ArticlePloS one2017
Pharmacogenetic variants in TPMT alter cellular responses to cisplatin in inner ear cell lines.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The genetic vulnerability to cisplatin ototoxicity: a systematic review.Scientific reports · 2019Pooled it
- Unraveling Endocannabinoid Signaling Pathways in Cisplatin-Induced Ototoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- The Role of Genetic and Non-Genetic Factors in the Occurrence of Cisplatin-Associated Ototoxicity.International journal of molecular sciences · 2025Review
- Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings.Frontiers in neurology · 2021Review
- Effects of subchronic inhalation exposure to an organophosphorus insecticide compound containing dichlorvos on wistar rats' otoacoustic emissions.Brazilian journal of otorhinolaryngologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin is a highly-effective and widely-used chemotherapeutic agent that causes ototoxicity in many patients. Pharmacogenomic studies of key genes controlling drug biotransformation identified variants in thiopurine methyltransferase (TPMT) as predictors of cisplatin-induced ototoxicity, although the mechanistic basis of this interaction has not been reported. Expression constructs of TPMT*3A, *3B and *3C variants were generated and monitored in cultured cells. Cellular TPMT*3A levels were detected at >20-fold lower amounts than the wild type confirming the unstable nature of this variant. The expression of wild type TPMT (TPMT*1) in two murine ear cell lines, HEI-OC1 and UB/OC-1, significantly mitigated their susceptibility to cisplatin toxicity. Cisplatin treatment induced Tlr4 gene expression in HEI-OC1 cells and this response was blunted by the expression of wild type TPMT but not TPMT*3A. In line with the significant mitigation of TPMT*1-expressing cells to cisplatin cytotoxicity, these findings demonstrate a drug-gene interaction between increased TPMT activity and decreased susceptibility to cisplatin-induced toxicity of inner ear cells.
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Registered trials
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