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Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade - A preliminary report
Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade - A preliminary report 5th International Conference on Head and Neck Cancer of the International-Society-of-Head-Neck-Cancer Myers, J. N., Holsinger, F. C., Bekele, B. N., Li, E., Jasser, S. A., Killion, J. J., FIDLER, I. J. AMER MEDICAL ASSOC. 2002: 875–79Abstract
Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986.Basic science, laboratory investigation.For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R-specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 micro g/mL). By means of a tetrazolium-based viable cell assay, PKI166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18 micro M (R = 0.98) for Tu159 cells and 0.23 micro M (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 x 10(6) Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion.Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model.
View details for Web of Science ID 000177346300001
View details for PubMedID 12162763