• 대한두경부종양학회지
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• 제35권2호
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• pp.19-25
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• 2019

Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

• 대한두경부종양학회지
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• 제30권2호
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• 대한두경부종양학회지
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• 제17권1호
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• pp.59-62
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• 2001

Objectives: We report an interim result of conformal radiotherapy in a patient with early stage cancer at the base of the tongue, which developed in a previously irradiated area. Materials and Methods: A 64-year-old male patient was diagnosed with T4N0M0 supraglottic cancer. He received 72Gy of radiation therapy from 21 November 1988 to 24 February 1989. He had local failure and underwent a salvage total laryngectomy on 28 August 1989. Subsequently, he did well. In early 1999, he suffered from throat pain. He had a 2.5cm ulcerative mass at the base of his tongue, in the area that had been irradiated previously. Biopsy showed squamous cell carcinoma. After workup, he was diagnosed with base of tongue cancer with T2N0M0. Surgery was not feasible because the morbidity was not acceptable. Since it was difficult to re-irradiate the area with a curable dose using conventional 2D radiation therapy with an acceptable morbidity, we decided to try conformal radiotherapy. We used 7 static beam ports with field sizes from $7x6.4\;to\;8x8cm^2$, using 6 and 10MV photons. The fractionation regimen was 1.8Gy, 5 times per week. He received 64.8Gy in 36 fractions from 9 April 1999 to 1 June 1999. Results: In the 21 months since radiotherapy, the patient has not experienced any acute or chronic complications, such as xerostomia. He experienced relief of pain shortly after the start of radiotherapy, showed a complete response, and is still doing well. Conclusion: Conformal radiotherapy can be used to treat cancer that develops within a previously irradiated field, with curative intent.

• 대한두경부종양학회지
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• 제17권1호
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• pp.42-47
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• 2001

Purpose: To evaluate the usefulness of ultrasonogram as a preoperative diagnostic tool in thyroid nodular diseases, this study was carried out. Materials and Methods: From January 1998 to December 1999, 51 patients who underwent thyroidectomy were analyzed retrospectively. We compared the finally histopathological results to ultrasonographical findings such as internal consistency, multiplicity of nodules, nodular ehogenicity, nodular capsule or margin, calcification of nodules. Results: There were 47 females and 4 males with 25 benign tumor, 23 malignant tumor and 3 occult carcinoma in histopathological diagnosis. The solid tumors in ultrasonography carried a probability of malignancy as 66.7%(16/24 cases) whereas cystic or mixed tumors as 16.7%(1/6cases) or 23.8%(5/21cases) (p=0.006). The single nodular diseases carried a high probability of malignancy as 50%(13/26cases) whereas multiple diseases as 28.6%(6/21cases). The hypoechogenicity of thyroid nodular disease showed a probability of malignancy as 60%(9/15cases) whereas mixed-echogenicity as 36.4%(4/11cases). The nodules with poorly-defined margin in ultrasonographic findings showed higher probability of malignancy as 63.6% (7/11cases) than the nodules with well -defined margin as 26.5%(9/34 cases) (p=0.025). The nodules with calcification in ultrasonographic findings were represented to high probability of malignancy as 70.6%(12/17cases) compared to those without calcification as 29.4%(10/34cases) (p=0.005). The differency between ultrasonic and histopathological diagnosis was high in solid nodules(33%), 3-4cm sized nodules (28.6%) and mixed echogenecity(27.3%) whereas low in complex nodules with cystic and solid nature(4.8%), 2-3 cm sized nodules(8.3%) and pooly defined margin(9.1%). The accuracies of sonography in differentiating malignacy from benign thyroid nodules were 7.1% of false positivity, 39.1% of false negativity, 60.9% of sensitivity, 92.9% of specificity and 78.4% of accuracy. Conclusion: Sonographic examination was relatively excellent test as a preoperative diagnostic tool in thyroid nodular diseases when detailed checklists were applied such as internal consistency, multiplicity of nodules, nodular ehogenicity, nodular capsule or margin and calcification of nodules.

