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        Promoter Methylation of CDKN2A, RARβ, and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing

        ( Jung Uee Lee ),( Hae Joung Sul ),( Ji Woong Son ) 대한결핵 및 호흡기학회 2012 Tuberculosis and Respiratory Diseases Vol.73 No.1

        Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, RARβ, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, RARβ, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16INK4A immunoexpression. Results: Hypermethylation of CDKN2A, RARβ, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16INK4A immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16INK4A immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16INK4A immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16INK4A immunoexpression loss.

      • SCOPUSKCI등재

        Promoter Methylation of CDKN2A, $RAR{\beta}$, and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing

        Lee, Jung Uee,Sul, Hae Joung,Son, Ji Woong The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.73 No.1

        Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of $p16^{INK4A}$ immunoexpression. Results: Hypermethylation of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with $p16^{INK4A}$ immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of $p16^{INK4A}$ immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed $p16^{INK4A}$ immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and $p16^{INK4A}$ immunoexpression loss.

      • KCI등재

        Negative pressure is not necessary for using fine-needle aspiration biopsy to diagnose suspected thyroid nodules: a prospective randomized study

        Jina Lee,Bong Kyun Kim,Hae Joung Sul,Jong Ok Kim,Junguee Lee,Woo Young Sun 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.5

        Purpose: Fine-needle aspiration biopsy (FNAB) can be used to diagnose thyroid cancer and other tumors. Although FNAB without negative pressure (FNAB-P) reduces the risk of blood contamination, FNAB with negative pressure (FNAB+P) increases the sensitivity of the biopsy results. Therefore, we performed a randomized study of FNAB with or without negative pressure to identify the better diagnostic method. Methods: Between March 2016 and February 2017, 172 consecutive patients were enrolled to investigate >0.5 cm nodules with indeterminate or suspicious malignant features. Patients were randomly assigned to the FNAB+P group (a 50 mL syringe was used to provide negative pressure) or to the FNAB-P group (passive collection of blood in the needle’s hub). The 2 methods’ diagnostic adequacy and quality were evaluated using an objective scoring system. The study’s protocol was registered with the World Health Organization Clinical Research Information Service (http://cris.nih.go.kr/cris, KCT0001857). Results: The patients were randomly assigned to the FNAB+P group (n = 86) or the FNAB-P group (n = 86). There were no significant intergroup differences in nodule position, size, age, consistency, calcification, BRAF mutation, or pathology. Evaluation of diagnostic adequacy parameters revealed no significant differences in background blood/clot (P = 0.728), amount of cellular material (P = 0.052), degree of cellular degeneration (P = 0.622), degree of cellular trauma (P = 0.979), or retention of appropriate architecture (P = 0.487). Furthermore, there was no significant intergroup difference in the diagnostic quality (P = 0.634). Conclusion: This prospective randomized study failed to detect significant differences in the diagnostic adequacy and quality of FNAB with or without negative pressure. Therefore, the examiner may select whichever FNAB method they prefer

      • SCOPUSKCI등재

        특수건강진단에서 발견된 고혈압 및 간질환 유소견자의 건강관리 실태에 관한 조사

        정해관,김정순,문옥륜,임현술,Cheong, Hae-Kwan,Kim, Joung-Soon,Moon, Ok-Ryun,Lim, Hyun-Sul 대한예방의학회 1992 Journal of Preventive Medicine and Public Health Vol.25 No.4

        Authors studied the workers' knowledge about the health problems detected through the previous workers' periodic health examination, content of follow-up management ana actions taken for their health problem detected on previous health examination. From June to September 1992, workers' periodic health examination was peformed on workers employed in 10 companies located in 2 middle-sized Korean cities. A questionnaire survey was done far 150 workers who reported to have $D_2$ result of either hypertension or liver disorder at the previous workers' periodic health examination done in 1991. The results are as follows; 1. Of 160 workers who had $D_2$ result of either hypertension or liver disorder in previous examination one year before, only 85 workers(51.3%, 43 workers with hypertension, 38 workers with live disorder) responded that they have such disorders. The other 65 workers responded to questionnaire were all those with C results. Respondents' knowledge about their diagnoses was relatively precise (95.2% in hypertension group, 94.6% in liver disorder group) but knowledge about classification of diseases was poor. 2. The main efforts to solve the health problem nab self management (20 spells, 55.3%), visiting clinic or hospital(6 spells, 12.8%), use of herb medicine (2 spells, 4.3%) and use of drug store(2 spells, 4.3%) in hypertension group. In liver disorder group, 30 spells (71.4%) relied on self management,6 spells (14.3%) on hospital or clinic and 9 spells (21.4%) had no effort to improve the health problem. Content of self management was low salt diet, quit smoking, regular exercise and quit alcohol drinking in order. Avoidance of salt in diet was high in hypertension group and quitting alcohol drinking was high in liver disorder group. In those with self management, 80.7% of hypertension group and 83.3% of liver disorder group continued previous effort. Those, however, who utilized clinic or hospital, only 16.7% and 50.0% were still visiting hospital or clinic. 3. Fifty seven percent of hypertension group and 64.3% of liver disorder group was presently smoking,8.5% and 11.9% reduced smoking and 21.3% and 14.3% stopped smoking. Forty nine percent of hypertension group and 28.6% of liver disorder group was presently drinking. Reduced alcohol intake was reported in 29.8% and 40.5%, 12.8ole and 23.8% stopped alcohol drinking. Sixty six percent of hypertension group and 73.8% of liver disorder group did no regular exercise, but 12.8% and 11.9% of each group increased their physical exercise far last one year. Forty three percent of hypertension group and 38.l% of liver disorder group was overweight (defined by bodymass index greater or equal than 25). Reduced body Weight was reported in 17.2% and 16.7% of each group. Reduced dietary salt intake was high in hypertension group (51.5%). The study results suggest that follow-up management after workers' periodic health examination is not satisfactory. In order to improve this situation, adequate information on the result of the workers' periodic health examination should be distributed to each worker group with health education and counselling.

