암의 치료 및 전이 억제를 위한 케모카인의 응용

장미라,성인옥,강광일,이혜영,백상기,김영상 충남대학교 생물공학연구소 2003 생물공학연구지 Vol.9 No.1

Chemokines take part in the migration of developmental embryonic cells, lymphocytes, eosinophils and dendritic cells. Chemokines are also related to the angiogenesis and function as a coreceptor during the infection of HIV(human immunodeficiency virus) to T lymphocytes. Recently, tumor metastasis was found to mimic the migration of lymphoid cells into inflammatory sites by chemoattraction. Several chemokines have potential therapeutic applications, mainly in cancer through their ability to attract subpopulations of lymphoid ce1ls and also through their angiostatic effects. The nature of their receptors, which are seven-transmembrane G-protein-coupled receptors, also makes them compelling candidates as therapeutic targets in many areas where chemokines are involved. Metastasis is a nonrandom process, that is, certain types of cancer preferentially metastasize to particular sites. The preferential target organs for metastasis are highly correlated with their chemokine profiles. Chemokines are eagerly waiting for therapeutic applications to selectively induce, modulate, or prevent cellular interactions in the immune response.

보조자극분자를 이용한 암치료

장미라,윤희령,성인옥,정상원,김용찬,손정희,이혜영,강광일,백상기,김영상 충남대학교 생물공학연구소 2002 생물공학연구지 Vol.8 No.1

Tumor cells express tumor-associated antigen which can be target to the cytotoxic Tlymphocytes. CTL precursor activation requires antigen recognition and cytokine help from Th cells. In this pathway, the cross-presentation mechanism, professional antigen presenting cells first pick up tumor antigen and present the antigen to Th cells. Another pathway is to activate CTL precursor by the direct priming. The tumor cells, however, lack costimulatory signal, which is required for full activation. The lymphocytes recognized specific antigen without costimulatory signal resulted in anergy. Tumor cells engineered to express the costimulatory molecules are better immunogen and induce antitumor immunity. We will discuss the recent progress in tumor therapy using the costimulatory molecules on the basis of the direct priming mechanism.

No Detection of Episomal or Integrated High-Risk Human Papillomavirus in Nonsmall Cell Lung Carcinomas among Korean Population

이정은,이용문,성인옥,강민웅,이충식,김경희 질병관리본부 2016 Osong Public Health and Research Persptectives Vol.7 No.6

Objectives: High-risk human papillomavirus (hrHPV) is known to be a representative cancer-causing agent in the genital and head and neck regions. Many studies have detected hrHPV DNA in nonsmall cell lung carcinoma. However, hrHPV-etiologic correlation in nonsmall cell lung carcinoma remains unclear. This study is designed to determine the prevalence of episomal or integrated hrHPV DNA in nonsmall cell lung carcinoma among the Korean population. Methods: Surgically resected nonsmall cell lung carcinoma tissues, including 134 cases of squamous cell carcinoma (SqCC) and 99 cases of adenocarcinoma (ADC), were examined. In situ hybridization (ISH) for detecting episomal or integrated hrHPV DNA was performed using the INFORM HPV III Family 16 Probe (B) in the Ventana-validated assay. Anyplex II HPV28 detection kit based on real-time polymerase chain reaction was used for HPV DNA detection and genotyping. Results: All members of the study population were of Korean ethnicity. Episomal or integrated hrHPV DNA ISH analysis result was negative in all 233 cases. One SqCC of 89 samples (42 SqCCs and 47 ADCs) was positive for an hrHPV genotype by Anyplex II HPV28 detection kit. Conclusion: Our finding did not demonstrate hrHPV-etiologic correlation in primary lung SqCC and ADC in the Korean population.

