• Korean Journal of Head & Neck Oncology
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• v.13 no.2
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• pp.169-179
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• 1997

서론 : Laminin의 수용기로 알려진 Integrin $\alpha6\beta4$의 세포내 표현 정도는 편평상피암을 위시한 여러 악성종양의 전이능력 및 예후와 밀접한 상관관계가 없다고 알려져 있다. 이 Integrin은 Laminin과 같은 세포와 리간드와 결합하면 상피세포의 기저막 지주 구조물인 hemidesmosome의 세포체질 요소(cytoskeletal element)와 연관되어 그 결과 세포의 기저막과 세포내 케라틴을 연결하는 역할을 한다. Integrin $\alpha6\beta4$는 구조적으로 다른 많은 integrin들과 달리 $\beta$4의 세포질내 영역(cytoplasmic domain)이 특징적으로 크다. 이 세포질내 영역 $\beta$4 integrin의 기능은 아직 밝혀지지 않고 있으나 아마 세포 성장의 신호전달 및 악성종양의 특징인 침윤 전이에 관련할 것으로 보아지고 있다. 재료 및 방법: 저자들은 우선 $\beta$4 integrin의 wild type s-DNA와 $\beta$4 세포질내 영역(cytoplasmic domain) 및 $\beta$4의 tyrosine 인산화 반응 부위가 각각 결손된 c-DNA를 PCR을 통하여 합성하여 pRc/CMV 벡터에 삽입한 후 원래 $\beta$4 integrin의 발현이 결집된 인간 방광암 세포에 Calcium phosphate precipitation 방법으로 주입(transfection)시켜 형질변환된 세포를 면역형광법, Flow cytometry 및 Immunoprecipitation 방법으로 클로닝하여 wild type $\beta$4-full length(Clone FL), truncated $\beta$4-cytoplasmic domain(C1one CD), 및 mutated $\beta$4-tyrosine phosphorylation site (Clone M)을 얻었다. 암 세포의 부착 및 침투 능력의 기능적 연구로 모노 클로날 항체와 fibronectin, laminin, Matrigel을 단백질 기질로 사용하였으며 결과 비교를 위하여 pRc/CMV 벡터만 주입시켰던 클로운과 방광암 세포주를 $\beta$4 integrin 음성 대조군으로 또한 이 Integrin의 높은 발현을 보이는 두경부 편평상피암 세포주를 양성 대조군으로 이용하였다. 결과 : 세포부착능력에 있어서 온전한 $\beta$4 cytoplasmic domain이 존재하는 클로운이 laminin에 강한 부착능력을 보였으나 fibronectin의 부착정도는 $\beta$4 integrin의 표현정도와 관계없이 모든 클로운에서 비슷하였다. Matrigel을 투과하는 암세포 침윤 능력에서는 $\beta$4 integrin의 표현이 존재하는 클로운들이 투과 능력이 높았으나 세포외 리간드가 없는 control membrane을 사용하였을 때와 비교하여 투과능력의 차이를 보이지 않았다. 결론 : 유전자 주입(transfection) 방법으로 integrin의 다양한 클로운의 합성이 가능하여 이 Integrin의 암 세포의 부착 및 침투 능력에서의 기능을 규명 할 수 있게 한다. $\beta$4 integrin은 편평상피 암세포의 부착에 있어서 세포외 리간드 laminin과 특이 결합하여 부착 능력을 높이는 중요한 역할을 하며 편평상피 암세포의 침투에 있어서는 $\beta$4 integrin의 표현이 침투 능력을 높이는 역할을 하나 이때에는 laminin과 같은 리간드와의 특이 결합에 의존하지는 않는 것으로 사료된다.

