원발성 폐암에서 LKB1 단백질 발현 소실에 따른 임상 양상 및 조직병리학적 특성

황기은 ( Ki Eun Hwang ),조향정 ( Hyang Jeong Jo ),이강규 ( Kang Kyoo Lee ),심혁 ( Hyeok Shim ),송정섭 ( Jung Sub Song ),신정현 ( Jeong Hyun Shin ),신성남 ( Seong Nam Shin ),박성훈 ( Seong Hoon Park ),홍경만 ( Kyeong Man Hong ) 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.64 No.5

연구배경: LKB1 (STK11)유전자는 Peutz-Jeghers syndrome에서 생식세포 돌연변이가 있으면 소화기와 폐를 포함한 타 장기의 암 발생 위험도가 증가한다고 알려져 있으며, 또한 종양 억제 기능이 있다고도 알려지고 있다. 하지만 현재까지 폐암에서 LKB1 유전자의 생물학적 기능이 명확하게 밝혀져 있지 않아, 저자들은 폐암조직에서 LKB1 단백질 발현소실과 임상양상 및 조직병리와의 연관관계를 알아보고자 하였다. 방법: 1998년 3월부터 2006년 3월까지 본원에 내원하여 원발성 폐암으로 진단받고 근치적 절제술을 시행 받은 77명의 환자를 대상으로 하였다. 파라핀에 포매된 조직을 택하여 면역조직화학염색법으로 LKB1 단백질 발현을 확인하였고, 정상 기관지 상피세포 세포질에서의 단백질 발현과 비슷한 정도의 발색을 갖는 종양세포가 전체 종양에서 30% 이상인 경우를 양성으로 판정하였다. 결과: LKB1 발현 양성은 40% (31/77)였고, 남성, 흡연, 편평상피암인 경우에 LKB1 발현 음성률이 통계적으로 유의하게 높았다. 종양위치가 중앙부위일수록 LKB1 발현 음성률이 증가하는 경향이 있으며, 종양 위치가 말초 부위인 경우 흡연력이 있는 군에서 LKB1 발현 음성률이 통계적으로 유의하게 높았다. TNM 병기가 진행할수록 LKB1 발현 음성률이 증가하는 경향이 있었으며, T2 병기 이상, N 병기가 진행할수록 LKB1 발현 음성률이 높아지는 경향이 있었으나, 통계적 유의성은 보이지 않았다. 결론: 원발성 폐암환자에서 LKB1 발현소실은 성별, 흡연력, 조직병리 형태와 의미있는 상관관계를 보였으나, 예후인자로서의 의의는 찾지 못했다. 하지만 환자의 숫자가 적어 추후의 연구가 이루어져야 할 것으로 사료된다. Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was>30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient`s lung cancer tissue samples will be needed to confirm this. (Tuberc Respir Dis 2008;64:362-368)

확장기 소세포폐암에서 1차 치료로서 Irinotecan + Cisplatin 복합요법의 임상적 결과

황기은 ( Ki Eun Hwang ),김소영 ( So Young Kim ),정종훈 ( Jong Hoon Jung ),박성훈 ( Seong Hoon Park ),박정현 ( Jung Hyun Park ),김휘정 ( Hwi Jung Kim ),김학렬 ( Hak Ryul Kim ),양세훈 ( Sei Hoon Yang ),정은택 ( Eun Taik Jeong ) 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.61 No.2

연구배경: Toptisomerase I 억제제인 irinotecan 과 소세포폐암 치료의 근간인 cisplatin의 복합화학용법을 확장기 소세포폐암 환자에게 1차 치료법으로 실시하여 반응률, 생존율 및 부작용을 확인하였다. 방법: 2002년 6월부터 2005년 2월까지 확진된 확장기 소세포폐암 환자 39명에게 irinotecan 60㎎/㎡, 제 1, 8, 15일째 cisplatin 60㎎/㎡ 제1일째에 28일 간격으로 4회 투여하였다. 결과: 반응률은 77%(완전반응 8%), 중앙생존기간은 14.8개월, 1-및 2-년 생존율은 60.9%, 27.6%였으며, 중앙 무진행생존기간은 8.4개월, 6-및 12-개월 무진행생존율은 75.0%, 18.8%였다. WHO grade 3 이상의 부작용은 백혈구 감소증 23%, 설사 26%였으나, 심한 설사때문에 2명은 치료방법을 바꾸었고, 1명은 사망하였다. 결론: Irinotecan과 cisplatin 복합화학요법은 확장기 소세포폐암 환자의 1차 치료법으로 유용하며, 부작용으로서 설사에 대해서는 치명적일수 있으므로 심각한 주의가 요망된다. Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan 60㎎/㎡ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin 60㎎/㎡ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity. (Tuberc Respir Dis 2006; 61: 143-149)