고유진동 해석을 통한 스트레스 리본 교량의 거동 특성

정덕희,임남형,이진옥,윤경민,성인모 한국방재학회 2014 한국방재학회 학술발표대회논문집 Vol.2014 No.-

스트레스 리본 교량(Stress Ribbon Bridge)이란 현수된 케이블에 최소 휨강성을 제공하기 위한 철근 콘크리트 상판 또는 프리스트레스트 콘크리트 상판을 케이블에 현수 형태로 설치하는 교량을 말한다. 스트레스리본 교량은 지간장에 비해 매우 얇은 두께의 상판과 최소 휨강성으로 인해 낮은 대역의 고유 주파수 성분을 가지고 있다. 이러한 낮은 고유주파수 대역으로 인해 보도 하중에 의한 공진의 위험성이 있으며, 또한 진동에 의한 케이블 수평력의 변동 등 구조적 악영향이 발생 될 수 있다. 본 연구에서는 케이블의 수평력과 새그량을 주요 변수로 하여 고유진동 해석을 수행하였으며 이를 바탕으로 스트레스 리본 교량의 거동 특성을 분석하였다.

Mutations of the BRAF Gene in Papillary Thyroid Carcinoma in a Korean Population

김경희,강동욱,김성호,성인옥,강대영 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.5

The B-type Raf kinase (BRAF) protein is a serine/threonine kinase that has an important role in cellular proliferation, differentiation, and programmed cell death. The BRAF gene has been recently found to be mutated in human carcinomas, predominantly in malignant melanoma. The aim of this study was to investigate the frequency of the BRAF mutation in papillary thyroid carcinoma (PTC) of Koreans through direct DNA sequencing of the polymerase chain reaction (PCR)- amplified exon 15 with clinicopathological features. Seventy paraffin-embedded conventional papillary carcinomas in the thyroid gland were evaluated. The BRAF missense mutation at V599E was found in 58 of 70 PTCs (83%). The frequency of our series was much higher than the frequencies of other PTC series (36-69%). The frequency of nodal metastasis was also significantly higher in the BRAF mutation group(p= 0.048). These results suggest that the BRAF mutation is involved in the carcinogenesis in most conventional PTCs, especially those occurring in Koreans, and this is a potentially valuable marker for the evaluation of prognosis of patients with PTC. These findings support the specific inhibitors of BRAF being promising targets for the disease outcome.

포스타 : 생식내분비 ; 골수 이식 후 여아의 정상적인 사춘기 발달에 영향을 주는 요인

조현희,김미란,권동진,유영옥,김장흡,김은중,이진우,김진홍,성인경 대한산부인과학회 2003 대한산부인과학회 학술대회 Vol.89 No.-

Cytopathologic features of human papillomavirus–independent, gastric-type endocervical adenocarcinoma

여민경,배고은,김동현,성인옥,서광선 대한병리학회 2022 Journal of Pathology and Translational Medicine Vol.56 No.5

Background: Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.Methods: Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.Results: Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.Conclusions: Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.

제1형 신경섬유종증과 동반된 다발성 위장관 간질종양- 2예 보고 -

김주헌,김성호,강동욱,김경희,박미자,김용일,성인옥,이성규,백행운 대한병리학회 2006 Journal of Pathology and Translational Medicine Vol.40 No.2

Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.

고속철도 교량 주거더의 솟음량에 대한 소고

이병길(Byoung-Kil Lee),강현성(Hyun-Sung Kang),성인모(In-Mo Sung),이진옥(Jin-Ok Lee),임남형(Nam-Hyung Rim) 한국철도학회 2013 한국철도학회 학술발표대회논문집 Vol.2013 No.11