      • Diagnosis and Management of Rosai-Dorfman Disease Confined to the Breast

        Bong Kyun Kim,Jina Lee,Hae Joung Sul,Woo Young Sun 조선대학교 의학연구원 2016 The Medical Journal of Chosun University Vol.41 No.3

        Rosai-Dorfman Disease is a very rare systemic immunologic disease, but most patients show improvement without specific treatment. However, when confined to the breast, it is difficult to exclude from malignancy since they are share similar radiographic characteristics. Thus, we report a case of Rosai-Dorfman Disease confined to the breast that pathological confirmation is needed to diagnose the disease via core needle biopsy or surgical excision.

      • KCI등재

        Loss of Primary Cilia Results in the Development of Cancer in the Murine Thyroid Gland

        Lee, Junguee,Yi, Shinae,Chang, Joon Young,Kim, Jung Tae,Sul, Hae Joung,Park, Ki Cheol,Zhu, Xuguang,Cheng, Sheue-yann,Kero, Jukka,Kim, Joon,Shong, Minho Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.2

        Communications at the interface between the apical membrane of follicular cells and the follicular lumen are critical for the homeostasis of thyroid gland. Primary cilia at the apical membrane of thyroid follicular cells may sense follicular luminal environment and regulate follicular homeostasis, although their role in vivo remains to be determined. Here, mice devoid of primary cilia were generated by thyroid follicular epithelial cell-specific deletion of the gene encoding intraflagellar transport protein 88 (Ift88). Thyroid follicular cellspecific Ift88-deficient mice showed normal folliculogenesis and hormonogenesis; however, those older than 7 weeks showed irregularly dilated and destroyed follicles in the thyroid gland. With increasing age, follicular cells with malignant properties showing the characteristic nuclear features of human thyroid carcinomas formed papillary and solid proliferative nodules from degenerated thyroid follicles. Furthermore, malignant tumor cells manifested as tumor emboli in thyroid vessels. These findings suggest that loss-of-function of Ift88/primary cilia results in malignant transformation from degenerated thyroid follicles.

      • KCI등재후보

        Expression of CXCR4 and SDF-1αin Primary Breast Cancers and Metastatic Lymph Nodes

        Jong-Ok Kim,Kwang-Sun Suh,Dong-Ho Lee,Hae-Joung Sul,Jung-Uee Lee,Kyu-Sang Song 한국유방암학회 2009 Journal of breast cancer Vol.12 No.4

        Purpose: A CXCR4/stroma derived factor-1α(SDF-1α, CXCL12) interaction is involved in many metastatic cancer mechanisms, including breast cancer. The primary objectives of this study were to investigate the correlation between CXCR4 and axillary lymph node metastasis and to clarify the interaction between CXCR4 in primary tumor cells and SDF-1αin metastatic lymph nodes. An analysis of the correlation between CXCR4, SDF-1αand clinicopathologic features was also performed. Methods: Representative areas from 44 invasive ductal carcinomas were selected for construction of tissue microarrays using a 5 mm punch. Breast cancers (n=44), metastatic axillary lymph nodes (n=18) and non-metastatic axillary lymph nodes (n=26) were immunohistochemically stained for CXCR4, SDF-1α, estrogen receptor (ER), progesterone receptor (PR) and HER2. The parameters of age, tumor size, nuclear grade, histologic grade, lymph node status and pathologic node (pN) stage pN0 to pN3 were evaluated. Results: CXCR4 expression was negatively correlated with increased age (p=0.005) and positively correlated with a large tumor size (p=0.043) and PR expression (p=0.027). CXCR4 expression was not correlated with metastatic lymph nodes (p=0.079) and SDF-1αexpression in metastatic lymph nodes (p=0.062). However, CXCR4 nuclear positivity is correlated with lymph node metastasis (p=0.044). SDF-1αwas not correlated with any clinicopathologic feature in a statistically significant manner. Conclusion: An evaluation of young age, large tumor size and PR expression helps predict lymph node metastasis and poor prognosis. Expression of CXCR4 nuclear positivity is correlated with a poor prognosis.

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