• 대한두경부종양학회지
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• 제20권2호
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• pp.135-142
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• 2004

Objectives: The purpose of this study was to evaluate for prognostic significance of VEGF expression and tumor angiogenesis in papillary carcinomas of the thyroid. Materials and Methods: The materials were 79 cases of papillary thyroid carcinomas, and age, sex, tumor size, multiplicity of tumor, capsular invasion, lymph node metastasis, recurrence, TNM stage, DeGroot stage and AMES scale were evaluated. An immunohistochemical stains for CD 34 to estimate microvessel density (MVD), and VEGF were done. MVD was defined as an average count of vessels per ${\times}400$ power field in the most vascularized area. VEGF expression was interpreted as 1+ and 2+ according to staining intensity and percentages of positive cells. Results: Mean score of MVD was $39.7{\pm}16.9.$ MVD were significantly higher in cases with capsular invasion (p=0.0001), lymph node metastasis (p=0.0001), TNM stage III (p=0.0022), DeGroot stage III (p=0.0163) and high risk group by AMES scale (p=0.0001). VEGF 2+ expression rate was significantly increased in cases with capsular invasion and lymph node metastasis (p=0.0006, p=0.0013), and in cases with TNM stage III, DeGroot stage III and high risk group by AMES scale (p=0.0236, p=0.0003, p=0.0293). In VEGF 2 + expression group, MVD was significantly higher than in VEGF 1 + group (p=0.0008), and MVD showed positive relation to VEGF 2 + expression (r=0.4616). Conclusion: VEGF expression and high MVD were significantly correlated to capsular invasion, lymph node metastasis, TNM stage III, DeGroot stage III and high risk group by AMES scale. The expression of VEGF and high MVD could be considered to be one of prognostic factor in papillary thyroid carcinomas.

• 대한두경부종양학회지
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• 제18권2호
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• pp.142-149
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• 2002

본 연구에서는 FRTL-5 갑상선세포에서 Protein phosphatase type 1(PP-1)과 type 2A(PP-2A) 효소의 억제제인 okadaic acid에 의한 apoptosis 유도 기전에 대하여 이해하고자 하였다. FRTL-5 갑상선세포에 다양한 농도($10{\sim}80nmol$)의 okadaic acid를 처리 한 후 caspase 3와 $PLC-{\gamma}1$ 분절을 확인 한 결과 40nmol 농도에서부터 caspase 3활성과 $PLC-{\gamma}1$ 분절이 나타남을 확인하였다. Okadaic acid에 의한 apoptosis 유도 기전을 조사한 결과 anti-apoptotic 기능이 있는 Bcl-2 단백질 발현은 미약하게 감소하였으나 Bcl-xL은 농도 의존적으로 급격한 감소를 보였다. Caspase 3 효소활성을 저해하는 IAP 단백질 중 cIAP2는 okadaic acid에 영향을 받지 않았으나 cIAP1과 XIAP 단백질 발현은 농도 의존적으로 감소하였다. Okadaic acid에 의한 apoptosis 유도는 caspase 3 의존적인 기전을 보였다. Caspase 3 특이억제제를 okadaic acid와 동시에 처리 시 apoptosis가 억제되었으며 $PLC-{\gamma}1$ 단백질의 절단 현상도 방지되었다. Caspase 3의 활성을 유도하는 cytochrome c의 유리는 okadaic acid처리 농도에 의존적으로 유리하였다. 결론적으로, okadaic acid에 의한 apoptosis 유도는 caspase 3 의존적이며, Bcl-2와 IAP family 단백질 감소현상에 의하여 야기되는 것으로 생각된다.

• Radiation Oncology Journal
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• 제27권2호
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• pp.55-63
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• 2009

