Polyadenosine diphosphate-ribose polymerase (PARP) inhibition as a means of protecting the inner ear from cisplatin (CDDP)-mediated ototoxicity without affecting antitumor efficacy in vitro
| Autor: | Elke Malenke, H. Loewenheim, Hans-Georg Kopp, Martin R Mueller, Frank Mayer, A. Schrattenholz |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cisplatin
Cancer Research Programmed cell death medicine.diagnostic_test business.industry Poly ADP ribose polymerase medicine.disease Flow cytometry medicine.anatomical_structure Oncology Ototoxicity Cell culture Immunology otorhinolaryngologic diseases medicine Cancer research sense organs Hair cell Cytotoxicity business neoplasms medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 28:e13501-e13501 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2010.28.15_suppl.e13501 |
| Popis: | e13501 Background: Hearing loss can be the dose limiting toxicity of CDDP. In the treatment of germ cell tumors (GCT) or adjuvant therapy of non-small cell lung cancer (NSCLC), CDDP cannot be replaced without loss of efficacy. Inhibition of PARP, an enzyme of the base excision repair pathway, is a novel anti-neoplastic principle. PARP-activation has been identified to induce cell death following inner ear trauma. We evaluated PARP-inhibition by pirenzepin as a means to protect the ear from CDDP. Methods: In an in vitro culture model, inner ears were treated continuously with 1.4 μM CDDP. Ears were obtained from heterozygous and homozygous PARP-knock out mice and wild-type controls at postnatal day 7. The number of preserved hair cell stereocilia bundles was counted by fluorescence microscopy after labeling with phalloidin. Cytotoxicity of CDDP and the effect of pirenzepin were assessed by MTS-assays and flow cytometry using the cell lines 2102EP, NT2 (both GCT) and NCI-H460 (NSCLC). Results: In wild-type ... |
| Databáze: | OpenAIRE |
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