Disease relevance of NSC363812

• These biotransformation products could play a role in tetraplatin effectiveness and/or toxicity [1].
• Comparison of cellular accumulation and cytotoxicity of cisplatin with that of tetraplatin and amminedibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) in human ovarian carcinoma cell lines [2].
• A combination of tetraplatin and Adriamycin in mice bearing i.p. implanted L1210 leukemia produced more long-term survivors over a wider range of doses than could be achieved with either drug alone [3].
• In vivo, following p.o. administration using the cisplatin-sensitive murine ADJ/PC6 plasmacytoma, JM216 showed antitumor selectivity far superior to that observed for either cisplatin, carboplatin, or tetraplatin [4].
• Both bladder carcinoma cell lines, both melanoma cell lines, and one of the two glioblastoma cell lines were resistant to both oxaliplatin and tetraplatin [5].

High impact information on NSC363812

• In general, cross-resistance to mixed amine analogues was partial in cisplatin- and tetraplatin-resistant cells and decreased (in L1210/DDP and 2780CP) or increased (in L1210/DACH and 2780TP) with increase in the alicyclic ring size [6].
• Tetraplatin (i.p.) first caused slowing of sensory nerve conduction (-14.4% of controls; P < 0.05) at a dose (1 mg/kg) that was free of constitutional toxicity [7].
• In conclusion, p.o. bisacetatoamminedichlorocyclohexylamineplatinum(IV) shows a lack of neurotoxicity compared to parenterally administered cisplatin and tetraplatin at the maximal tolerated dose in rats [7].
• Of the cells with acquired cisplatin resistance, the HCT8/DDP cell line showed no resistance to tetrachloro(trans-DL)1,2-diaminocyclohexaneplatinum(IV) (ormaplatin, formerly known as tetraplatin), while the A2780/DDP cell line was just as resistant to ormaplatin as to cisplatin [8].
• Oxaliplatin was similar to cisplatin and tetraplatin in protein binding; 85-88% of all platinum from oxaliplatin (5, 10, or 20 micrograms/ml) was bound to plasma proteins within the first 5 h with an average half-life of 1.71 +/- 0.06 h [5].

Chemical compound and disease context of NSC363812

• Circumvention of acquired tetraplatin resistance in a human ovarian carcinoma cell line by a novel trans platinum complex, JM335 [trans ammine (cyclohexylamine) dichloro dihydroxo platinum (IV)] [9].
• Acquired resistance to tetraplatin [d,1-trans-1,2-diaminocy-clohexane tetrachloroplatinum (IV)] has been generated in vitro in the human ovarian carcinoma cell line PXN94; the derived line, PXN94tetR, was 24-fold resistant to tetraplatin [9].
• We have studied the effect of extracellular reduced glutathione (GSH) on the cytotoxicity and biochemical pharmacology of tetraplatin in L1210 leukemia cells [10].
• Compared to our data obtained previously using human ovarian carcinoma cell lines, all five lines were relatively resistant to cisplatin, carboplatin, iproplatin and tetraplatin [11].
• Reduction of tetrachloro(dl-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) toxicity by the administration of diethyldithiocarbamate (DDTC), S-2(3-aminopropylamino)ethylphosphorothioic acid (WR-2721), or sodium selenite in the Fischer 344 rat [12].

Biological context of NSC363812

• However, the biotransformations of tetraplatin have not been studied in detail [13].
• The correlation between GSH levels and IC50 values for melphalan (r = 0.76) or tetraplatin (r = 0.60) was not as significant [14].
• While HX/155cisR was cross-resistant to tetraplatin and carboplatin, novel platinum (II) and (IV) ammine/amine complexes, including JM216 and JM221, partially circumvented resistance (resistance factors of 1.5-2) [11].
• Pharmacokinetics of intravenously injected [3H]tetrachloro(D,L-trans)1,2-diaminocyclohexane platinum (IV) (tetraplatin) in mice [15].
• DACH-Pt(II)Cl2 (4.21 mg/kg, ip) gave similar plasma Pt kinetics to that seen with the combination of tetraplatin and GSH [16].

