• Radiation Oncology Journal
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• v.7 no.2
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• pp.171-183
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• 1989

A general effect for cell proliferation has been incorporated into Roesch's survival equation (Accumulation Model). From this an isoeffect formula for the low dose-rate regimen is obtained. The prediction for total doses equivalent to 60Gy delivered at the constant dose-rate over 7 days agrees well with the dose-time data of Paterson and of Green, when the parameter ratio A/B (${\approx}{\alpha{\mu}}/2{\beta}\;where\;{\mu}$ is the repair rate) is chosen to be 0.7Gy/h. When a constant proliferation rate and known facts of division delay are assumed, an isoeffect relation between low dose-rate treatment and acute dose-rate treatment can be derived. This formula in the regimens where proliferation is negligible predicts exactly the data of Ellis that 8 fractions of 5 Gy/day for 7 days are equivalent to continuously applied 60Gy over 7days, provided the A/B ratio is 0.7 Gy/h and the $\alpha/\beta$ ratio is 4Gy. Overall agreement between the clinical data and the predictions made by the formula at the above parameter values suggests that the biologcal end points used as the tolerance level in the studies by Paterson, Green, and Ellis all agree and they are not entirely the early effects as generally assumed. The absence of dose-rate effects observed in the mouse KHT sarcoma can better be explained in terms of a large value for the A/B ratio. Similarly, the same total dose used independently of the dose-rate to treat head and neck tumors by Pierquin can be justified.

• Korean Journal of Head & Neck Oncology
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• v.26 no.2
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• pp.171-177
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• 2010

연구목적 : 비인두암 환자들을 대상으로 방사선치료 시 삼차원입체조형치료기법과 용적세기조절회전치료기법을 비교하고 이하선을 포함한 정상조직 보호에 있어 그 차이점을 알아 보고자 본 연구를 시행하였다. 대상 및 방법 : 비인두암 환자 5명을 대상으로 치료계획용 CT(computed tomography)를 시행 후 삼차원입체조형방사선치료계획 과 용적세기조절회전치료계획을 시행하였다. 이를 바탕으로 얻은 선량분포, conformity index(CI) 그리고 선량체적 히스토그램을 통해 손상위험장기(organ at risk)와 계획용표적체적(planning target volume)을 비교 분석하였다. 결 과 : 분석결과 이하선에 조사되는 평균선량이 용적세기조절회전치료계획에서는 43.9%로 삼차원입체조형치료계획에서의 89.4% 보다 유의하게(p=0.043) 감소하였다. 계획용표적체적 conformity index의 경우 용적세기조절회전치료계획 (CI=1.06)에서 삼차원입체조형치료계획(CI=2.55) 보다 유의하게(p=0.043) 향상된 결과를 보였다. 결 론 : 비인두암 환자에서 용적세기조절회전 치료계획 시 삼차원입체조형치료계획 보다 유의하게 이하선에 평균선량이 줄었고 계획용 표적체적에 대한 conformity도 유의하게 향상되는 결과를 보였다. 본 연구가 적은 수의 환자를 대상으로 하였으나 용적세기조절회전치료기법을 시행 시 구강건조증의 발생을 줄일 수 있을 것으로 기대된다. 향후 더 많은 환자군을 대상으로 한 임상연구가 필요할 것으로 사료된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.4
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• pp.391-404
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• 1991

Three anticncer agents which are different in time or dosage dependence as well as in phase specificity, namely mitomycin and adriamycin from natural products, and widely different cancer cell lines_Four epidermoid carcinomas originated from larynx, cervix, skin and gut were used toghether with one osteosarcoma as the target cell of single and combined administration of anticancer drugs. Semiautomated tetrazolium dye assay(MTT) appears to offer an attractive option for chemosensitivity of head and neck cancers since it is a simple, valid and inexpensive method of assessing chemosensitivity for large samples in a short time. The results obtained form this study were as follows. 1. Good correlations were obtained with the results of the MTT test and those of $^3H$ thymidine uptake assay. 2. $LD_{50}$ values of HIST and St.Ca. which showed relatively high doubling time on adriamycin were $30{\mu}g/ml$ and $15{\mu}g/ml$ while those of HeLa, Hep-2 and KHOS/NP were $2.1{\mu}g/ml$, $4.8{\mu}g/ml$, and $6.8{\mu}g/ml$ respectively. 3. The $LD_{50}$ value of 5-FU on five cancer cells were very high ranging from 15mg/ml to almost indefinite number, which means 5-FU is very resistant to epidermoid carcinomas or osteosarcoma examined in this study. 4. Mitomycin was relatively effective showing 80% cancer killing effect on HeLa, 70% on St. Ca. and 50% on Hep-2 at the high concentrations used. 5. Adriamycin was the most effective showing 90% cancer cell killing effect on KHOS/NP, 98% on HeLa, 80% both on Hep-2 and St. Ca. The least susceptible cancer cells toward adriamycin was HIST having only 55% cell killing effect at the high cincentration. 6. Combined therapy of adriamycin and 5-FU was more effective than single administration in all the cases examined. Most effective synergism was observed on St. Ca. at the low concentration, showing 21 times higher than each single administration.

