• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.105-110
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• 1987

Fourty nine patients with squamous cell carcinoma of oral tongue were reviewed retrospectively for the evaluation of clinical manifestation and for the comparison between therapeutic modalites. The gross shape of the tumor was infiltrative in 22, ulcerative in 12, ad ulcer-oinfiltrative type in 10 patients. Direct extension of the tumor was most commonly to the floor of the mouth. The incidence of nodal metastasis generally increased with tumor stage. $55\%$ of the patients showed neck nodal metastasis at the time of diagnosis. Ipsilateral subdigastric node were most commonly involved, followed by submandibular nodes. The 5-year survival rate of patients treated with surgery and radiotherapy was $58.7\%$ in contrast to $21.6\%$ in radiation alone group. Overall 5-year survival rate was $31\%$ In radiation alone group, half of the patients in stage I, II were locally controlled. But the local control In stage III, IV was much inferior to early lesions. Especially, of 4 patients combined with implantation technique, 3 were completely controlled. 5-year survival rate of these implanted patients was $50\%,\;49.4\%$ of patients treated over 7,000cGy survived 5 years. This was significant in contrast to $6.4\%$ of the group treated below 7,000cGy. The most common sites of failures were primary sites. In early lesions primary radiotherapy with implantation would be an appropriate treatment in cancer of oral tongue, operation reserved for radiation failure. Operation and adjuvant radiotherapy is recommended in cases of advanced disease.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.3
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• pp.143-154
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• 2013

Purpose: This study was to find efficacy of integrin alpha2 (${\alpha}_2$) and epidermal growth factor receptor (EGFR) as tumor marker of oral squamous cell carcinoma (SCC) and clarify the selective cell death effect of anti-integrin ${\alpha}_2$ and anti-EGFR on SCC cells, additionally testify conjugated gold nanoparticles (GNP) with air plasma for selective cell death of oral SCC. Methods: Expression of integrin ${\alpha}_2$, EGFR on human SCC cells (SCC25) were examined by western blot. SCC25 cells were treated with anti-integrin ${\alpha}_2$, anti-EGFR and analysed by Hemacolor staining, immunoflorescence staining, FACS flow cytometry. Conjugated GNP with integrin ${\alpha}_2$, EGFR antibody were treated by air plasma on SCC cells. Results: Integrin ${\alpha}_2$ and EGFR were over-expressed on SCC25 cells than normal lung WI-38 cells. The cell viability rate of SCC25 cells treated with anti-integrin ${\alpha}_2$, anti-EGFR was lower than WI-38 cells. The concentration changes of nucleus, releasing cytochrome c and apoptosis inducing factor (AIF) from mitochondria to cytosol were observed. The changes of proteins related with apoptosis were observed. Increase of bax, bcl-xL, activation of caspase-3, -7, -9, and fragmentation of PARP, DFF45 and decrease of lamin A/C in SCC25 cells were observed. In FACS, increase of sub-$G_1$ and S phase was observed. Cell cycle related proteins, Such as cyclin D1, cyclin dependent kinase (CDK) 4, cyclin A, cyclin E, CDK 2, p27 were decreased. After SCC25 cells treated with conjugatged GNP-Integrin ${\alpha}_2$, GNP-EGFR, additionally air plasma, the cell death rate was significantly increased. Conclusion: Integrin ${\alpha}_2$, EGFR were over-expressed in oral SCC cells. Anti-integrin ${\alpha}_2$, anti-EGFR in SCC25 cells induced apoptosis selectively. When GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR were treated with air plasma on SCC25 cells, cancer cells were died more selectively. GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR with air plasma could be treatment choice of oral SCC.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.6
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• pp.544-550
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• 2010

Purpose: The result of all malignant neoplasms including oral cancer is decided by long-term prognosis. However, until now, there are only a few reports about long-term prognosis of cancer secluded in the oral cavity. So, we investigated all patients that visited our clinic for oral squamous cell carcinoma (SCCa) for the last 10 years. From this survey, we hope to find important factors that influence prognosis of the disease. Patients and Methods: A retrospective study was performed for patients that visited the oral oncology clinic for oral cancers from Jan. 2001 to Feb. 2010. We selected the patients that were diagnosed with SCCa and received curative treatment. In these patients, we investigated basic epidemiology, smoking history, body mass index, recurrence rate, treatment methods, pathologic data and 5-yr survival rate. Results: There was a total of 185 patients (115 males, 70 females and mean age: 57.3 years) that visited the oral oncology clinic for oral SCCa. Areas of primary lesion were tongue (105 cases, 57%), lower gum (19 cases, 10%), floor of mouth (16 caess, 8%), retromolar trigone (12 cases, 6.5%), and buccal cheek (11 cases, 6%). Other involved areas were upper gum, palate, lip, and salivary glands-of 1 case each. The overall 5-year survival rate was 63.7%. The factors that influenced prognosis of the disease were stage of the disease, status of differentiation, recurrence, metastasis of cervical lymph node and age. Conclusion: The factors that influence prognosis of disease are stage of the disease, status of differentiation, recurrence, metastasis of cervical lymph node and age. To point out a current trend, the mean age of patients that developed oral cancer was lower than that of before. Secondly, the prevalence of oral cancer in non-smoker are on the rise. Thus, further studies on etiology and epidemiology should be done.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.6
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• pp.453-460
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• 2009