• Journal of Oral Medicine and Pain
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• v.41 no.1
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• pp.30-33
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• 2016

Malignant tumors located in the head and neck areas intermittently show symptoms similar to a temporomandibular disorder (TMD). In our case, a patient who first visited us complaining of TMD-like symptoms, such as trismus and temporomandibular joint (TMJ) pain on the left side, was identified as a sufferer of adenoid cystic carcinoma (ACC) that arose from the left maxillary sinus. The patient may have a TMD symptom, but we are skeptical because the patient also complained of a spontaneously developed numbness on the same side of his upper lip. We observed the panoramic radiograph closely and found the blurred maxillary sinus inferior wall. Dental cone-beam computed tomography confirmed the tentative diagnosis of malignancy on the maxillary sinus. After he had been referred to the Department of Otolaryngology, the diagnosis of the ACC was confirmed. Adequate diagnosis is vital for a quick treatment of the malignancy. There are some keys for differential diagnosis of TMD-like symptoms.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6649-6655
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• 2014

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

• Korean Journal of Head & Neck Oncology
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• v.19 no.1
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• pp.34-40
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• 2003

Objective: To analyze the treatment-related parameters after the radiotherapy of T1N0 squamous cell carcinoma of the glottic larynx. Materials and Methods: Between October 1989 and August 2000, 54 patients with histologically proven T1N0 squamous cell carcinoma of the glottic larynx who received definitive radiation therapy in Department of Radiation Oncology, Asan Medical Center were analyzed. They were all males with age ranged from 31 to 80 years (median 61 years). 1997 AJCC stages were 31 T1a, 23 T1b. Patients were treated with 4-MV X-rays with a parallel-opposed two-field technique. Ten patients received 66.0-68.4Gy at 1.2Gy per fraction twice daily, 21 patients received 64.8-66.6Gy at 1.8Gy per fraction once daily, and 23 patients received 66.0Gy at 2.0Gy per fraction once daily. Follow-up period was 16-119 months (median 56 months). Results: 5-year overall survival and local control rates for patients with T1 lesions were 87.0% and 88.5%, respectively. 5-year local control with larynx preservation rate was 90.5%. Host and tumor-related prognostic factors including age, stage, anterior commissure involvement and tumor bulk proved not to be significant. Only shorter overall treatment time among treatment-related factors had correlation with imporved local control. Conclusion: Comparable high local control rate with organ preservation was achieved with primary radiation therapy and salvage surgery. Shortening of overall treatment time is related to improved local control rate. To determine the optimal fractionation scheme, randomized trial is mandatory.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.35-43
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• 1990

Retrospective analysis of survival rates was undertaken in the patients of 58 cases treated with conventional radiation therapy for malignant salivary gland tumors between January 1975 and December 1984 in Korea Cancer Center Hospital (KCCH). They were patients whose long-term follow-up was possible and who had refused surgery or had had recurrences postoperatively. Out of 58 patients, 25 patients ($43.1\%$) had mucoepidermoid carcinomas and 24 patients ($41.3\%$) adenoid cystic carcinoma. Total actuarial survival rates at 5 years and 10 years were $68.2\%\;and\;31.8\%$ respectively, but disease-free survival rates, $43.2\%\;and\;13.0\%$, respectively. According to TNM stage, the survival rates at 5 years were $86.5\%$ in $T_1,\;40.0\%\;in\;T_2+T_3,\;and\;0\%\;in\;T_4$. In terms of histologic types, 5 years disease-free survival rate of adenoid cystic carcinomas ($40.1\%$) was lower than that of mucoepidermoid carcinomas ($49.8\%$) but overall survival rate ($77.3\%$) was much higher than that of mucoepidermoid carcinomas ($51.5\%$). There-fore, we concluded that the patients, who had had disease after failure of treatment, could survive during a certain period of time and their alive times were 2 years on the average. There was a difference in survival rates in the mucoepidermoid carcinomas in terms of histological grade of differentiation and it was a arbiter in prognosis: 5 YSR of low-grade was $78.8\%$ and higher 2 times than that of high-grade. There was no difference in survival rates according to location and sex. The number of patients having minor salivary gland tumors was 6 cases and their actuarial 5 YSR was $32.3\%$. Consequently, prognostic factors which influence the survival rates of patients with malignant salivary gland tumors are thought to be 1) histological subtypes 2) T and N staging (AJCC) 3) histological grade, especially in mucoepidermoids.

