The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study

J Jason Clark; Matthew Provenzano; Henry R Diggelmann; Ningyong Xu; Skylar S Hansen; Marlan R Hansen

doi:10.1097/MAO.0b013e31817f7398

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The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study

Journal article

Peer reviewed

The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study

J Jason Clark, Matthew Provenzano, Henry R Diggelmann, Ningyong Xu, Skylar S Hansen and Marlan R Hansen

Otology & neurotology, Vol.29(6), pp.846-853

09/2008

DOI: 10.1097/MAO.0b013e31817f7398

PMCID: PMC2652856

PMID: 18636037

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Abstract

To analyze the ability of ErbB inhibitors to reduce the growth of vestibular schwannoma (VS) xenografts. Vestibular schwannoma xenografts were established in the interscapular fat pad in nude mice for 4 weeks. Initially, a small cohort of animals was treated with the ErbB2 inhibitor trastuzumab or saline for 2 weeks. Animals also received bromodeoxyuridine injections to label proliferating cells. In a longer-term experiment, animals were randomized to receive trastuzumab, erlotinib (an ErbB kinase inhibitor), or placebo for 12 weeks. Tumor growth was monitored by magnetic resonance imaging during the treatment period. Cell death was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling of fragmented DNA. Tumors can be distinguished with T2-weighted magnetic resonance imaging sequences. Trastuzumab significantly reduced the proliferation of VS cells compared with control (p < 0.01) as analyzed by bromodeoxyuridine uptake. Control tumors demonstrated slight growth during the 12-week treatment period. Both trastuzumab and erlotinib significantly reduced the growth of VS xenografts (p < 0.05). Erlotinib, but not trastuzumab, resulted in a significant increase in the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling of fragmented DNA-positive VS cells (p < 0.01). In this preliminary study, the ErbB inhibitors trastuzumab and erlotinib decreased growth of VS xenografts in nude mice, raising the possibility of using ErbB inhibitors in the management of patients with schwannomas, particularly those with neurofibromatosis Type 2.

Magnetic Resonance Imaging

Erlotinib Hydrochloride

Neuroma, Acoustic - diagnosis

Antibodies, Monoclonal - pharmacology

Genes, erbB - drug effects

Neuroma, Acoustic - surgery

Antibodies, Monoclonal - therapeutic use

Antibodies, Monoclonal, Humanized

Animals

Mice, Nude

Protein Kinase Inhibitors - therapeutic use

Quinazolines - therapeutic use

Fluorescent Antibody Technique

Cell Proliferation - drug effects

Mice

Protein Kinase Inhibitors - pharmacology

Cell Death - drug effects

Neuroma, Acoustic - drug therapy

Quinazolines - pharmacology

Trastuzumab

Details

Title: Subtitle: The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study
Creators: J Jason Clark - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242-1078, USA
Matthew Provenzano
Henry R Diggelmann
Ningyong Xu
Skylar S Hansen
Marlan R Hansen
Resource Type: Journal article
Publication Details: Otology & neurotology, Vol.29(6), pp.846-853
DOI: 10.1097/MAO.0b013e31817f7398
PMID: 18636037
PMCID: PMC2652856
NLM abbreviation: Otol Neurotol
ISSN: 1531-7129
eISSN: 1537-4505
Publisher: United States
Grant note: K08 DC006211-01A1 / NIDCD NIH HHS T32 DC000040 / NIDCD NIH HHS KO8 DC006211 / NIDCD NIH HHS K08 DC006211 / NIDCD NIH HHS
Language: English
Date published: 09/2008
Academic Unit: Molecular Physiology and Biophysics; Neurosurgery; Otolaryngology
Record Identifier: 9984006304502771

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