알레르기성 기도 질환의 동물모델에서 줄기 세포 치료

조규섭 ( Kyu-sup Cho ) 대한천식알레르기학회(구 대한알레르기학회) 2016 Allergy Asthma & Respiratory Disease Vol.4 No.3

Allergic airway diseases are characterized by T-helper type 2 (Th2)-skewed eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness. The excessive activation of Th2 cells due to insufficient suppression of regulatory T cells (Tregs) is thought to play a major role in the initiation and development of allergic airway disease. Several studies have shown that stem cells provide a significant reduction in allergic airway inflammation and improve lung function in animal models. The immunomodulatory effects of stem cells in allergic airway disease may be mediated by the up-regulation of Tregs and increases in several soluble factors, such as prostaglandin E2, transforming growth factor-β, interleukin-10, and indoleamine 2, 3-dioxygenase. This review examines the current understanding of the immunomodulatory properties of stem cells and its therapeutic implication in allergic airway disease. Furthermore, we will discuss mechanisms by which stem cells inhibit allergic airway inflammation via immunomodulation from a Th2- to a Th1-biased response. (Allergy Asthma Respir Dis 2016;4:167-173)

진행성 두경부 상피세포암 환자에서 소분할 방사선조사 후의 치료반응 평가

김원택(Won Taek Kim),기용간(Yong Kan Ki),남지호(Ji Ho Nam),김동현(Dong Hyun Kim),조규섭(Kyu Sup Cho),이진춘(Jin Choon Lee),이병주(Byung Joo Lee),김동원(Dong Won Kim) 대한방사선종양학회 2009 Radiation Oncology Journal Vol.27 No.2

목 적: 근치적 치료가 힘든 두경부 진행암 환자들을 대상으로 시행된 소분할 방사선조사의 치료반응 정도를 객관적 으로 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. Purpose: This study was performed to objectively evaluate the rate of tumor response to hypofractionated radiotherapy for advanced squamous cell carcinomas of the head and neck. Materials and Methods: Thirty-one patients with advanced squamous cell carcinoma of the head and neck, who were treated by hypofractionated radiotherapy with 3 Gy per fraction for palliative purpose between 1998 and 2008, were reviewed retrospectively. Every tumor-volume was measured and evaluated from CT (computed tomography) images obtained before and 2∼3 months after radiotherapy. The radiation toxicity was assessed during and after radiotherapy. A statistical analysis was performed to investigate overall survival, progressionfree survival, and the prognostic factors for survival and response. Results: The median age of the study patients was 70 years. In addition, 85% of the patients were in stage 4 cancer and 66.7% had an ECOG performance status of 1∼2. The mean tumor-volume was 128.4 cc. Radiotherapy was administered with a total dose of 24∼45 Gy (median: 36 Gy) over 10∼25 days. Twenty-nine patients were treated with 30 Gy or more. The observed complete response rate was 12.9% and the partial response rate was 61.3%. Median survival time was 8.9 months and the 1-year progression-free survival rate was 12.9%. The treatment response rate was confirmed as a prognostic factor in the rate of survival. The primary site, stage, tumor-volume, radiotherapy field and overall radiation-dose showed a significant relationship with survival and treatment response. No grade 4 toxicity was observed during and after radiotherapy. Conclusion: There was an objective tumor-regression in about 74% of patients treated by hypofractionated radiotherapy. Further evaluation is needed to select the appropriate fraction-size and patient who may require the additional radiotherapy.

근치적 방사선치료에 완전반응을 보인 경부 림프절에서의 재발 양상 및 그 의의

남지호(Ji Ho Nam),김원택(Won Taek Kim),기용간(Yong Kan Ki),김동현(Dong Hyun Kim),최영진(Young Jin Choi),조규섭(Kyu Sup Cho),이진춘(Jin Choon Lee),이병주(Byung Joo Lee),김동원(Dong Won Kim) 대한방사선종양학회 2010 Radiation Oncology Journal Vol.28 No.1

목 적: 진행된 두경부암 환자들에서 근치적 방사선치료 후 완전반응을 보인 경부 림프절 병변에서의 재발 빈도와 양상을 확인하고, 이의 임상적 의미를 알아보고자 이 연구를 진행하였다.대상 및 방법: 1987년부터 2008년까지 원발성 두경부 상피세포암종 및 경부 림프절 종대 병변에 대해 근치적 방사선치료를 받았던 환자들의 임상자료를 분석하였다. 이들 중 경부 림프절 병변에 충분한 방사선조사를 받은 후 완전반응으로 평가된 환자들을 최종 연구대상으로 선정하였다. 대상 환자들의 주기적 영상자료를 바탕으로 경부 림프절에서의 재발 빈도와 양상을 확인하였다. 아울러 재발률과 관련된 예후인자들도 분석하였다.결 과: 방사선치료 후 경부 림프절에서 완전반응으로 평가된 환자들은 73명이었다. 이들의 추적관찰 기간 동안의재발률은 19.2%였다. 원발 병변에서도 완전반응을 보인 55명에서의 경부 재발률은 5.5%였다. 경부 재발의 80%이상이 3년 이내에 확인되었으며, 47%에서 원발 병변의 재발이나 진행과 관련이 있었다. 치료 후 원발 병변의 반응 정도와 방사선 모의치료 방법이 경부 림프절 재발률과 관련 있었다.결 론: 방사선치료 후 원발 병변 및 경부 림프절 병변에서 완전반응으로 평가된 환자들에서의 경부 림프절 재발률은 약 5%로, 이들에서는 계획된 림프절 절제술 없이 정기적인 추적관찰이 가능할 것으로 판단된다. Purpose: This study was performed to examine the neck failure patterns after a complete response (CR) to definitive radiotherapy for advanced head and neck cancer patients, as well as evaluate the clinical ignificance of the results of this study. Materials and Methods: Between 1987 and 2008, the clinical data of patients who had been treated with radical radiotherapy for primary squamous cell carcinomas and enlarged cervical lymph nodes was analyzed retrospectively. Ultimately, the cases that showed CR of the cervical lymph node lesions to full-dose radiotherapy were included in this study. The recurrent rate and sites in the cervical lymphatic area were evaluated periodically by radiologic imaging studies, along with some factors which might have affected the rate of recurrence. Results: A total of 73 patients who achieved CR in neck area after radiotherapy were included in this study. The rate of subsequent neck failure among those patients was 19.2%. There was only a 5.5% failure rate in the 55 patients who underwent radiotherapy in their primary site. Eighty percent of the recurrent cases were found within 3 years (median follow-up, 68 months). The majority of neck recurrent cases (47%) were accompanied with the failure of the primary lesions. The initial response of the primary site and the method of radiotherapy simulation were significant prognostic factors associated with the nodal recurrence rate. Conclusion: The recurrence rate of cervical nodes in patients with CR to radiotherapy in the primary site and neck area was about 5%. These patients could be followed up with close observation without a planned neck dissection.