• The Journal of Korean Society for Radiation Therapy
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• v.25 no.1
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• pp.1-8
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• 2013

Purpose: A selection of proper energy in treatment planning is very important because of having different dose distribution in body as photon energy. In generally, the low energy photon has been used in intensity-modulated radiation therapy (IMRT) for head and neck (H&N) cancer. The aim of this study was to evaluate the effect of partially used high energy photon at posterior oblique fields on IMRT plan for H&N cancer. Materials and Methods: The study was carried out on 10 patients (nasopharyngeal cancer 5, tonsilar cancer 5) treated with IMRT in Seoul National University Bundang Hospital. CT images were acquired 3 mm of thickness in the same condition and the treatment plan was performed by Eclipse (Ver.7.1, Varian, Palo Alto, USA). Two plans were generated under same planing objectives, dose volume constraints, and eight fields setting: (1) The low energy plan (LEP) created using 6 MV beam alone, (2) the partially used high energy plan (PHEP) created partially using 15 MV beam at two posterior oblique fields with deeper penetration depths, while 6 MV beam was used at the rest of fields. The plans for LEP and PHEP were compared in terms of coverage, conformity index (CI) and homogeneity index (HI) for planning target volume (PTV). For organs at risk (OARs), $D_{mean}$ and $D_{50%}$ were analyzed on both parotid glands and $D_{max}$, $D_{1%}$ for spinal cord were analyzed. Integral dose (ID) and total monitor unit (MU) were compared as addition parameters. For the comparing dose to normal tissue of posterior neck, the posterior-normal tissue volume (P-NTV) was set on the patients respectively. The $D_{mean}$, $V_{20Gy}$ and $V_{25Gy}$ for P-NTV were evaluated by using dose volume histogram (DVH). Results: The dose distributions were similar with regard to coverage, CI and HI for PTV between the LEP and PHEP. No evident difference was observed in the spinal cord. However, the $D_{mean}$, $D_{50%}$ for both parotid gland were slightly reduced by 0.6%, 0.7% in PHEP. The ID was reduced by 1.1% in PHEP, and total MU for PHEP was 1.8% lower than that for LEP. In the P-NTV, the $D_{mean}$, $V_{20Gy}$ and $V_{25Gy}$ of the PHEP were 1.6%, 1.8% and 2.9% lower than those of LEP. Conclusion: Dose to some OARs and a normal tissue, total monitor unit were reduced in IMRT plan with partially used high energy photon. Although these reduction are unclear how have a clinical benefit to patient, application of the partially used high energy photon could improve the overall plan quality of IMRT for head and neck cancer.

• Radiation Oncology Journal
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• v.28 no.1
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• pp.9-15
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• 2010

Purpose: This study was performed to examine the neck failure patterns after a complete response (CR) to definitive radiotherapy for advanced head and neck cancer patients, as well as evaluate the clinical significance of the results of this study. Materials and Methods: Between 1987 and 2008, the clinical data of patients who had been treated with radical radiotherapy for primary squamous cell carcinomas and enlarged cervical lymph nodes was analyzed retrospectively. Ultimately, the cases that showed CR of the cervical lymph node lesions to full-dose radiotherapy were included in this study. The recurrent rate and sites in the cervical lymphatic area were evaluated periodically by radiologic imaging studies, along with some factors which might have affected the rate of recurrence. Results: A total of 73 patients who achieved CR in neck area after radiotherapy were included in this study. The rate of subsequent neck failure among those patients was 19.2%. There was only a 5.5% failure rate in the 55 patients who underwent radiotherapy in their primary site. Eighty percent of the recurrent cases were found within 3 years (median follow-up, 68 months). The majority of neck recurrent cases (47%) were accompanied with the failure of the primary lesions. The initial response of the primary site and the method of radiotherapy simulation were significant prognostic factors associated with the nodal recurrence rate. Conclusion: The recurrence rate of cervical nodes in patients with CR to radiotherapy in the primary site and neck area was about 5%. These patients could be followed up with close observation without a planned neck dissection.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.137-142
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• 2005