성인에서 횡격막마비로 오인한 우엽간 횡격막탈장 1예

박정현 ( Jung Hyun Park ),황기은 ( Ki Eun Hwang ),김소영 ( So Young Kim ),김학렬 ( Hak Ryul Kim ),양세훈 ( Sei Hoon Yang ),김휘정 ( Hwi Jung Kim ),정은택 ( Eun Taik Jeong ) 대한결핵 및 호흡기학회 2010 Tuberculosis and Respiratory Diseases Vol.68 No.5

Diaphragmatic paralysis can be demonstrated through diaphragmatic elevation on chest X-ray after thoracic Lung surgery or the placement of chest tubing. Additional causes of diaphragmatic paralysis are iatrogenic, mass, atelectasis, etc. For the diagnosis of diaphragmatic paralysis, it required some studies (fluoroscopy, computed tomography [CT], magnetic resonance imaging). Diaphragmatic hernia of the Liver is a rare clinical entity, usually found after trauma in adults. Congenital diaphragmatic hernia in neonates requires surgery. Non-traumatic diaphragmatic hernia of the Liver in an adult is a rare right-sided diaphragmatic hernia. On developing any symptoms, surgery must be performed. When diaphragmatic hernia is incidentally found in adults without trauma, it is placed under observation for a time period. We diagnosed the diaphragmatic herniation of a right hepatic Lobe by 16-slice CT scan without surgery.

이달의 X-선 : 경부 대상포진에 의한 횡격막 신경 마비 1예

김소영 ( So Young Kim ),황기은 ( Ki Eun Hwang ),정종훈 ( Jong Hoon Jung ),박정현 ( Jung Hyun Park ),김휘정 ( Hwi Jung Kim ),김학렬 ( Hak Ryul Kim ),양세훈 ( Sei Hoon Yang ),박현영 ( Hyun Young Park ),정은택 ( Eun Taik Jeong ) 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.61 No.1

저자들은 경부 대상포진 후 횡격막 마비 1예를 경험 하였기에 문헌 고찰과 함께 보고하는 바이다. Herpes zoster is well-known viral disease in immune compromised that produces inflammatory lesions in the posterior root ganglia and is characterized clinically by pain and skin eruptions along the distribution of the affected ganglia. However, motor involvement after a herpes zoster is an uncommon complication. We report a case of diaphragmatic paralysis that occurred after a herpes zoster in 63-year-old woman. The diaphragmatic paralysis occurred one month after the typical herpes zoster eruptions affecting the C3 and C4 dermatomes in the right neck, shoulder and back area. (Tuberc Respir Dis 2006; 61: 80-82)

증례 : 호흡기 ; 원인 미상의 호산구성 기관지내 점액박힘에 의한 폐쇄성 폐렴 1예

정재완 ( Jae Wan Jung ),황기은 ( Ki Eun Hwang ),손기창 ( Ki Chang Sohn ),임병훈 ( Byung Hun Lim ),조경화 ( Kyung Hwa Cho ),김학렬 ( Hak Ryul Kim ),정은택 ( Eun Taik Jeong ) 대한내과학회 2015 대한내과학회지 Vol.89 No.6

We report an unusual case of obstructive pneumonia due to an unknown eosinophilic mucoid impaction of the bronchi (MIB). A 54-year-old woman visited our hospital for investigation of abnormal shadows visible on a chest radiograph. Chest computed tomography and bronchoscopic examination revealed pneumonia due to MIB. Histopathological examination of biopsied mucosal tissue revealed extensive eosinophilic infiltration. With the exclusion of medical diseases that can cause eosinophilia, pneumonia due to eosinophilic mucoid impaction of the bronchi was diagnosed. The cause of the eosinophilia remained unknown. The pneumonia and mucoid impaction resolved after oral steroid therapy. (Korean J Med 2015;89:699-703)

