtelenséget okozott. Dialízist és palliatív gemcitabin (1000 mg/m2)–cisplatin (70 mg/m2) kemoterápiát kezdtek. A kezelés mellett a beteg vesefunkciója javult, a 6 ciklust kitevő kemoterápiás vonal végeztével a dialízist felfüggesztették. Fél évvel később uralhatatlan lokális és pulmonalis progresszió miatt a beteget elvesztették. A potenciálisan nephrotoxicus cisplatin kemoterápia komplex szupportív kezelés mellett a diffúzan infiltratív tumor kontrollja révén a vesefunkciót javította, és aktív háztartási munkavégzés mellett a beteg egyéves túlélését tette lehetővé. Orv. Hetil., 2016, 157(11), 436–439.

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The literature indicates that the interaction of Tb3+ with DNA modified by the antitumour drug cis-diaminedichloroplatinum(II) (CDDP) results in substantial enhancement of the fluorescence of this cation, while no enhancement is observed in the case of DNA modified by irradiation with ionizing radiation. This study investigates the effect of Tb3+ on the survival of cultured mammalian cells treated with CDDP. HeLa cells were treated with a combination of195mPt-CDDP and TbCl3, and the relationship between lethal effect and the numbers of Tb and/or Pt atoms binding to DNA, RNA and proteins was examined. The Tb content in each fraction was determined using instrumental neutron activation analysis. It was found that the cytotoxic effect of CDDP was greatly enhanced by the presence of Tb ions (D0 of CDDP fell from 8.3 μM without Tb to 3.2 μM with 0.75 mM Tb), while no such effect was found in radiation-induced cell-killing. The number of Tb atoms bound to DNA molecules in a cell was calculated to be about 4.5·107, namely 1 per 1.400 nucleotides, under that situation.

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Cantù, M. G., Buda, A., Parma, G. és mtsai: Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J

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