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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)
복수의 감별에 있어 혈청과 복수내 CEA 및 CA19-9의 가치에 관한 연구
김선민 ( Kim Seon Min ),박경식 ( Park Gyeong Sig ),마상인 ( Ma Sang In ),김휘정 ( Kim Hwi Jeong ),유승박 ( Yu Seung Bag ),조준환 ( Jo Jun Hwan ),이재동 ( Lee Jae Dong ),이중건 ( Lee Jung Geon ) 대한내과학회 1992 대한내과학회지 Vol.42 No.4
1989년 4월 1990년 12월까지 본원 내과에서 입원하였던 복수 환자 81예를 대상을 그 원인 악성 질환에 의한 것인지 양성 질환에 의한 것인지를 감별하기 위해 혈청 및 복수내의 CEA, CA19-9의 농도를 측정 비교하여 그 임상적 의의에 대해 다음과 같은 결과를 얻었다. 1) 악성 질환에서의 CEA의 혈청내 평균치는 양성질환보다 의의있는 상승을 보였으며(p<0.05), 복수내 평균치 또한 유의한 상승을 보였다(p<0.01)> 2) CA19-9의 혈청과 복수에서의 평균치는 악성 복수군에서 현저한 상승을 보였으나 통계적 유의성은 없었다.(p>0.05). 3) 복수의 감별진다에 있어 CEA의 복수내의 민감도는 84%였으며 혈청에서는 71%이였으며 CA19-9는 복수내의 민감도가 68% 혈청에서는 60%로 CEA보다는 전체적으로 민감도가 낮았다. 4) 혈청과 복수에서 CEA 병합 검사시 민감도는 86%로 상승하였으며 CA19-9병합 검사시 민감도 또한 73%로 상승 하였으며 모두 병합 검사시 민감도는 92%로 의의있는 상승을 보였다. 5) 혈청내 CEA 복수내 CEA 혈청내 CA19-9 및 복수내 CA19-9 검사간에는 유의한 상관관계가 있었다(p<0.005, p<0.001). 이상과 같이 혈청과 복수에서의 CEA와 CA19-9 농도 측정은 복수의 원인이 악성 질환에 의한 것인지를 아는데 도움이 될 것으로 사료된다. Ascites may be caused by various benign and malignant disease, but it is sometimes difficult to determine whether it is caused by benign disease or malignant diseases. In order to determine whether CEA, CA 19-9 in ascitic fluid and serum assist in the diagnosis of malignant disease that causing ascites, we studied 38 cases of malignant ascites and 43 cases of benign ascites patients who were admitted to Seoul Adventist Hospital from April 1989 to December 1990. The results were obtained as follows: 1) The mean value of CEA in serum and ascitic fluid of the malignant ascites group were significantly higher than that of the benign ascites group in serum (p<0.05), in ascites (p<0.01). 2) The mean value of CA 19-9 in serum and ascitic fluid of the malignant ascites group was signficantly higher than that of the benign ascites group was significantly higher than that of the benign ascites group, there was no significance in statistical aspects(p>0.05). 3) The sensitivity of CEA was 81% in ascites, 78% in serum, the sensitivity of CA 19-9 was 63% in ascites, 65% in serum. 4) The sensitivity of CEA was increased to 87% in serum and ascites combinations, the sensitivity of CA 19-9 was also increased to 81% in serum and ascites combinations. The sensitivity was significantly elevated to 92% in case of all tumor marker combinations. 5) There was a significant correlations between serum CEA and ascites CEA, serum CA 19-9 and ascites CA 19-9. (p<0.01, in all cases) It was concluded that the measurement of serum and ascites CEA, CA 19-9 levels is useful lin differention between ascites caused by benign and malignant diseases. Combinantions of each tumor markers in serum and ascites were more accurate than single test.
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)
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)
노동효 ( Dong Hyo Noh ),김학렬 ( Hak Ryul Kim ),조경화 ( Kyung Hwa Cho ),김동 ( Dong Kim ),신성남 ( Seong Nam Shin ),신정현 ( Jeong Hyun Shin ),송정섭 ( Jung Sub Song ),황기은 ( Ki Eun Hwang ),김소영 ( So Young Kim ),김휘정 ( Hwi 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.67 No.2
Chemical pneumonitis induced by hydrocarbon aspiration is rare in Korea. Kerosene is a petroleum distillate with low viscosity and high volatility. We report two adult cases of chemical pneumonitis caused by the accidental aspiration of kerosene. They were treated successfully with antibiotics and systemic corticosteroids, and recovered without complications.
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.