Anatomical context of NSC363812

• An unexpected biotransformation pathway for tetrachloro-(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) in the L1210 cell line [13].
• Using six pairs of acquired cisplatin-resistant and parent human tumor cell lines (four ovarian, one testicular, and one cervical) JM216 exhibited non-cross-resistance (resistance factor of < 1.5) in three whereas tetraplatin exhibited partial or full cross-resistance in all six pairs [4].
• Plasma and ascitic fluid from tumor-bearing mice demonstrated equivalent abilities to reduce tetraplatin rapidly [16].
• Only DDTC was moderately effective in preventing tetraplatin-induced decreases in platelet and lymphocyte counts [12].
• Cisplatin had little effect on the excretion rates of the brush border enzymes alkaline phosphatase and maltase, whereas tetraplatin caused an initial elevation with delayed onset of peak excretion rates at 8 days postinjection [17].

Associations of NSC363812 with other chemical compounds

• The in vitro cellular uptake of platinum by L1210 cells at 37 degrees C was about 4-fold higher after exposure to tetraplatin compared to cisplatin following a 2-h incubation at the two concentrations examined (2.5 and 5 micrograms/ml) [3].
• The marked similarity in cytotoxicity between oxaliplatin and tetraplatin may be due to the formation of (trans-1,2-diaminocyclohexane)dichloroplatinum(II) in tissue culture media [5].
• However, depletion of glutathione by buthionine 1-sulphoximine sensitizes all cell lines to the effects of cisDDP, chip and tetraplatin [d,1-trans-tetrachloro-1,2-diamino-cyclohexanplatinum (IV)] [18].
• A 158-base-pair double-stranded DNA fragment, derived from pBR322 plasmid DNA, was modified by either CDDP, tetrachloro(dl-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) or trans-DDP (the stereoisomer of CDDP and clinically ineffective) [19].
• Synthesis, physical properties, and antitumor activity of tetraplatin and related tetrachloroplatinum(IV) stereoisomers of 1,2-diaminocyclohexane [20].

Gene context of NSC363812

• Tetraplatin and lobaplatin showed, respectively, partial and complete cross-resistance in GLC4/CDDP but no cross-resistance in Tera-CP [21].
• At an optimal dose of 5.7 mg/kg/injection given as a single dose on days 1, 5, and 9, tetraplatin increased the median life span over controls by more than 566% with 5 of 8 long-term (50-day) survivors [3].
• Only one of the six parent tumour lines (PXN/100) was markedly sensitive to tetraplatin [22].
• Intracellular accumulations of tetraplatin in both L1210/0 and L1210/DDP cells were increased by GSH, whereas in L1210/DACH cells platinum uptake decreased in the presence of the thiol [10].
• Inhibition of brain choline acetyltransferase by tetraplatin [23].

Analytical, diagnostic and therapeutic context of NSC363812

• We have followed the intracellular biotransformations of tetraplatin and PtCl2(dach) in the L1210 cell line by a two-step high performance liquid chromatography separation procedure described previously (Mauldin et al., Cancer Res., 48: 5136-5144, 1988) [13].
• Ormaplatin (also known as tetraplatin) is a platinum-containing analogue which has recently undergone clinical trials [24].
• A dose of 10 mg/kg intraperitoneally of tetraplatin produced a tumour growth delay of about 4.3 days which was increased to about 6 days with the addition of local hyperthermia (43 degrees C, 30 min) to the drug treatment [25].
• Since tetraplatin, another platinum analog being evaluated in phase I clinical trials, has a favorable therapeutic profile when compared to cisplatin, we examined the comparative nephrotoxicity of tetraplatin and cisplatin in rats when both compounds were administered at equimolar doses [26].
• Results showed that relatively high GSH levels may be involved, at least partially, in determining platinum drug resistance in vivo in at least some of the tumour models studied (ADJ/PC6 carboplatin and tetraplatin resistant tumours; L1210 cisplatin and tetraplatin resistant tumours and the HX/62 and OVCAR-3 human ovarian carcinoma xenografts) [27].

References