목 적: 근치적 치료가 힘든 두경부 진행암 환자들을 대상으로 시행된 소분할 방사선조사의 치료반응 정도를 객관적으로 평가해 보고, 이런 환자들에 대한 적절한 방사선치료 방법을 알아보고자 이 연구를 진행하였다. 대상 및 방법: 두경부에서 발생한 상피세포암종으로 진단되어 1998년부터 2008년까지 원발 병변 또는 림프절 병변에 대해 3 Gy 분할선량으로 고식적 소분할 방사선치료를 받았던 환자 31명을 대상으로 후향적 분석을 하였다. 대상 환자들의 방사선치료 전 컴퓨터단층촬영 영상자료를 통해 종양의 용적을 측정하였고, 이를 방사선치료 종료 후 2~3개월째의 컴퓨터단층촬영 자료와 비교하여 치료반응을 평가하였다. 아울러 소분할 방사선치료로 인한 치료독성의 빈도와 정도를 확인하였고, 전체 생존율 및 무진행 생존율, 그리고 생존율이나 치료반응과 관련된 예후인자들 알아보고자 통계 분석 작업을 하였다. 결 과: 대상 환자들의 평균 연령은 70세였으며, 85%의 경우가 stage 4였다. 종양의 용적은 평균 128.4 cc였고, ECOG 활동점수 상 1점과 2점이 67.7%였다. 총방사선량은 24~45 Gy (중간값 36 Gy)로 2명을 제외한 대부분의 환자가 30 Gy 이상 조사받았으며, 치료기간은 10~25일이었다. 완전반응을 보인 경우가 4명(12.9%)이었고, 19명(61.3%)의 환자에서 부분반응을 보였다. 중간 생존기간은 8.9개월이었으며, 1년 무진행생존율은 12.9%였다. 치료반응 정도에 따른 생존율의 차이를 발견할 수 있었으며, 원발 부위, 병기, 종양의 용적, 방사선치료 범위, 총방사선량 등이 생존율이나 치료반응 정도와 유의한 관련이 있었다. 치료 기간 및 치료 종결 후 grade 4 이상의 치료독성은 없었다. 결 론: 소분할 방사선치료 결과 약 74%의 환자들에서 종양이 줄어드는 것을 객관적으로 확인할 수 있었다. 적절한 분할선량 및 추가 방사선치료가 필요한 환자들의 선별에 있어서는 추가적인 연구가 필요하겠다.

• 대한두경부종양학회지
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• 제27권1호
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• pp.32-37
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• 2011

서 론 : 미세갑상선유두상암종 환자에서 불필요한 예방적 중앙 림프절절제술을 피하기 위해서 림프절 전이를 수술 전에 예측하는 수단이 필요하다. 림프관 생성 및 성장의 조절에 VEGF-C/D, VEGFR-3 pathway, podoplain이 관여된다는 사실이 밝혀져 있다. 림프관 생성 및 성장과 관련된 인자인 VEGF-C/D, podoplanin에 대한 면역조직화학염색과 반정량적 분석을 통해 미세갑상선유두상암종에서 림프절전이와의 관련성을 확인하고자 하였다. 대상 및 방법 : 2006년 9월부터 2008년 6월까지 본원에서 미세갑상선유두상암종으로 진단받고 1인 술자에 의해 갑상선 전 절제술 및 예방적 중앙 림프절절제술을 받은 104명의 환자 중 중앙 림프절 전이가 있었던 환자와 없었던 환자를 각각 25명씩 무작위로 선별하여 종양부위에 면역화학염색을 실시하여 림프관생성인자의 발현 정도를 비교하였다. 결 과 : 대상군 50예 중 VEGF-C/D는 50예(100%) 모두 발현이 되었고 podoplanin은 33예(66%)에서 발현이 되었다. 그 중 VEGF-C는 10예(20%)에서 약한 양성, 37예(74%)에서 중등도 양성, 3예(6%)에서 강한 양성소견을 보였고 VEGF-D는 9예(18%)에서 약한 양성, 37예(74%)에서 중등도 양성, 4예(8%)에서 강한 양성소견을 보였다. 중앙 림프절 전이 음성 환자 군과 양성 환자 군으로 분류하였을 때 VEGF-C/D의 발현율의 차이는 p-value가 각각 0.48, 1.00으로 통계적으로 유의한 차이를 보이지 않았다. 50예 전체를 대상으로 하여 종양의 개수, 최대크기, 검출된 전체 림프절의 수, 양성 림프절의 수, 주변조직 침범여부에 따른 VEGF-C/D의 발현도 통계적으로 유의한 차이를 보이지 않았다. Podoplanin의 경우 염색 여부에 따라 양성군과 음성군으로 나누어 분석하였을 때 종양의 개수, 최대크기, 검출된 림프절의 수, 양성 림프절의 수, 주변조직 침범여부도 통계적으로 유의한 차이를 보이지 않았다. 결 론 : VEGF-C/D는 대상군 전체(100%)에서 발현이 되었고 podoplanin은 66%에서 발현이 되었다. 림프관 생성인자로 알려진 VEGF-C/D및 podoplanin이 미세갑상선유두상암종에서 많이 발현이 되는 것으로 보아 위 인자들이 림프절 전이를 일으키는 인자 중 하나로 생각된다. 하지만 미세갑상선유두상암종에서 중앙 림프절 전이를 예측할 수 있는 인자로 부적합 한 것으로 생각되며 향후 더 많은 증례를 통해 관련성 여부에 대한 연구가 필요하고 또 다른 인자의 관련성에 대해서 연구가 필요하겠다.