Background and Purpose: Vascular endothelial growth factor (VEGF)-C, VEGF-D and their tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. Oral mucosal squamous cell carcinoma (OMSCC) easily metastasizes to cervical lymph nodes, so we determined the expression levels of VEGF-C, VEGF-D and VEGFR-3 in oral squamous cell carcinoma. Materials and Methods: We performed Western blot analyses with 4 OMSCC cultured tumor cell lines (SCC9, KB, YD-10B, YD-38), and with 7 surgical specimens of OMSCC for the detection of VEGF-C, VEGF-D and VEGFR-3 proteins. Expression of VEGF-C mRNA as well as mRNA for VEGFR-3 in 4 OMSCC cell lines (KB, SCC-4, SCC-9, YD-10B) was investigated by RT-PCR. We also measured VEGFC/VEGF-D protein concentrations in the media and protein concentration of VEGFR-3 in cell lysates of 4 OMSCC cell lines (SCC9, KB, YD-10B, YD-38) using commerical ELISA kits. Finally, we performed immunoprecipitation for the detection of VEGF-C in cell lysates of 4 OMSCC cells (KB, SCC-4, SCC-9, YD-10B) and real-time RT-PCR for the quantification of VEGF-C mRNA. Results: In the result of Western blotting with cell lysates of 4 OMSCC cells, we could not detect the protein expression of VEGF-C, VEGF-D, and VEGFR-3. But, all tumor tissues demonstrated VEGF-C and VEGFR-3. VEGF-C mRNA was detected at various levels in 4 OMSCC cell lines. Moreover, OMSCC cells secreted VEGF-C, not VEGF-D and VEGFR-3 was also detected in cell lysates of OMSCC by ELISA. Immunoprecipitation and real-time RT-PCR revealed VEGF-C was also expressed in 4 OMSCC cell lines. Conclusion: Taken together, tumor cells of OMSCC secrete VEGF-C, not VEGF-D. And VEGFR-3 is expressed tumor cells as well as OMSCC tumor tissues, needs further study.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.105-111
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• 1997

group($22\%\;vs.\;38\%$, p=0.24). The 5YSRs of 21 patients of primary tumor extension to adjacent sites and the other 13 patients of tonsillar proper site were $28\%\;and\;38\%$, respectively but the difference was not significant statistically(p=0.52) There was a statistically significant difference in 5YSRs between the groups of the Patients who received radiotherapy in less than 61days vs more than 60days($60\%\;vs.\;18\%$, p=0.027). All living Patients without any tumor progression(n=11) had suffered from serious late sequelae such as xerostomia, edentia, dental caries and one patient had the osteoradionecrosis of mandible. On univariate analysis. the duration of radiotherapy and T-stage were the significant prognostic factors affecting 5YSR. On multivariate analysis, also the duration of radiotherapy was the only significant Prognostic factor(p=0.01). Conclusion : There was no survival difference between the radiotherapy alone and with neoadiuvant chemothe groups. Although it was a retrospective study, the role of conventional radiotherapy alone could be effective as the local treatment modality only for the early stage of tonsillar carcinomas. But for the purpose of more improved survivals and better quality of lives of living patients, other altered fractionation such as hyperfractionated radiotherapy with shorter treatment time and smaller fraction size rather than conventional radiotherapy might be beneficial and these prospective studies are needed.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.263-268
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• 1998

Many myocutaneous flaps have been used for the reconstruction of intraoral defects caused by the excision of oral cancer. Among these myocutaneous flaps, cervical island flap has been introduced by Farr et al. Although different in detail, this flap was designed as the platysma myocutaneous flap by Futrell et al in the supraclavicular site. Since many authors applied this flap to cover intraoral defect, they discussed deeply the blood supply of this flap. To improve further flap survival, it was modified by Tashiro et al. This flap makes its vascularity highly reliable. The amount of tissue needed for reconstruction can be accurately planned. The surgical and reconstruction procedure can be performed simply, rapidly, and effectively. Oral functions including deglutition, speech, and denture fitting are not compromised. With it's minimal deformity, new donor fields is not necessory. Of course, we keep in mind that this flap has limitations in patients where much bulk of tissue defects is needed and more than 3000 rad radiation due to the metastasis of neck lymph node is exposed. In three patients with intraoral squamous cell carcinoma($T_{1-3}N_0M_0$), we performed induction chemotherapy with FP regimen including pepleomycin. Thereafter, we ablated oral cancer and peformed reconstruction of intraoral defects with cervical island flap designed by Tashiro et al. Due to these significant benefits and minimal limitations, we have found that this flap is adequate for reconstruction of most intraoral defects following cancer ablation.