만성골수성백혈병 한국 치료 가이드라인-대한혈액학회

손상균 ( Sang Kyun Sohn ),정철원 ( Chul Won Jung ),조덕연 ( Deog Yeon Jo ),정준원 ( June Won Cheong ),대한혈액학회만성골수성백혈병연구회 ( Chronic Myelogenous Leukemia Working Party The Korean Societ ),김대영 ( Dae Young Kim ),이정옥 ( 대한내과학회 2015 대한내과학회지 Vol.88 No.4

Background/Aims: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). Methods: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. Results: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient`s age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. Conclusions: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.

HL6O 세포주의 분화 시 감소 특성을 보이는 Glutathione S-Transferase의 클로닝

김재철,박인규,이규보,손상균,김문규,김정철,Kim Jae Chul,Park In Kyu,Lee Kyu Bo,Sohn Sang Kyun,Kim Moo Kyu,Kim Jung Chul 대한방사선종양학회 1999 Radiation Oncology Journal Vol.17 No.2

목적 : HL60 세포주에서 PMA(phorbol 12-myrisate 13-acetate) 및 DMSO(dlmethyisulfoxlde) 에 의해 분화가 유도될 때 감소되는 특성을 보이는 K872 클론에 대한 염기 서열, 조직 분포, 단백 분리 등을 시행하였다. 재료 및 방법 QIA plasmid extraction kit(Qiagen GmbH, Germany)를 이용하여 사람의 모유두 세포 pBluescript phagemid cDNA library로부터 K872 클론을 추출하였다. Sanger's dideoxy nucleotide chain-termination method을 이용하여, 추출한 K872 클론의 염기 서열을 분석하였다. BLAST(Basic Local Alignment Search Tools) 프로그램으로 유전자은행의 염기 서열과의 상동성을 검색하였다. K872 클론으로 만든 probe로 다양한 인간 조직 및 암세포주로부터 분리한 RNA에 대하여 nothern blot을 시행하였다. His-Patch Thifusion expression system을 이용하여 대장균 배지에 0.1mM IPTG(Isopropyl-$\beta$-thlogalactopyranoslde) 를 첨가해서 결합단백의 유전자 발현을 유도하였다. 결합단백이 함유된 용출액을 SDS-PAGE에 걸어서 발현된 단백을 확인하였다. 결과 : K872 클론은 675개의 코딩 영역과 280개의 코딩과 관련없는 영역으로 구성된 1006개의 염기로 구성됨을 관찰하였다. 해독틀로 추정되는 부분은 시작 코돈을 포함하여 길6개의 아미노산을 형성하고 단백 산물의 분자량은 25,560 Da으로 추정되었다. 추정 아미노산 배열은 쥐의 glutathlone S-transferase kappa 1(rGSTKl) 의 아미노산 배열과 70$\%$의 상동성을 보였다. nothern blot에 따른 발현 양상은 심장, 수의근, 말초혈액 백혈구 등의 조직에서 높은 발현을 보였으며 방사선 내성과 관련지어 볼 때 대장암 및 흑색종 세포주에서 발현이 높았던 점은 특기할 만하였다. 결론 : 상동성 검색 결과 K872 유전자는 항암제 및 방사선 내성과 관련이 있는 rGSTK1에 대한 사람의 상동유전자로 사료되며 향후 이와 관련한 기능 분석이 필요할 것으로 사료된다 Purpose : By sequencing the Erpressed Sequence Tags of human 걸ermal papilla CDNA library, we identified a clone named K872 of which the expression decreased during differentiation of HL6O cell line. Materials and Methods : K872 plasmid DNA was isolated according to QIA plasmid extraction kit (Qiagen GmbH, Germany). The nucleotide sequencing was performed by Sanger's method with K872 plasmid DNA. The most updated GenBank EMBL necleic acid banks were searched through the internet by using BLAST (Basic Local Alignment Search Tools) program. Nothern bots were performed using RNA isolated from various human tissues and cancer cell lines. The gene expression of the fusion protein was achieved by His-Patch Thiofusicn expression system and the protein product was identified on SDS-PAGE. Results : K872 clone is 1006 nucleotides long, and has a coding region of 675 nucleotides and a 3' non-coding region of 280 nucleotides. The presumed open reading frame starting at the 5' terminus of K872 encodes 226 amino acids, including the initiation methionine residue. The amino acid sequence deduced from the open reading frame of K872 shares $70\%$, identity with that of rat glutathione 5-transferase kappa 1 (rGSTKl). The transcripts were expressed in a variety of human tissues and cancer cells. The levels of transcript were relatively high in those tissues such as heart, skeletal muscle, and peripheral blood leukocyte. It is noteworthy that K872 was found to be abundantly expressed in coloreetal cancer and melanoma cell lines. Conclusion : Homology search result suggests that K872 clone is the human homolog of the rGSTK1 which is known to be involved in the resistance of cytotoxic therapy. We propose that meticulous functional analysis should be followed to confirm that.