• Radiation Oncology Journal
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• v.31 no.3
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• pp.118-124
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• 2013

Purpose: The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Materials and Methods: Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, $500mg/m^2$) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. Results: At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Conclusion: Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

• Archives of Plastic Surgery
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• v.35 no.6
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• pp.698-702
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• 2008

Purpose: Basal cell carcinoma is one of the most common cancers in the western population and the annual incidence rate is still on an increasing course. In Asian countries such as Korea, the incidence of basal cell carcinoma is reported to be remarkably low but is estimated to be in a steep increase nowadays. This study was to analyze the recent clinical trends of basal cell carcinoma in Korea by reviewing a single institution's experience. Methods: Throughout an 11-year period, the surgical excision of 143 cases of basal cell carcinoma was performed in our department. General data of these cases such as the primary site of cancer, age and sex of the patient, operative methods, recurrence rate were reviewed retrospectively. Results: Among the 143 patients included in this study, 82 patients were men and 61 patients were women. The ages ranged from 27 to 89 years with a mean age of 64.0 years. The head and neck region was the most frequently involved primary site for the cancer as 95.1% of the total cases occurred in this area. Especially the nose and perinasal area were the most frequent region, which was followed by the periorbital area, cheek, and perioral area. During this study period, 9 cases showed recurrence of the cancer as the overall recurrence rate was 6.3%. Conclusion: Gradual increase in the incidence of basal cell carcinoma was demonstrated in this study. Basal cell carcinoma showed high incidence in the old-age population as 68.5% of the total patients were more than 60 years of age. High recurrence rate was noted in the nasal region especially after local flap reconstruction. A more cautious approach is to be required when handing such high risk lesions. Multiple factors such as extended life span, increased outdoor leisure activity and exposure to sunlight, higher accessibility to medical services and increased understanding of the public about skin cancer are assumed to be the main reasons for this increase of basal cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10985-10989
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• 2015

Background: The capability for DNA double-strand breaks (DSBs) repair is crucial for inherent radiosensitivity of tumor and normal cells. We have investigated the clinicopathologic significance of DNA repair gene expression in nasopharyngeal (NP) carcinoma. Materials and Methods: A total of 65 NP cancer patients who received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs, MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues. Results: The patients comprised 42 males and 23 females, with a median age of 56 years (range, 18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and 18.5%. LIG4 (${\pm}$) were 43.1% and 56.9% respectively. The 5-year OS rate of patients with LIG4 (${\pm}$) were 90% and 67.9%, respectively (p=0.035). The 5-year TTP rate of patients with LIG4 (${\pm}$) were 75.9%, 55.5%, respectively (P=0.039). Conclusions: Our results suggest the possibility of predicting the radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4.

• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.184-191
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• 2002

연구방법 : 근치적 목적의 동시항암방사선치료를 시행받은 비인강암 환자들을 대상으로하여 치료 효과와 독성에 대한 후향적 분석을 시행하였다. 환자 및 방법 : 1993년 8월부터 1999년 3월까지 원격전이가 없는 50명의 비인강암 환자들이 방사선 치료기간 중 주 1회의 시스플라틴 $20mg/m^2$을 투여받았고, 1999년 4월부터 2000년 4월까지 20명의 환자가 상기 용량의 시스플라틴에 더하여 경구용 UFT300mg을 추가적으로 투여받았다. 총 70명 환자들의 임상기록과 병리 기록지를 검토하였다. 결 과: 연령의 중앙값은 47세 (범위 $18{\sim}76$)였고, 남자와 여자가 각각 53명과 17명 이었으며, 병기 II, III, IVA, IVB가 각각 23명, 14명, 15명, 18명이었다. 치료에 대한 반응율은 92.8%(95% C.I. $42{\sim}143%$)였고(완전반응 57명, 부분반응 8명), 총 34개월의 추적 관찰 기간 동안에 완전반응을 보인 57명 중 21명에서 재발(국소재발 5, 원격전이 11, 복합전이 5)을 하였다. 3년 무진행 생존율은 51.5%였으며 5년 생존율은 60.3%였다. 경구용 UFT의 추가적 사용은 주 1회 시스플라틴 항암치료에 비하여 반응율과 생존율 및 독성에 유의한 영향을 미치지 않았다. 결 론: 주 1회 저용량 시스플라틴$\pm$경구용 UFT를 이용한 동시항암방사선요법은 비인강암 환자의 치료에 있어서 비교적 적은 독성으로 높은 반응율을 나타내었으나, 향후 재발율을 감소시키기 위한 연구가 지속되어야 할 것으로 사료된다.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4049-4057
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• 2016

Background: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. Objective: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Materials and Methods: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. Results: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (p<0.05, OR 20, 95% CI 1.9-211.8; p<0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. Conclusions: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.24 no.1
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• pp.41-46
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• 2013

Background & Objectives : The Speech Handicap Index (SHI) is used to assess speech problem of head and neck cancer patients. The aim of this preliminary study was to evaluate the reliability and validity the Korean version SHI. Materials and Methods : Sixteen patients with oral cavity cancer and 26 normal control were participated in the study. Test-retest reliability of the Korean version of SHI was completed by 20 out of 42 subjects after 2weeks. Mann-Whitney U test was used to compare the Korean version of SHI scores between normal population and patients group. The relationship between the Korean version of SHI and diadochokinesis (DDK) was investigated using Spearman correlation coefficients. Results : The Korean version of SHI provided a high internal consistency (${\alpha}$=0.99) and test-retest reliability (Spearman rho 0.98). The mean SHI scores [total (T), speech (S), and psychosocial (P)] in normal population were 0.8 (T), 0.2 (S) and 0.4 (P), whereas those in patients group were 58.1 (T), 27.9 (S) and 27.0 (P) respectively. There were significant differences in total SHI score as well as in all of the sub-SHI scores between two groups. Moreover, significant correlation between the Korean version of SHI parameters (T, S, P) and sequential motion rate (SMR) were yielded in patients group. Conclusion : The Korean version of SHIwas reliable and valid. It can be useful as a supplementary clinical tool for diagnosing and measuring treatment efficacy of speech problems related to oral cavity cancer.