신장종양이 동반된 Birt-Hogg-Dube Syndrome

오수진 ( Su-jin Oh ),황기은 ( Ki-eun Hwang ),정은택 ( Eun-taik Jeong ),김학렬 ( Hak-ryul Kim ),최금하 ( Keum-ha Choi ),류대웅 ( Dae Woong Ryu ) 대한내과학회 2019 대한내과학회지 Vol.94 No.4

Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant disorder characterized by the formation of hair follicle tumors, kidney tumors, and pulmonary cysts with recurrent spontaneous pneumothorax. A 44-year-old woman visited Wonkwang University Hospital with mild dyspnea. A chest X-ray on admission revealed pneumothorax in both lung fields. Chest computed tomography (CT) revealed both pneumothorax and multiple, irregularly shaped, variable-sized cysts in both lung fields. Upon physical examination, white dome-shaped papules were observed on the face. Histological examination of the skin lesion confirmed fi-brofolliculoma, and genetic studies revealed a folliculin gene mutation. Abdominal CT revealed a 1-cm small solid renal mass at the lower pole of the right kidney. We surgically removed the renal tumor, and a histological diagnosis of oncocytoma was made. Here, we report a case of BHD that demonstrated all three clinical manifestations; this is the first case report of its kind in Korea. (Korean J Med 2019;94:379-382)

증례 : 호흡기 ; 신세포암으로 오인한 1 cm 크기의 원발성 편평상피세포 페암의 신전이 1예

신익상 ( Ik Sang Shin ),정덕은 ( Duk Eun Jung ),황기은 ( Ki Eun Hwang ),양세훈 ( Sei Hoon Yang ),정은택 ( Eun Taik Jeong ),최금하 ( Keum Ha Choi ),김학렬 ( Hak Ryul Kim ) 대한내과학회 2011 대한내과학회지 Vol.80 No.1

신장 종괴를 처음 발견하였을 때는 예후와 치료 방법이 달라질 수 있기 때문에 원발성 종양에 대한 고려, 영상학적 소견, 임상 소견을 충분히 고려하여 원발성 신장암인지, 전이암인지에 대한 구별이 필요하다. 저자들은 65세 남자가 좌측 하복부 통증을 주소로 내원하여 좌측 신세포암 의심하에 신 적출술을 시행하여 조직 검사에서 전이성 편평상피세포암으로 진단 후 우측 폐하부에 1 cm 크기의 폐결절 조직 검사 결과 원발성 폐암이 발견된 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Symptomatic renal metastasis from a primary lung malignancy elsewhere in the body is an uncommon feature in disseminated cancer. We report a case of a 1-cm primary squamous cell carcinoma (SCC) of the lung with renal metastasis initially misdiagnosed as primary renal cell carcinoma in a 65-year-old man who presented with left lower quadrant pain. (Korean J Med 2011;80:97-101)

폐암세포주에서 Heme Oxygenase-1의 억제가 Cisplatin의 항암제 감수성에 미치는 영향

김소영 ( So Young Kim ),김은정 ( Eun Jung Kim ),장혜연 ( Hye Yeon Jang ),황기은 ( Ki Eun Hwang ),박정현 ( Jung Hyun Park ),김휘정 ( Hwi Jung Kim ),조향정 ( Hyang Jeong Jo ),양세훈 ( Sei Hoon Yang ),정은택 ( Eun Taik Jeong ),김학렬 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.62 No.1