만성 림프구성 백혈병에 대한 최신 지견

조희정 ( Hee Jeong Cho ),손상균 ( Sang Kyun Sohn ) 대한내과학회 2021 대한내과학회지 Vol.96 No.3

Chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cell accumulation and highly variable clinical manifestations that range from an indolent to an aggressive course, is rare in Korea. Asymptomatic patients with early stage CLL can be followed up without treatment; however, those with active or advanced disease require treatment immediately after diagnosis, for symptom alleviation and prolonging survival. Previously, chemotherapy using cytotoxic agents was the only therapeutic option available for patients with CLL. Research has provided a deeper understanding of the pathophysiology of the disease, and novel agents such as monoclonal antibodies and small-molecule inhibitors that target specific sites on leukemic cells have been introduced. The advent of these new drugs has led to improved clinical outcomes in patients with CLL. Currently, Bruton’s tyrosine kinase inhibitors or B-cell lymphoma-2 inhibitors are recommended as frontline therapy, prior to the administration of cytotoxic agents or combination therapy with monoclonal antibodies. In this article, we review the diagnosis and prognosis of CLL, in addition to the clinical implications of the various therapeutic options. (Korean J Med 2021;96:195-208)

항과립구 항체 골수스캔을 이용한 다발성 골수종 병변의 평가 - 단순골 X-선검사 및 골스캔과의 비교

김동환,이재태,백진호,정진태,현동우,천경아,이영학,손상균,송홍석,이규보 ( Dong Hwan Kim,Jae Tae Lee,Jin Ho Baek,Jin Tae Jung,Dong Woo Hyun,Kyung Ah Chun,Young Hak Lee,Sang Kyun Sohn,Hong Seok Song,Kyu Bo Lee ) 대한핵의학회 1998 핵의학 분자영상 Vol.32 No.4

Purpose: Simple X-ray study and bone scan have limiitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow imrnunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement I:n multiple myeloma. Materials and Methods: In 22 patients (Male: 15, Female: 7) with multiple myeloma, we perforrned whole-body immunoscintigraphy using ' Tc-labelled antigranulocyte antibody (BW 250/183, Scintimum Granulozyt CIS, France) and compared the findings with those of simple bone radiography and Tc-MDP bone scan. Abnonnal findings in bone marrow scintigraphy were, considered to be present in case of expansion of peripheral bone marrow or focal photan defect in axial bones. Results: Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone rnarrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiography(58 sites, 47%) or bone scan(40 sites, 32%). Fifty-one (41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Conclusion: Bone marrow scan using Tc-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray ar bone sean in patients with multiple myeloma. (Korean J Nucl Med 1998;32:354-64)

폐결핵으로 오인된 역형성 거대세포 림프종 1례

현동우,박재용,강태경,박기수,박태인,김창호,손상균,권건영,이규보,정태훈,권삼,Hyun, Dong-Woo,Park, Jae-Yong,Kang, Tae-Kyung,Park, Ki-Soo,Park, Tae-In,Kim, Chang-Ho,Sohn, Sang-Kyun,Kwon, Kun-Young,Lee, Kyu-Bo,Jung, Tae-Hoon,Kweon, Sam 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.1

저자들은 발열, 체중감소 등의 증상과 흉부 X-선 사진상 폐경화의 소견이 있었던 환자에서 폐의 병변이 역형성 거대세포 림프종으로 추측되는 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Anaplastic large cell lymphoma(ALCL) is a recently recognized large cell lymphoma characterized by large pleomorphic cells, with prominent nucleoli, expressing the CD30(Ki-1) antigen. It is often misdiagnosed as metastatic carcinoma, malignant histiocytosis or Hodgkin's disease. Primary pulmonary ALCL is extremely rare although it frequently involves extranodal sites, e.g. skin, bone, gastrointestinal tract, soft tissue and lung. We report a case of ALCL suspected as primarily involving lung.

