• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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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.

• BMB Reports
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• 제51권11호
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Radiation Oncology Journal
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• 제8권2호
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• pp.177-182
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• 1990

경북대학교병원 치료방사선과에서 1984년부터 1988년까지 치료를 받은 비인강의 편평 상피 세포암과 림프 상피종 42예를 대상으로 치료 결과를 분석하였다. 치료를 거부한 13명의 중앙 생존 기간은7.8개월이었다. 원발 병소에 적어도 70 Gy이상, 그리고 경부 임파절에 60 Gy이상 투여된 환자는 29명이었고, 이들은 모두 제 3 혹은 제 4 병기에 속하였다. 20예의 편평 상피 세포암의 국소 관해율은 $75\%였고, 림프 상피종 9예는 모두 완전 관해를 보였다. 원발병소와 임파절의 재발율은 $27.6\%였으며, 원격 전이가 치료 실패의 주종을 이루어서, 림프 상피종에서는 6예의 치료 실패 중 4예, 편평 상피 세포종에서는 10예 중 4예에서 나타났다. 3년 생존율은 편평 상피 세포종에서 $40.5\%였고, 림프 상피종에서는 $25.9\%였다. 이는 림프 상피종의 국소 관해율이 더 높았으나 원격전이가 더 빈번하고 비효율적인 화학요법의 결과라 생각된다. 경부 임파절의 위치와 생존율과의 상관 관계는 발견하지 못하였다. 이상으로 미루어, 보조적 확학 요법이 생존에 큰 이득이 없는 것으로 받아들여지고 있으나, 더 신중하고 적극적 인 화학요법이 필요할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제47권4호
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• pp.525-532
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• 1999

악성질환에서 체액성 고칼슘혈증은 주로 부갑상선호르몬관련단백질(parathyroid hormone related hormone ; PTHrP)이 매개물질로 작용하여 발생한다. 이러한 PTHrP포 인한 고칼슘혈중이 발생한 경우에는 원발성부갑상선기능항진증을 동반한 경우를 제외하고는 모든 환자에서 부갑상선호르몬(PTH) 농도는 저하되며 PTHrP는 증가하는 것으로 알려져있다. 특히 부갑상선이외의 종양에서 이소성 부갑상선호르몬을 생성한다거나 PTH와 PTHrP를 동시에 산생하는 경우는 매우 드물다. 저자들은 고칼슘혈증을 동반한 편평상피세포 폐암환자에서 혈청 부갑상선호르몬(PTH)과 부갑상선호르몬관련단백질(PTHrP)이 동시에 증가된 1례를 경험하여 이에 보고한다. 61세 남자 환자로서 혈청 칼슘은 7.5 mEq/L로 증가되어 있었으며, iPTH와 PTHrP(C 말단 부위 : 109-138)는 각각 150 pg/mL, 99.1 pmol/L로 모두 상승되어 있었다. 골전이나 부갑상선 기능 장애의 동반여부를 알기 위해서 시행한 골스캔이나 경부초음파, 전산화단층촬영, Tc-99m MIBI 스캔 검사에서 모두 정상소견을 보였다. 결론적으로, 본 증례는 고칼슘혈증을 보인 편평상피상피세포 폐암환자에서 PTH와 PTHrP가 동시에 증가된 경우이다. 이러한 매개물이 동시에 증가한 원인으로 PTH와 PTHrP을 분비하는 타병변이 있을 수 있지만, PTH와 PTHrP를 동시에 분비할 수 있는 주된 기관인 부갑상선에 대한 상기 검사상 특이한 이상소견이 없었던점으로 미루어 보아 편평상피세포 폐암조직으로부터 이소성 PTH와 PTHrP가 동시에 분비되었을 가능성도 있다.

• Radiation Oncology Journal
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• 제13권1호
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• pp.9-18
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• 1995

