폐암으로 오인된 이물질에 의한 기관지 육아종증 1예

정종훈,김소영,김휘정,김학렬,양세훈,정은택 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

악성 흉막삼출액에서 Bleomycin을 이용한 흉막유착설의 시술효과

박정현,김학렬,양세훈,정은택 圓光大學校 醫科學硏究所 2002 圓光醫科學 Vol.17 No.1

목적: 악성 흉막삼출액이 반복적이고 지속적으로 발생하는 경우, 호흡곤란, 흉통등의 증상을 유발시키므로 흉막경화제에 의한 흉막유착술을 시행할 수 있다. 흔히 사용되던 talc의 심각한 부작용이 보고되고 있고, doxycycline 주사제도 국내에서 발매되지 않고 있다. 이에 연자들은 항암제로 소개된 bleomycin을 이용한 흉막유착술의 단기와 중기효과, 부작용 및 생존율 등을 전향적으로 확인하였다. 방법: 2000년 1월부터 2001년 12열까지 원광대학교 부속병원에 내원하여 반복적이고 지속적인 악성 흉막삼출액으로 흉막유착술이 필요한 26명의 환자를 대상으로 특별한 전 처치 없이 bleomycin 60 unit를 식염수와 함께 흉강 내 주입 후, 1일 후의 흉관에 의한 배액량을 확인하고 부작용을 관찰하였으며, 1개월 후에 흉부 방사선상으로 재 저류 유무를 확인하였다. 또한 시술 반응군과 비반응군으로 나누어 중앙생존기간을 비교분석 하였다. 결과: 시술 1일 후 26예중 10예(38%)에서 배액이 없었고, 8예(31%)에서 배액량이 100ml이하였으며, 8예(31%)는 100ml이상이었으나 시술 전보다 감소하였으며 증가된 경우는 없었다. 유의할만한 부작용은 4예(고열 3예, 흉통 1예)에서 발생하였으나, 대증요업으로 조절되었다. 시술 1개월 후 흉부 방사선과 26예중 9예(35%)는 재 저류액이 없었고, 10예(38%)는 저류액이 있으나 시술 전보다 감소하였으며, 1예(4%)는 이전과 변화가 없었고, 6예(23%)는 시술 전보다 저류액이 증가하였다. 시술 후 단기 및 중기효과를 반응군과 비반응군으로 나누어 중앙생존기간으로 양군간을 비교하였을 때, 반응군에서 연장이 되었으나 통계적으로 유의한 차이는 없었다. 결론: 이상의 결과로서 bleomycin에 의한 흉막유착술은 다른 경화제보다 특별한 전 처치가 필요 없는 간편하고, 비교적 부작용이 적은 안전한 방법이며, 효과적인 치료성적을 보이는 시술로 사료된다. Background : Malignant pleural effusions are common and significant problems in patients with advanced malignancy. Repeated thoracentesis provides temporary symptomatic improvement, but most patients progressively cause dyspnea or pleuritic pain. So pleurodesis with sclerosing agent is effective as a palliative treatment. There are many drugs used as pleural sclerosing agents. But doxycycline hasn't been used in Korea since 1999. And recently talc has been reported serious side effects. In this study, pleurodesis with bleomycin was prospectively investigated for its short term and middle period effects and its side effects. Methods : Twenty-six patients with malignant pleural effusion were prospectively analyzed to estimate the effects of bleomycin pleurodesis. Without special management before the procedure, 60 units of bleomycin in 50-100ml of normal saline were instilled into the pleural space via a small bore catheter(8-10 F). Andthen repeated positional changes and rotations were done for 2 hours. We measured the drainage amount and evaluated the side effects after 24 hours and checked the existence of the effusion by chest radiography after 1 month. Results : After 24 hours, the drainage amount showed that the responder group(none or ≤ 100ml) was 69%, and that the nonresponder group(> 100ml) was 31%. Side effects (high fever in 3 cases and severe pleuritic pain in 1 case) were 15%(4/26), but patients recovered easily by symptomatic management. After 1 month, chest radiography showed that the response rate(complete or partial response) was 73%. Differences of survival times between responder and nonresponder group was not statistically significant. Conclusions : We are suggest that bleomycin as a pleural sclerosing agent is a relatively simple, safe and effective agent. But a prospective study with a larger number of patients must be warranted.

자발성 기흉을 동반한 폐림프관평활근종증 1예

안용환,정종훈,김소영,김휘정,김학렬,양세훈,최순호,문형배,조향정,정은택 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

흡연에 의한 급성 호산구성 폐렴 2예

박종빈,김학렬,주현준,유태양,신성남,신정현,송정섭,황기은,김소영,양세훈,정은택 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

