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

Details

• Personal Author:
  Bielefeld EC ; Chen G-D ; Coling D ; Fetoni AR ; Henderson D ; Li M ; Tanaka C
• Description:
  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 [Description provided by NIOSH]
• Subjects:
  Animals Antineoplastic Agents Drug Therapy Ear Hearing Loss Hearing Loss, Noise-Induced Laboratories Noise Occupational Health Protective Clothing Safety Sense Organs

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• Keywords:
  Adenocarcinomas Animal-studies Antineoplastic-agents Antitumor-agents Auditory-system Author Keywords: Apoptosis Cell-damage Cisplatin Cochlea Dose-response Drug-interaction Drug-therapy Ear-protection Exposure-levels Exposure-limits Hearing-disorders Hearing-impairment Hearing-loss Inner-ear Laboratory-animals Laboratory-testing Noise-exposure Noise-levels Noise-measurement Ototoxicity Outer Hair Cell Pharmacology Protective-materials Proteins Src

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• ISSN:
  0959-4973
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; Ohio ; Oregon ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  43-51
• Volume:
  24
• Issue:
  1
• NIOSHTIC Number:
  nn:20042587
• Citation:
  AntiCancer Drugs 2013 Jan; 24(1):43-51
• Contact Point Address:
  Eric C Bielefeld, Department of Speech and Hearing Science, The Ohio State University, 110 Pressey Hall, 1070 Carmack Road, Columbus, OH 43220, USA
• Email:
  bielefeld.6@osu.edu
• CAS Registry Number:
  Cisplatin (CAS RN 15663-27-1) ; L-Tyrosine (CAS RN 55520-40-6)
• Federal Fiscal Year:
  2013
• Performing Organization:
  State University of New York at Buffalo
• Peer Reviewed:
  True
• Start Date:
  20050501
• Source Full Name:
  Anti-Cancer Drugs
• End Date:
  20090430
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:721f6d4f4980462625d8a4f5ceafd34ced10ee6ea03d8220303ee3199c335e51207444363ad6c487b632e0004f9a91990db1fafb10c2b37c8af4cd1f8adb2f82
• Download URL:
  https://stacks.cdc.gov/view/cdc/194768/cdc_194768_DS1.pdf
• File Type:
  [PDF - 271.16 KB ]