안와를 침범한 상악동 악성종양에서 안구 보존을 위한 내시경의 역할

조규섭,노환중 부산대학교 병원 암연구소 2008 부산대병원학술지 Vol.- No.24

Background and Objectives: The periorbita has been regarded as the crucial structure in decision of orbital exenteration in the patients with paranasal malignancies. The mass beyond the thickened periorbita on T2-weighted images was considered to be a positive finding of orbital invasion. The purpose of this study is to evaluate the oncological safety of endoscopic removal of infiltrated tumor onto the periorbita but not transgress into orbital fat. Patients and Methods: Five patients of advanced maxillary cancer, showing bony orbital wall destruction and infiltration onto the periorbita but not transgress into orbital fat, underwent partial or total maxillectomy. Preoperative Cl and MRI were performed in all cases and compared with intraoperative findings. The successful dissection between tumors and periorbita using bipolar nasal coagulation forceps and tumor forcep was performed under endoscopy. Results: The mean age was 54.4 (41-74) years. All tumors of five patients originated from maxillary sinus and extended to involve multiple different subsites according to AJCC (2002, 6^(th) ed.) Histopathology included four squamous cell carcinomas and one adenoid cystic carcinoma. Follow-up ranged from 30 to 121 months (mean 53.6 months). All cases showed no local recurrence on the periobita after endoscopic removal. One patient had local recurrence in the pterygopalatine fossa and the other had in the neck. Conclusion: Endoscopic removal of infiltrated tumor onto the periorbita using microdebrider, bipolar nasal coagulation forceps and tumor forceps can be oncologically safe technique in advanced maxillary cancer infiltrated onto the periorbita but not invaded into orbital fat.

포도상구균 초항원과 연관된 만성 비·부비동염의 병인에서 감마 인터페론 생산 T세포의 역할

김창수,조규섭,이현순,박희영,노환중 부산대학교 병원 암연구소 2008 부산대병원학술지 Vol.- No.24

Background and Objectives: The etiology and pathogenesis of chronic rhinosinusitis (CRS) is multifactorial and the role of infectious agents in CRS is not clear. S. aureus is the most frequent cultured pathogen in CRS and it expresses toxin, SEA, SEB and TSST-l, with superantigen (SAG) activity. Recently an importnat role of these staphylococcal toxins in CRS with nasal polyposis (CRSwNP) has been suggested. CRSwNP is a severe chronic inflammation characterized by massive infiltration of lymphocytes and eosinophils in the sinonasal mucosa and nasal polyp. However, there has been no further studies evaluating the properties of infiltrating T lymphocytes in CRSwNP and the cytokine profiles in activated T-Iymphocyte relating with SAGs. The aims of this study was to know what kind of T lymphocytes infiltrates in nasal mucosa and polyp tissue of CRSwNP, to analyze the cytokine profiles in infiltrating T cells, and to determine whether infiltrating T lymphocytes are specific for SAGs. Patients and Methods: Ethmoid sinus mucosa and polyp tissue samples were collected from 13 patients with CRSwNP and control sinus mucosa were obtained from 10 patient without CRS. Tissue infiltrating cells and T cells were isolated from tissue samples and flow cytometry, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, in vitro T lymphocyte stimulation with S. aureus toxin were performed. Results: The mean total CD3+ T cell count was significantly higher in the mucosa and polyp tissue of patients with CRSwNP compared with control mucosa. Most infiltrating T cells in mucosa and polyp tissue were activated type, expressing CD45RO. CD8+ T cells were significantly increased in mucosa and polyp tissue of patients with CRSwNP compared with CD4+ cells IFN-γ was highly expressed in infiltrating T cells in both mucosa and polyp tissue, whereas IL-10 was expressed a small amount and IL-4 was not expressed. IFN-γ levels were significantly higher than IL-4 and IL-10 when isolated T cells were stimulated with SAGs in vitro. Conclusion: CD8+ T-cytotoxic and IFN-γ producing Th1 cells could paly an important role in the CRSwNP if sinonasal chronic inflammation is induced by SAGs.

내시경부비동수술후 비음형대, 스펙트럼 및 비·부비동의 용적변화의 분석

김창수,공수근,이현순,조규섭,왕수건,노환중 대한이비인후과학회 2000 대한이비인후과학회지 두경부외과학 Vol.43 No.11