최근 흡연을 시작한 젊은 성언에서 급성 호산구성 폐렴의 발생에 대한 증례가 보고되고 있다. 급성 호산구성 폐렴은 대개 발열을 동반하기 때문에 초기에는 감염성 폐렴으로 잘못 진단, 치료되는 경우가 많다. 아직 정확한 병태 생리 및 조직학적 소견은 밝혀져 있지 않지만 병력 청취 및 임상 양상, 방사선 소견의 관찰을 통해 급성 호산구성 폐렴을 의심하고, 진단을 위해 기관지 폐포 세척액 검사를 시행한다면 좀 더 쉽게 진단 내릴 수 있을 것이다. 본 저자들은 최근 처음 시작한 흡연에 의해 발생한 급성 호산구성 폐렴을 진단하고, 스테로이드를 투여하여 성공적으로 치료한 환자 2예를 경험하였기에 이를 문헌 고찰과 함께 보고하는 바이다. Acute eosinophilic pneumonia(AEP) is characterized by acute febrile respiratory illness associated with diffuse pulmonary infiltration and pulmonary eosinophilia. The specific etiology for acute eosinophilic pneumonia is elusive. By some investigators, cigarette smoking is suggested as a causative substance which can cause AEP. In recent, the authors experienced two cases of AEP following cigarette smoking. Both cases had characteristic features including age around 20 years, new onset smoking before occurance of AEP, diffuse infiltration on chest radiography, pulmonary eosinophilia based on bronchoalveolar lavage and acute improvement after steroid therapy. These clinical features are resemble with previous smoking induced AEP case reports. Base on these clinical features, cigarette smoking associated AEP could be diagnosed more easily.

Mutations of the LKB1/STK11 Gene in Non-Small Cell Lung Cancer with Loss of Heterozygosity

( Sei Hoon Yang ),( Leah E Mechanic ),( Rajbir Gill ),( Tatiana Dracheva ),( Seong Hoon Park ),( Jung Hyun Park ),( Hwi Jung Kim ),( Hak Ryul Kim ),( Eun Taik Jeong ),( Curtis C. Harris ),( Jin Jen ) 대한결핵 및 호흡기학회 2006 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.103 No.-

Afatinib Mediates Autophagic Degradation of ORAI1, STIM1, and SERCA2, Which Inhibits Proliferation of Non–Small Cell Lung Cancer Cells

Sei-Hoon Yang,Mi-Seong Kim,양세훈,김민석 대한결핵및호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drugresistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear.Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non–small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation.Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non–small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinibresistant non–small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR ). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+.Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.

Enhancing Anti-tumor Efficacy by Combination of WK0202 with Immune Checkpoint Inhibitors and Immunogenic Cell Death Inducer including Chemotherapy/Targeted Therapy

( Sei Hoon Yang ),( Hong-seob So ),( Sun Rock Moon ),( Tae Hwan Kwak ),( Hong Seob So ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0

Background/Aim Immune checkpoint inhibitors (ICIs) including anti-PD1, anti-PD-L1, and anti-CTLA-4 show promising therapeutic outcomes. However, ICI has a limited effect in some carcinomas. To overcome these shortcomings, ICI was combined with chemotherapy, targeted therapy or radiation therapy inducing immunogenic cell death (ICD). ICD involves the release of damage-associated molecular patterns (DAMPs) from dying tumor cells to activate tumor-specific immune responses. ICD also causes the release of tumor-associated antigens, destruction of physical barriers, and promoting immune cell re-penetration, which trigger adaptive immune cells to elicit an antitumor immune response. However, nonetheless, if the intratumoral environment surrounding cancer cells with high concentrations of lactate, TGF-b, HIF1/2, and VEGF, which favors cancer growth and metastasis, does not change, these therapeutic outcomes will be limited. WK0202, our drug candidate, does not directly induce ICD, but fundamentally changes the tumor microenvironment favorable for cancer growth and metastasis by modulating aerobic glycolysis. Therefore, our research aim is to demonstrate that the combination of WK0202 with ICD stimulation such as chemotherapy or targeted therapy and ICIs could induce even more anti-tumor efficacy. Methods WK0202, which is currently completed Phase 1 study by NADIANBIO Ltd., will be administered in combination with an immunotherapy in Phase 2 clinical trial. Using a preclinical mouse lung cancer model system, we examined the anti-tumor efficacy of triple combination consisted of ICI, ICD inducer, and WK0202. Anti-PD1 was used as ICI, and paclitaxel/carboplatin was used as ICD inducer. Results WK0202, when administered in combination with ICD and ICI, produced significantly higher anticancer effects than when each component was administered alone or when ICI and ICD were combined. Conclusions Therefore, our research suggests a possibility that the combination of WK0202 with ICD stimulation such as chemotherapy or targeted therapy and ICIs could induce even more clinical benefits in various cancer patients.

REVIEW : Molecular Basis of Drug Resistance: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Anaplastic Lymphoma Kinase Inhibitors

( Sei Hoon Yang ) 대한결핵 및 호흡기학회 2013 Tuberculosis and Respiratory Diseases Vol.75 No.5

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer

( Sei Hoon Yang ),( Leah E. Mechanic ),( Ping Yang ),( Maria Teresa Landi ),( Elise D. Bowman ),( Jason Wampfler ),( Daoud Meerzaman ),( Kyeong Man Hong ),( Felicia Mann ),( Tatiana Dracheva ),( Junya 대한결핵 및 호흡기학회 2006 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.103 No.-

Molecular Basis of Drug Resistance: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Anaplastic Lymphoma Kinase Inhibitors

Yang, Sei-Hoon The Korean Academy of Tuberculosis and Respiratory 2013 Tuberculosis and Respiratory Diseases Vol.75 No.5

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.