목적 :상악동암의 적절한 치료 방법을 알기 위하여 후향적 분석을 시행하였다. 대상 및 방법 : 1986년 1월 부터 1992년 12월 까지 전남대학교 병원에서 치료받은 상악동에서 발생한 편평상피세포암 33명을 대상으로 하였다. 남자가 24명 여자가 9명이었고 연령의 중앙간은 55세였다. 1988년에 제시된 AJCC 병기 분류법에 따른 종양의 병기는 T2 1명, T3 10명, T4 22명이었으며 경부임파절 전이는 5명에서 관찰되었다(Nl:4명, N2b;1명). 치료방법에 따라 3군으로 분류하여 분석하였으며 첫 군(FAR 군으로 명명, 16명)은 수술전 경동맥 항암화학요법(5-FU, 평균 3078mg)과 방사선치료(평균 3433cGy) 및 비타민 A(50,000 IU. daily)를 병용하고 이어서 상악전적출술 과 술 후 방사선치료(평균 2351cGy)를 시행하였다. 방사선총량은 5255cGy였다. 둘째군(SR 군으로 명명, 7명)은 상악전적출술과 술후 방사선 치료(평균 5920cGy)를 시행하였다. 셋째군(R 군으로 명명, 6명)은 근치적 목적의 방사선 치료(평균 7164cGy)만 시행하였다. 생존율 분석에는 Kaplan-Meier법을 이용하였고 두 군간의 차이에 대한 검정은 Mantel-Cox법으로 하였다. 결과 : 국소종양 제어율은 2년에 FAR, SR, R군에서 각각 $100\%$, $50\%$, $27.7\%$로 나타났다. 무병생존율은 2년에 FAR, SR, R군에서 각각 $88.9\%$, $33.3\%$, $0\%$였다. 전체적인 생존율은 2년에 FAR, SR, R군에서 각각 $88.9\%$, $40\%$, $50\%$였다. FAR군과 SR군간에, 그리고 FAR군과 R군간에 국소종양 제어율, 2년 무병생존율, 2년 생존율에 있어서의 차이는 통계학적으로 유의하였다. 그러나 SR군과 R군간의 차이는 통계학적 유의성이 없었다. 결론 :수술전 경동맥 5-FU와 비타민 A 그리고 방사선 치료를 병용 치료하여 종양의 부분적 관해를 유도한 후 상악전적출술과 추가적인 방사선 치료를 시행한 FAR군이 상악전적출술후 방사선치료를 시행한 군이나 방사선 단독치료군보다 더 좋은 성적을 보였다. 앞으로 이에 대한 전향적 연구가 필요할 것으로 사료된다.

• 대한두경부종양학회지
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• 제14권2호
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• pp.228-235
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• 1998

Objectives: Papillary microcarcinoma of the thyroid was evaluated as to the effectiveness of diagnostic modalities, lymphatic spread pattern, and therapeutic decision according to tumor size. Material and Methods: We retrospectively analyzed a clinicopathologic findings of 72 papillary microcarcinoma patients who were treated at the over 11 years between 1985 and 1995. The authors divided papillary microcarcinoma of the thyroid into two subgroups according to tumor size: $0{\leqq}5mm$ and $5<0{\leqq}10mm$. An analysis including age and gender distribution, diagnostic tools(thyroid sonogram, thyroid scan, thyroid function test, fine needle aspiration cytology, frozen section), pathological examination of lymphnode, and surgical procedures was carried out in each subgroups. Results: The carcinoma of smaller than 5mm were found in 32 patients, and of 6 -10mm were in 40 patients. The average age of patients was 45years and all of them were female. Cold nodules on thyroid scan were noticed in 53 patientss and normal findings were in 15 patients. Suspicious malignant lesions(fine calcification, solid mass, irregular margin) on thyroid sonography were detected in 23 patients and the sonography was more useful in detecting $0{\leqq}5mm$ small sized lesions than other diagnostic methods. FNAC were performed in 17 patients, and 7 patients were diagnosed as having thyroid papillary cancer. But diagnotic rate in $0{\leqq}5mm$ small sized lesions was very low(one of eights).Frozen section were performed in all patients, among these 15 patients were diagnosed as being benign diseases and false negative rates were higher in $0{\leqq}5mm$ small sized lesions than in $5<0{\leqq}10mm$ sized lesions(p-value<0.006). Only thyroidectomies were performed in 24 patients and thyroidectomy with node dissections in 48 patients. The lymphnode metastatic rates were much higher in multifocal lesions(61.5%) than in single lesion. The incidence of cervical lymphnode metastasis was 19.4% in $0{\leqq}5mm$ sized lesions and 47.9% in $5<0{\leqq}10mm$ sized lesions. Postoperative management were performed with TSH suppression therapy(T4, synthroid) in all patients and RI therapy in 29 patients. Conclusion: On the basis of our study, improved preoperative diagnostic tools for papillary microcarcinoma of the thyroid was helpful in the choice of surgical treatment. As a result of techninological progress(ultrasonography, FNAC), the pencentage of the discovery of papillary microcarcinoma has been increased. The thyroid ultrasonography was useful in detecting small sized lesions($0{\leqq}5mm$), but FNAC may not be beneficial in detecting small sized lesions($0{\leqq}5mm$). In the surgical procedure, thyroid lobectomy alone should be avoided because of the high rate of bilaterality and multifocality.

• 대한두경부종양학회지
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• 제21권1호
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• 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.