연구배경: 다양한 고형암에서 HO-1의 높은 발현이 알려져 있고, 그것의 항산화와 항세포고사의 역할로 인해 빠른 암종의 성장에 중요한 역할이 있음이 보고되고 있다. 대표적인 활성산소종 생성 항암제인 Cisplatin은 현재까지 폐암치료에 가장 광범위하게 사용되고 있으나, 여러 내성발생이 임상치료의 주요문제로 대두되고 있다. 저자들은 A549 폐암세포주에서 HO-1의 발현이 증가되었고 HO-1 활성억제제나 siRNA 방법을 통해 생존율의 의미 있는 감소와 세포고사가 유도됨을 보고한 바 있다. 이 연구의 목적은 A549 폐암세포주에 cisplatin 처리시 HO-1의 발현의 증가유무와 기전을 규명하고 실제 HO-1의 억제가 cisplatin에 의한 항암제 감수성을 증가시키는지를 알아보는데 있다. 방법: 비소세포폐암세포주인 A549, NCI-H23, NCI-H157, NCI-H460을 이용하였다. 세포독성은 MTT 방법으로 구하였고, HO-1, Nrf2, MAPK의 발현은 Western blotting으로 확인하였다. 또한 MAPK억제제들을 전처치한 후 cisplatin에 의해 유도된 Nrf2와 HO-1의 발현에 미치는 영향을 역시 Western blotting으로 관찰하였다. A549세포에 활성억제제인 ZnPP나 HO-1 small interfering RNA (siRNA)을 주입하여 cisplatin과의 병합요법시 생존율의 배가효과 유무를 MTT 방법으로 확인하였고, 이러한 효과가 ROS 형성과 HO-1의 발현변화와 관련되는지를 알아보기 위해 carboxy-H2DCFDA 방법과 Western blotting을 통해 각각 확인하였다. 결과: Cisplatin 처리시 다른 세포주에 비해 A549세포가 의의 있게 내성을 보였다. 10μM의 농도에서 시간 의존적으로 HO-1, Nrf2, MAPK의 발현이 증가하였고, MAPK 억제제들을 전 처치하였을 때 cisplatin에 의해 유도된 HO-1과 Nrf2의 발현이 억제됨을 확인하였다. HO-1의 활성억제제인 ZnPP와 HO-1 siRNA를 통해 HO-1 mRNA를 직접 억제하는 방법으로 cisplatin과 병합치료시 단독치료에 비해 의의 있는 생존율의 감소를 보였다. 이러한 효과는 활성산소종의 생성 증가와 HO-1의 발현억제에 의한 결과임을 확인하였다. 결론: Cisplatin 처리시 HO-1의 발현은 MAPK-Nrf2-HO-1의 경로를 통해 증가하였고, 부분적으로 치료에 대한 내성과 관련이 있었으며, ZnPP 등의 활성억제제나 siRNA를 통한 knock-down 방법으로 HO-1을 표적으로 억제하는 치료방법을 통해 cisplatin의 항암제 감수성을 증가시켰다. Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide (H2O2) generation was monitored fluoimetrically using 2`,7`-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin. (Tuberc Respir Dis 2007; 62: 33-42)

소세포폐암환자에서 진단된 VGCC 항체 양성인 Lambert-Eaton 근무력 증후군

김소영 ( So Young Kim ),오효정 ( Hyo Jeong Oh ),황기은 ( Ki Eun Hwang ),정종훈 ( Jong Hoon Jung ),김학렬 ( Hak Ryul Kim ),양세훈 ( Sei Hoon Yang ),조광호 ( Kwang Ho Cho ),정은택 ( Eun Taik Jeong ) 대한결핵 및 호흡기학회 2005 Tuberculosis and Respiratory Diseases Vol.59 No.4

증례 : 악성 식도협착에 있어 티타늄 제재의 금속제 확장형 인공식도삽관술 최근 경험 5예

손봉준 ( Bong Jun Son ),유종현 ( Jong Hyeon Yoo ),황기은 ( Ki Eun Hwang ),장남수 ( Nam Soo Chang ),김기택 ( Ki Taek Kim ),전우규 ( Woo Kyu Jeon ),정을순 ( Eul Soon Chung ),이상종 ( Sang Jong Lee ) 대한소화기학회 1997 대한소화기학회지 Vol.29 No.6

Endoscopic esophageal endoprosthesis is a safe and effective procedure for the palliative treatment of obstructive esophagogastric malignancy. However, the placement of conventional plastic esophageal endoprosthesis is difficult in some cases and this procedure is associated with significant complications such as perforation, hemorrhage & dysfunction of the prosthesis in the long term. The self-expanding metallic stents offer an attractive alternative to conventional esophageal stents. Ultraflex(TM) esophageal prosthesis is knitted from a single strand of Elastalloy(TM) wire, and undulates to conform with normal esophageal peristalsis, maintaining patency and promoting patients` comfort. Recently developed EsophaCoil(TM) esophageal prosthesis is unique in that it is a simple coil with close loops made from a single flat wire of nickel titanium alloy. Because the radical force of this material is much stronger than stainless steel, expansion time is therefore faster and the stent is able to dilate even extremely resistant strictures. We report our recent experience in five patients with malignant esophageal obstruction palliated with the new self-expandable titanium stent(Ultraflex(TM) and EsophaCoil(TM)).(Korean J Gastroenterol 1997;29:826-835)