• Journal of Preventive Medicine and Public Health
• /
• v.27 no.2 s.46
• /
• pp.217-225
• /
• 1994

The relationship between past liver disease history and the risk of primary liver cancer was analyzed in a hospital-based case-control study conducted in Seoul on 165 patients with histologically or serologically confirmed hepatocellular carcinoma and individually age- and sex-matched 165 controls in hospital for ophthalmologic, otologic, or nasopharyngeal problems. Significant association were observed for liver deseases occurring 5 or more years before liver cancer diagnosis [OR,4.9;95% confidence interval (CI), $1.6{\sim}14.0$) and family history of liver disease(OR, 9.0;95% CI, $2.1{\sim}38.8$). These associations were not appreciably modified by allowance for major identified potential confounding factors. From these results, it is possible to speculate that liver cell injuries caused by various factors might be a common pathway to developing primary liver carcinoma. Considering the significant effect of family history of liver diseases on PLCA risk after adjusting past liver disease history, there might be genetic susceptibility in the carcinogenic mechanism of liver cancer. Further investigations are needed to clarify the effect of family history of liver disease on PLCA risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.4
• /
• pp.1615-1619
• /
• 2015

Background: Promoter hypermethylation mediated gene silencing of tumor suppressor genes is considered as most frequent mechanism than genetic aberrations such as mutations in the development of cancers. BRD7 is a single bromodomain containing protein that functions as a subunit of SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well know tumor suppressor protein p53 to trans-activate genes involved in cell cycle arrest. Loss of expression of BRD7 has been observed in breast cancers and nasopharyngeal carcinomas due to promoter hypermethylation. However, the genetic status of BRD7 in oral squamous cell carcinomas (OSCCs) is not known, although OSCC is one of the most common among all reported cancers in the Indian population. Hence, in the present study we investigated OSCC samples to determine the occurrence of hypermethylation in the promoter region of BRD7 and understand its prevalence. Materials and Methods: Genomic DNA extracted from biopsy tissues of twenty three oral squamous cell carcinomas were digested with methylation sensitive HpaII type2 restriction enzyme that recognizes and cuts unmethylated CCGG motifs. The digested DNA samples were amplified with primers flanking the CCGG motifs in promoter region of BRD7 gene. The PCR amplified products were analyzed by agarose gel electrophoresis along with undigested amplification control. Results: Methylation sensitive enzyme technique identified methylation of BRD7 promoter region seventeen out of twenty three (74%) well differentiated oral squamous cell carcinoma samples. Conclusions: The identification of BRD7 promoter hypermethylation in 74% of well differentiated oral squamous cell carcinomas indicates that the methylation dependent silencing of BRD7 gene is a frequent event in carcinogenesis. To the best of our knowledge, the present study is the first to report the occurrence of BRD7and its high prevalence in oral squamous cell carcinomas.

• Radiation Oncology Journal
• /
• v.28 no.4
• /
• pp.193-204
• /
• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

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

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

• IMMUNE NETWORK
• /
• v.22 no.3
• /
• pp.22.1-22.25
• /
• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• Journal of the Korean Society of Radiology
• /
• v.82 no.4
• /
• pp.903-913
• /
• 2021

Purpose To identify the imaging features indicative of sarcoid-like reactions in patients with intrathoracic lymphadenopathy after complete remission of malignancies. Materials and Methods This study enrolled five patients with histopathologically confirmed sarcoid-like reactions that developed after cancer remission. The clinical features and findings of CT and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT were assessed. Results The underlying malignancies included breast, nasopharyngeal, colon, and endometrial cancer and lymphoma. The time intervals between complete remission of malignancy and the diagnosis of sarcoid-like reaction ranged from 6 to 78 months. CT findings of sarcoid-like reaction included bilateral hilar and mediastinal lymphadenopathies (n = 5), pulmonary nodules (1-15 mm) with peribronchovascular, fissural, or subpleural distribution, and interlobular interstitial thickening in the lungs (n = 4). ¹⁸F-FDG PET/CT revealed hypermetabolic uptake in the mediastinal and hilar lymph nodes and both lungs in the absence of extrathoracic uptake (n = 3). The sarcoid-like reactions resolved in all patients after corticosteroid treatment. Conclusion In patients with complete remission of malignancies, newly developed bilateral hilar and mediastinal lymphadenopathies with or without pulmonary nodules of perilymphatic distribution, in the absence of recurrence at the primary tumor site and extrathoracic metastasis, may suggest a sarcoid-like reaction. Such cases warrant histologic evaluation of the lymph nodes to prevent unnecessary systemic chemotherapy.

• Radiation Oncology Journal
• /
• v.28 no.2
• /
• pp.57-63
• /
• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

• Radiation Oncology Journal
• /
• v.17 no.2
• /
• pp.91-99
• /
• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• Korean Journal of Head & Neck Oncology
• /
• v.16 no.1
• /
• pp.14-19
• /
• 2000

Objectives: Epstein-Barr virus(EBV) is a B-lymphotrophic virus with a tumorigenic potential. EBV infection has been recognized as the main cause of nasopharyngeal carcinoma and Burkitt's lymphoma. Bcl-2 protein expression is known to be up-regulated by the EBV-latency associated antigen latent membrane protein(LMP). The aim of this study was to determine the incidence of EBV in squamous cell carcinomas of the larynx and the relationship between the presence of EBV and bcl-2 expression. Patients and Methods: From January 1994 to December 1977, 35 patients with primary squamous cell carcinoma of the larynx were studied. EBV genome DNA was surveyed by polymerase chain reaction(PCR) assay and then compared the results of in situ hybridization(ISH) for EBER1 using digoxigenin-tailed oligonucleotide probe. The expression of bcl-2 protein was studied by immunohistochemistry(IHC) using bcl-2 monoclonal antibody. Results: By PCR, EBV genome was detected in 22 of 35(62.9%) squamous cell carcinomas of the larynx. Nineteen of 35 cases(54.3%) showed a positive nuclear staining for EBER1 in tumor cells by ISH. Three cases showed positivity in inflammatory cells by ISH and one of them showed a positive staining of both tumor cells and inflammatory cells. Eighteen of 32 specimens(62.5%) were positive for bcl-2 protein. There was no significant correlations between the presence of EBV DNA and bcl-2 expression. Conclusions: It could be concluded that high incidence of EBV in the laryngeal cancer tissue may indicate a probable role of EBV in the development of laryngeal carcinoma.