• 대한두경부종양학회지
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• 제23권1호
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• pp.3-8
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• 2007

연구목적：국소적 진행성 편도암환자에서 수술적치료와 비수술적치료의 결과를 비교 분석하고자 하였다. 연구방법 : 수술 후 보조방사선요법을 시행한 군과 유도화학요법 시행 유무에 상관없이 근치적 방사선 치료 또는 항암화학-방사선 동시치료를 받은 비수술군의 임상결과를 후향적으로 분석하였다. 연구결과：52.4개월의 중앙 추적기간결과, 대상환자의 중앙 연령은 53세 이었다. 대상 환자 중 병기 Ⅲ, Ⅳ기 환자는 72명(82.8%)이었고, 49명(56.3%)이 수술적 치료를, 38명(43.7%)명이 비수술적 치료를 받았다. 방사선 조사량외에 양군간의 차이는 없었다 (수술군：60.4Gy, 비수술군：70.2Gy, p=0.02). 비수술군의 전체 생존율은 81.6%이었다. 수술군의 8명(16.3%), 비수술군의 6명 (15.8%)에서 재발이 발생하였다. 흥미로운 사실은 원격재발은 2명 모두 수술군에서 발생하였다. 병기 III, IV기의 5년 무병생존율과 전체생존율은 수술군이 각각 82.1%, 86.9%이고, 비수술군이 각각 83.3%, 83.1%이었다(p=0.96, p=0.96). 결론：수술적 치료에 비해 비수술적 치료가 활동능력이 불량한 환자에게 선호되었을 가능성이 있었음에도 불구하고, 치료성적은 비슷하였다. 편도암에서 수술적 치료와 비수술적 치료의 전향적 무작위 비교연구가 필요하다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제38권
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• pp.46.1-46.7
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• 2016

Background: Osteoradionecrosis is the most dreadful complication after head and neck irradiation. Orocutaneous fistula makes patients difficult to eat food. Fibular free flap is the choice of the flap for mandibular reconstruction. Osteocutaneous flap can reconstruct both hard and soft tissues simultaneously. This study was to investigate the success rate and results of the free fibular flap for osteoradionecrosis of the mandible and which side of the flap should be harvested for better reconstruction. Methods: A total of eight consecutive patients who underwent fibula reconstruction due to jaw necrosis from March 2008 to December 2015 were included in this study. Patients were classified according to stages, primary sites, radiation dose, survival, and quality of life. Results: Five male and three female patients underwent operation. The mean age of the patients was 60.1 years old. Two male patients died of recurred disease of oral squamous cell carcinoma. The mean dose of radiation was 70.5 Gy. All fibular free flaps were survived. Five patients could eat normal diet after operation; however, three patients could eat only soft diet due to loss of teeth. Five patients reported no change of speech after operation, two reported worse speech ability, and one patient reported improved speech after operation. The ipsilateral side of the fibular flap was used when intraoral soft tissue defect with proximal side of the vascular pedicle is required. The contralateral side of the fibular flap was used when extraoral skin defect with proximal side of the vascular pedicle is required. Conclusions: Osteonecrosis of the jaw is hard to treat because of poor healing process and lack of vascularity. Free fibular flap is the choice of the surgery for jaw bone reconstruction and soft tissue fistula repair. The design and selection of the right or left fibular is dependent on the available vascular pedicle and soft tissue defect sites.