Purpose: To analyze the outcome of radiation therapy for patients with a metastatic carcinoma of cervical lymph nodes from an unknown primary (MUO), and identify the prognostic factors for these patients. Materials and Methods: Between July 1981 and June 1999, 39 patients with MUO underwent radiation therapy with curative intent. Twelve patients were treated with radiation therapy alone (Group 1), 8 with neoadjuvant chemotherapy followed by radiation therapy (Group 2), and 19 with either an excision or neck dissection and postoperative radiation therapy (Group 3). There were 31 males and 8 females, with a median age of 55 years, ranging from 25 to 77 ears. The median duration of follow-up was 38 months, ranging from 3 to 249 months. Results: The 5-year overall survival rate was $55\%$. According to the treatment modality, the 5-year disease-free survival rates of Groups 1, 2 and 3 were 48, 19 and $75\%$, respectively (p=0.0324). In addition to the treatment modality, the appearance of the primary site was a significant prognostic factor for disease-free survival (p=0.0085). Conclusion: Surgical resection and radiation therapy achieves a superior disease-free survival compared to radiation therapy alone, either with or without chemotherapy Further investigation Is needed to evaluate the role of chemotherapy in the treatment of MUO.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.6
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• pp.434-439
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• 2002

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. OSCC generally has a poor prognosis due to its tendency towards a local invasion and subsequent metastasis, which is mediated by multiple proteolytic enzymes and angiogenesis. Soy products contain high levels of isoflavonoids, including the tyrosine kinase inhibitor, genistein, which has been identified as a potent inhibitor of cell proliferation and in vitro angiogenesis. The purpose of this in vitro study is to evaluate the anti-cancer effect of genistein with respect to the angiogenesis and basement membrane invasion in OSCC. The highly invasive OSCC cell line, HSC-3 cells were cultured in the presence of $10{\mu}M$ genistein for 24h. To evaluate the effects of genistein on the invasiveness and the gelatinolytic activity, in vitro invasion assay and zymography were performed. In order to evaluate the effect on the VEGF and bFGF mRNA expression, RT-PCR and northern hybridization reaction, and chemiluminescence detection were applied. The in vitro invasion assay showed that the genistein treatment reduced the cellular invasion through the artificial basement membrane and significant difference between the control group and the genistein treated group was shown in MMP-2 activity. Especially, the 62 kDa activated form of MMP-2 in the control group was 1.8 times higher than that in the genistein treated group. The results of the northern blot analyses indicated that VEGF mRNA expression in the genistein treated group was significantly down regulated. This study showed that genistein inhibits angiogenesis and reduces basement membrane invasion in OSCC. It seems to support the possibility of genistein as an anti-cancer agent.

• Radiation Oncology Journal
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• v.37 no.2
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• pp.73-81
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• 2019

Purpose: There is sparse literature on treatment outcomes research on resectable oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to measure the treatment outcomes, explore the failure patterns, and identify the potential clinicopathological prognostic factors affecting treatment outcomes for resectable OTSCC. Materials and Methods: It is a retrospective analysis of 202 patients with resectable OTSCC who underwent upfront primary surgical resection followed by adjuvant radiotherapy with or without concurrent chemotherapy if indicated. Results: The median follow-up was 35.2 months (range, 1.2 to 99.9 months). The median duration of locoregional control (LRC) was 84.9 months (95% confidence interval, 67.3-102.4). The 3- and 5-year LRC rate was 68.5% and 58.3%, respectively. Multivariate analysis showed that increasing pT stage, increasing pN stage, and the presence of extracapsular extension (ECE) were significantly associated with poorer LRC. The median duration of overall survival (OS) was not reached at the time of analysis. The 3- and 5-year OS rate was 70.5% and 66.6%, respectively. Multivariate analysis showed that increasing pT stage and the presence of ECE were significantly associated with a poorer OS. Conclusion: Locoregional failure remains the main cause of treatment failure in resectable OTSCC. There is scope to further improve prognosis considering modest LRC and OS. Pathological T-stage, N-stage, and ECE are strong prognostic factors. Further research is required to confirm whether adjuvant therapy adds to treatment outcomes in cases with lymphovascular invasion, perineural invasion, and depth of invasion, and help clinicians tailoring adjuvant therapy.