Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

An Src-protein tyrosine kinase inhibitor to reduce cisplatin ototoxicity while preserving its antitumor effect.

Authors
Bielefeld-EC; Tanaka-C; Chen-G-D; Coling-D; Li-M; Henderson-D; Fetoni-AR
Source
AntiCancer Drugs 2013 Jan; 24(1):43-51
NIOSHTIC No.
20042587
Abstract
Ototoxicity remains a major dose-limiting side effect of cisplatin. The current studies were carried out to evaluate the effectiveness of a novel Src-protein tyrosine kinase inhibitor in protecting the ear from cisplatin ototoxicity without compromising cisplatin's antitumor effects. The Src inhibitor has been shown to be effective in protecting the ear from noise-induced hearing loss. Three studies were carried out to determine whether this compound has otoprotective activity in rats treated with cisplatin. The first two studies used the Src inhibitor as a cotreatment with single doses of cisplatin in Fischer 344/NHsd rats and nude rats, respectively. Cochlear damage was assessed by auditory brainstem response threshold shifts and outer hair cell loss. The third study was carried out in nude rats with implanted HT-29 tumors, and the Src inhibitor was administered as a cotreatment with a lower dose of cisplatin. Cochlear damage and changes in tumor volume were assessed in the third study. In the first two studies, cotreatment with the Src inhibitor reduced cisplatin-induced hearing loss significantly. In the third study, little hearing loss was induced because of the use of a lower dose of cisplatin. However, cotreatment with the Src inhibitor did not exert a negative effect on cisplatin's slowing of tumor growth in the treated rats. The findings suggest that the Src inhibitor may provide an effective cotreatment with cisplatin to reduce cisplatin's ototoxicity, without compromising its antitumor capability
Keywords
Animals; Animal-studies; Auditory-system; Exposure-levels; Exposure-limits; Hearing-disorders; Hearing-impairment; Hearing-loss; Laboratory-animals; Laboratory-testing; Noise-exposure; Noise-levels; Noise-measurement; Pharmacology; Ototoxicity; Proteins; Antitumor-agents; Protective-materials; Dose-response; Drug-interaction; Drug-therapy; Adenocarcinomas; Antineoplastic-agents; Ear-protection; Cell-damage; Inner-ear; Author Keywords: apoptosis; cisplatin; cochlea; outer hair cell; Src
Contact
Eric C Bielefeld, Department of Speech and Hearing Science, The Ohio State University, 110 Pressey Hall, 1070 Carmack Road, Columbus, OH 43220, USA
CODEN
ANTDEV
CAS No.
15663-27-1; 55520-40-6
Publication Date
20130101
Document Type
Journal Article
Email Address
bielefeld.6@osu.edu
Funding Type
Grant
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008113; B20130531
Issue of Publication
1
ISSN
0959-4973
Source Name
Anti-Cancer Drugs
State
OH; OR; NY
Performing Organization
State University of New York at Buffalo
TOP