철도 교량의 거더에는 시공 단계나 열차 운영단계에서 발생할 연직처짐에 대비하여 솟음(Camber)을 두며, 현재 국내 철도교량의 솟음량은 철도설계기준(노반편)에 따라 주거더의 고정하중에 의한 처짐량을 산정하여 적용하게 된다. 그러나, 주거더의 고정하중과 활하중의 1/2을 함께 고려하여 설계한 일부 고속철도 교량에서 과다한 솟음량으로 인해 궤도 PCL 층의 최소두께 확보가 곤란하였으며, 이로 인해 궤도 PCL 층의 구조적 안전성 문제를 야기하였다. 이에 따라 본 연구는 고속철도 교량 솟음 산정기준의 적정성에 대해 검토하였다. Camber is applied to girders of a railway bridge to prepare deflections by various loads on the construction or train operation. Also, camber of a railway bridge is applied to Railway Design Standard(Roadbed) to calculate the amount of dead load deflection on main girders. However, it has caused structural stability maintaining minimum thickness in track’s PCL designed excessive camber calculated the half of dead and live load in High-speed railway bridge. In this study, a suitability of camber prediction is analyzed on High-speed railway bridges.

선택적 COX-2 억제제 NS 398과 EGF 수용체 차단제 AG 1478의 복합투여가 HeLa 세포주의 방사선 감수성에 미치는 영향

윤선민(Seon Min Youn),오영기(Young Kee Oh),김주헌(Joo Heon Kim),박미자(Mi Ja Park),성인옥(In Ock Seong),강기문(Kimun Kang),채규영(Gyuyong Chai) 대한방사선종양학회 2005 Radiation Oncology Journal Vol.23 No.1

Purpose: Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods: Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy (SF2) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results: A cooperative effect were observed on the apoptosis of the HeLa cell line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of 22.70% compare with combination of the one drug with radiation, apoptosis of 8.49 %. In cell cycle analysis, accumulation of cell on G0/G1 phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity in a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and SF2 of 0.12 but the combination of one drug with radiation was not enhanced radiosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion: Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins. 목 적: 분자 표적의 선택적 억제가 방사선 세포 살상 효과를 증진시키는 것으로 알려져 있으므로 선택적 COX-2 억제제와 EGF 수용체 차단제를 HeLa 세포주에 처리한 후 방사선 효과의 상승작용을 알아보고자 하였다. 대상 및 방법: 자궁경부암 세포주인 HeLa 세포에서 EGF 수용체 차단제 AG 1478, 선택적 COX-2 억제제 NS 398과 방사선을 복합 투여하여 세포성장 억제 분석(cell growth inhibition assay)과 세포사멸 분석(apoptosis assay)을 시행하였고, 방사선 감수성 변화를 살펴보기 위해 세포생존 분석(clonogenic survival assay)을 시행하였다. 방사선 감수성 인자로는 2 Gy에서의 세포생존분획(SF2)과 linear-quadratic model을 이용한 dose enhancement ratio (DER)를 사용하였다. 방사선 감수성에 대한 작용기전 분석을 위해 flow cytometry로 세포주기 분석(cell cycle analysis)을 시행하였고, western blot 분석을 통하여 bcl-2와 bax 단백질의 발현 변화를 살펴보았다.결 과: HeLa 세포에 NS 398과 AG 1478을 방사선과 함께 복합 투여한 실험 군에서 세포사멸 정도가 가장 높게 나타났다(8.49% vs. 22.70%). 세포주기 분석 결과, 방사선과 복합 약물 처리군에서 G0/G1 세포주기 정체와 S 세포 분획 소실이 나타났으며 이러한 변화는 72시간 이후까지 지속되었다. 세포생존 분석 결과로는 방사선과 AG 1478군에서 SF2 0.68±0.07, DER 1.12를 보인 반면, 방사선과 복합약물처리군에서는 SF2 0.12±0.01, DER 3.00으로 나타났다. Western blot 분석에서는 방사선과 복합약물처리군에서 bcl-2와 bax 단백질 발현이 모두 감소하는 양상을 보였다. 결 론: 신호전달 체계를 억제하는 분자 표적 약제인 선택적 COX-2 억제제와 EGF 수용체 차단제를 방사선과 복합투여함으로써 HeLa세포의 방사선 감수성이 증가됨을 확인하였다.