Central mucoepidermoid carcinoma of the mandible: tumorigenesis within a keratocyst.
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Biomedical subjects
Publications and source records attributed to F Christopher Holsinger.
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BACKGROUND: 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. STUDY DESIGN: Basic science, laboratory investigation. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: Despite advances in our understanding, prevention, and treatment of head and neck squamous cell carcinoma (SCC), the 5-year survival rates for patients remain low. This poor prognosis for head and neck SCC and SCC of the oral tongue (SCCOT) in particular reflects a limited understanding of the mechanisms of local and regional metastasis, which accounts for a majority of deaths. To analyze the molecular and cellular mechanisms of metastasis, we have developed an orthotopic nude mouse model of SCCOT. EXPERIMENTAL DESIGN: Nude mice were injected submucosally in the tongue or subcutis with human squamous cell carcinoma of the oral cavity cell lines Tu159, Tu167, and MDA1986. The mice were necropsied and examined for the presence of primary tumors, and regional and systemic metastases. RESULTS: For all three of the squamous cell carcinoma of the oral cavity cell lines, tumors developed more readily in the orthotopic site, the tongue, than in the ectopic subcutis. MDA1986 cells were highly tumorigenic, particularly at the orthotopic site, with as few as 5 x 10(3) cells producing tumors in all of the mice. In contrast, s.c. tumor formation required at least 1 x 10(5) cells. The tumorigenicity observed between those mice given submucosal inoculation and those mice given s.c. inoculation (P < 0.0001). Regional metastases initially occurred in <10% of mice. To generate tumor lines of increased metastatic potential, regional metastases were isolated from cervical lymph nodes after the development of orthotopic tongue tumors. Serial passage of these lymph nodes resulted in a cell line more metastatic than its parental line. When injected into the tongues of mice, these cells metastasized to regional lymph nodes in 30% of mice and to the lungs in 20%. CONCLUSIONS: In this orthotopic murine model, oral tongue cancer recapitulates the behavior of human SCCOT, allowing for detailed studies of its biology and therapy.
PURPOSE: To evaluate the rate of occult metastases detected with elective neck dissection during salvage laryngectomy for radiation failures. METHODS AND MATERIALS: Retrospective review of 63 patients failing radiation therapy treated with salvage surgery between 1970 and 1999. Charts were reviewed for tumor stage, neck treatment, complications, surgical time, and survival. Median follow-up for patients with glottic and supraglottic cancers was 7.8 and 4.5 years, respectively. RESULTS: Thirty-one of 41 glottic cancer patients received elective neck dissections. Three (10%) of 31 had occult metastases. Recurrent staged rT3 and greater tumors showed a 20% rate of occult metastases. No survival advantage was noted between patients treated with elective neck dissection and those followed expectantly (P = .87). Cartilage invasion and perineural invasion in the larynx were associated with a higher risk of occult metastases (P < .05). Ten of 22 supraglottic cancer patients received elective neck dissections. Two (20%) of 10 had occult metastases, and a statistically significant survival advantage was not noted (P = .49). CONCLUSIONS: We recommend bilateral neck dissection at the time of laryngectomy for recurrent staged rT3/4 tumors and all patients with recurrent supraglottic cancers because of the higher rate of occult metastases.
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