단일 폐병변에서 T1-201 SPECT 를 이용한 악성 종양의 감별진단

이규보(Kyu Bo Lee),이재태(Jae Tae Lee),손상균(Sang Kyun Sohn),천경아(Kyung Ah Chun),안병철(Byeong Cheol Ahn),김동환(Dong Hwan Kim),김창호(Chang Ho Kim),박재용(Jae Yong Park),정태훈(Tae Hoon Jeong),김천기(Chun K. Kim) 대한핵의학회 1998 핵의학 분자영상 Vol.32 No.2

N/A Purpose: T1-201 SPECT has been used in differentiating benign and malignant pulmonary lesions. While its sensitivity may be high, the specificity and predictive values are reported to be variable depending on the type of benign lung lesion. The purpose of this study was to prospectively assess the efficacy of T1-201 SPECT for differentiating benign and malignant single pulmonary lesions in a population with a high prevalence of begin pulmonary lesions, especially, tuberculosis. Materials and Methods: One-hundred thirty-three patients, having 89 malignant and 44 benign lesions(23 active tuberculosis, 5 inactive tuberculosis, 3 aspergilloma, 3 focal pneumonia, 2 thymoma, and 8 others), were imaged using a dual-headed system at 15 minute(early) and 3 hour (delayed) following administration of 111MBq T1-201. The images were read visually and lesion-to-background ratios(L/B) were obtained from transverse tomographic slices. Retention index was expressed as [(delayed L/B-early L/B) ÷ early L/B]. Results: 82/89(92%) and 83/89(93%) of the malignant lesions were visually positive on the early and delayed images, and 27/44(61%) and 26/44(59%) of the benign lesions wefe also between the mean L/B's of the malignant and benign lesions, L/B was not useful for differentiating the two due to a large overlap. There was no difference in retention indices. Conclusion: Despite of its high sensitivity, the specificity of T1-201 SPECT was unacceptably low in patients with active benign lesions. The positive and negative predictive values for lung cancer in a population with a high prevalence of the benign single pulmonary lesion was only marginal.

특발성 혈소판 감소성 자반증(ITP) 환자에서 복강경 비장절제술

박종훈(Jong Hoon Park),최규석(Gyu Seog Choi),손상균(Sang Kyun Sohn),윤영국(Young Kook Yun),전수한(Soo Han Jun) 대한외과학회 2000 Annals of Surgical Treatment and Research Vol.59 No.1

자가면역성 갑상선질환에서의 혈청 Thyrotropin - Binding Inhibiting Immunoglobulin치

이규보(Kyu Bo Lee),이재태(Jae Tae Lee),손상균(Sang Kyun Sohn),장대성(Dae Sung Jang),안병철(Byeong Cheol Ahn) 대한핵의학회 1996 핵의학 분자영상 Vol.30 No.1

N/A In order to evaluate the significance of thyrotropin-binding inhibiting immunoglobulin (TBII) in the patients with autoimmune thyroid diseases, the authors investigated 402 cases of Graves' disease and 230 cases of Hashimoto's thyroiditis comparing 30 cases of normal healthy adult at Kyung Pook University Hospital from February 1993 to August 1994. The TBII was tested by radioimmunoassay and assesed on the dynamic change with the disesase course, thyroid functional parameters, and other thyroid autoantibodies; antithyroglobulin antibody(ATAb) and antimicrosomal antibody(AMAb) including thyroglobulin. The serum level of TBII was 40.82±21.651(mean±SD)% in hyperthyroid Graves' disease and 8.89±14.522% in Hashimoto's thyroiditis and both were significant different from normal control of which was 3.21±2.571%. The frequency of abnormally increased TBII level was 92.2% in hyperthyroid Craves' disease, 46.7% in euthyroid Graves' disease or remission state of hyperthyroidism, and 23.9% in Hashimoto's thyroiditis. The serum levels of increased TBII in Graves' disease were positively correlated with RAIU, serum T3, T4, and FT4, but negatively correlated with serum TSH(each p〈0.001). The TBII in Graves' disease had significant positive correlation with serum thyroglobulin and AMAb, but no significant correlation with ATAb. In the Hashimoto's thyroiditis, the serum levels of TBII were positively correlated with RAIU, serum T3, TSH and AMAb, but not significantly correlated with serum T4, FT4, thyroglobulin and ATAb. Therefore serum level of TBII seemed to be a useful mean of assessing the degree of hyperthyroidism in Graves' disease and correlated well with thyroidal stimulation. The serum level of TBII in Hashimoto's thyroiditis is meaningful for the degree of both functionl abnormality reflecting either hyperfunction or hypofunction and the immunologic abnormality.

