Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment

Wang, Y. H.; Herman, Terence S.; Teicher, Beverly A.

doi:10.1038/bjc.1987.47

Cited by 7 publications

(1 citation statement)

References 19 publications

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“…In an effort to develop effective multiple drug regimens for the treatment of cancer, Teicher and co-workers reported that [Pt(terpy)Cl] + displays a moderate degree of inhibition of the recovery of human squamous head and neck carcinoma cells following treatment with the anti-cancer drug bleomycin [70].…”

Section: Biological Activitymentioning

confidence: 99%

Platinum complexes of terpyridine: Interaction and reactivity with biomolecules

Cummings

2009

Coordination Chemistry Reviews

122

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Section: Biological Activitymentioning

confidence: 99%

Platinum complexes of terpyridine: Interaction and reactivity with biomolecules

Cummings

2009

Coordination Chemistry Reviews

122

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Cisplatin ototoxicity in children: A practical grading system

Brock¹,

Bellman²,

Yeomans³

et al. 1991

Med. Pediatr. Oncol.

260

213

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A long-term follow-up study was carried out to assess ototoxicity in children who had been treated for a malignant tumour with "standard dose" cisplatin (60-100 mg/m2 per course), and were at least 2 years from stopping treatment. The median age at diagnosis was 2 years 2 months (range 1 month to 13.5 years). On the basis of hearing assessment by pure-tone audiometry, a practical grading system of hearing loss from 0 to 4 is proposed. Moderate to severe high-frequency hearing loss (grade 2-4) was found in half the children and 10 require appropriate hearing aids. The risk of developing ototoxicity increased significantly with the cumulative cisplatin dose (P = 0.027), although there was considerable individual susceptibility. Serial follow-up testing, to a median of 4 years after completion of cisplatin treatment, showed no recovery of hearing in any of these children. We suggest careful monitoring of young children by a consultant audiological physician throughout treatment with cisplatin, particularly when doses of 400 mg/m2 and over have been reached. Alternative chemotherapy should be discussed if grade 2 ototoxicity develops.

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Interaction of platinum complexes of thiazin and xanthene dyes with hyperthermia

Herman

Teicher

Pfeffer

et al. 1990

Cancer Chemother Pharmacol

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In an attempt to develop platinum-containing drugs for use with hyperthermia that would be relatively nontoxic at 37 degrees C but would become very cytotoxic at 42 degrees or 43 degrees C, several nuclear dyes were complexed to the tetrachloroplatinum(II) dianion (PtCl4) at a ratio of 2:1. The cytotoxicity of PtCl4 complexes of three thiazin dyes (thionin, azure B, and methylene blue), the xanthene dye pyronin Y, and the thiazole dye thioflavin was examined in exponentially growing euoxic and hypoxic EMT6 cells in vitro at 37 degrees, 42 degrees, and 43 degrees C and at pH 7.40 and 6.45. Of the thiazin dye complexes, the cytotoxicity of Pt(methylene blue)2 was most enhanced at hyperthermic temperatures. Both Pt(pyronin Y)2 and Pt(thioflavin)2 also became markedly more cytotoxic at 42 degrees and 43 degrees C at pH 6.45 vs pH 7.40. In vivo tumor excision assays in the FSaIIC fibrosarcoma showed that with each of the thiazin dye-platinum complexes, hyperthermia enhanced cell kill [most effectively on Pt(methylene blue)2] but was not dose-modifying. For both Pt(pyronin Y)2 and Pt(thioflavin)2, however, administration of 43 degrees C, 30-min hyperthermia to the tumor immediately after i.p. drug injection was dose-modifying. Tumor growth delay studies in the FSaIIC tumor system demonstrated that, as with the in vitro studies, Pt(pyronin Y)2 and Pt(methylene blue)2 were most enhanced by hyperthermia [tumor growth delay increased by 4.8- and 3.0-fold, respectively, vs only 1.3-fold for cisplatin (CDDP)]. Examination of intracellular platinum levels after exposure of EMT6 cells to 25 microM of drug for 1 h at 37 degrees and 42 degrees C and at pH 7.40 and 6.45 showed that each platinum-dye complex achieved platinum levels that were 100-600 times higher at 37 degrees C and pH 7.40 than those obtained using CDDP. The platinum levels for each drug dropped markedly when exposure took place at pH 6.45. Exposure at 42 degrees C only moderately increased platinum levels in cells exposed to these drugs. Thus, for several of these drugs the level of cytotoxicity observed was in great part independent of the intracellular platinum levels achieved. Pt(pyronin Y)2 is an effective drug for use with hyperthermia, and further studies using this combination with and without radiation are under way.

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Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment

Cited by 7 publications

References 19 publications

Platinum complexes of terpyridine: Interaction and reactivity with biomolecules

Platinum complexes of terpyridine: Interaction and reactivity with biomolecules

Cisplatin ototoxicity in children: A practical grading system

Interaction of platinum complexes of thiazin and xanthene dyes with hyperthermia

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