Thallium-201 을 이용한 세포막 Na+-K+ ATPase 활성도 측정 ; Rubidium-86 측정법과의 비교

이규보(Kyu Bo Lee),이재태(Jae Tae Lee),손상균(Sang Kyun Sohn),이인규(In Kyu Lee) 대한핵의학회 1998 핵의학 분자영상 Vol.32 No.2

N/A Purpose: Na+-K+ ATPase Activity has beem estimated by the degree of inhibition of cation transport by cardiac glycosides (ouabain) using Rb-86 as a substrate. The biological characterist- Isc of T1-201 is known to be simiIar to those of potassium as a transport substrate in the presence of glucose, insulin or phobol myristate acetate (PMA). The purpose of this study was to measure ouabain sensitive Na+-K+ ATPase activity using T1-201 and compare with that using Rb-86. Materials and Methods: Smooth muscle cells isolated from rat aorta or human placental umbilical artery were cultured, and used to measure cellular Na+-K+ ATPase activity. Na+-K+ ATPase activity was measured as a percentage decrease in cellular uptake of T1-201 or Rb-86 by ouabain under the presence of glucose, insulin or PMA in media. Results: Na+-K+ ATPase ase activity measured with T1-201, as a transport substrate, was not different from those measured with Rb-86 in rat or human smooth muscle cell preparation. Incubation with high concentration glucose resulted in about 30% decrease in enzyme activity. In contrast, insulin or PMA resulted in 50-70% or 28% increases from baseline activity, respectively. Conclusion: These results suggests that T1-201 could replace Rb-86 in measurement of ouabain sensititive Na+-K+ ATPase activity in vitro. High level of glucose concentration decreased cellular Na+-K+ ATPase activity, but insulin or PMA increased it.

방위산업 적격심사와 원가의 하방경직성

이진식(Lee, Jin Seek),윤윤석(Youn, Youn Suck),손상균(Sohn, Sang Kyun) 한국회계정보학회 2014 한국회계정보학회 학술대회발표집 Vol.2014 No.2

정부는 조달계약을 체결할 때 적격심사제도를 통해 입찰가격과 비가격요인(계약이행실적, 기술능력, 경영상태)을 종합적으로 고려하여 최적격 업체를 선별함으로써 조달실패의 위험을 감소시키고자 한다. 그러나 선행연구에서는 방위산업분야에서 적용하고 있는 적격심사의 비가격 평가항목이 방위산업의 특성을 제대로 반영하지 못하여 적격업체 선별기능이 미흡하다고 주장하고 있다. 따라서 본 연구에서는 적격심사제도의 문제점을 제기하고 있는 선행연구의 주장에 대한 실증분석을 하고자 한다. 이를 위해 적격심사의 비가격 평가항목이 부실업체를 제거하는 통제메커니즘으로 제대로 작동하고 있는지를 직접노무비 원가의 하방경직성을 이용하여 실증 분석하였다. 실증분석 결과에 따르면 적격심사기준 중 비가격 평가항목인 계약이행실적, 기술능력, 경영상태는 모두 직접노무비 원가의 하방경직성과 통계적으로 유의한 양(+)의 값으로 나타났기 때문에 정부가 무기체계의 조달을 위한 위임계약을 체결할 때 사전에 적용하는 적격심사제도는 역선택에 의한 대리인 문제를 완화시키는 것으로 볼 수 있다. 따라서 현행 방위산업분야에서 적용하고 있는 적격심사의 비가격 평가항목은 부실업체를 선별하는 기능이 제대로 작동하고 있다고 판단이 된다. 향후 정부는 무기체계 조달을 위한 위임계약에서 적격심사제도의 적용 범위를 확대하기 위한 다양한 정책을 수립한다면 방위산업분야의 오래된 과제이면서 시급히 해결해야하는 대리인 문제를 완화할 수 있을 것이다.본 연구는 다음과 같은 측면에서 유용성이 있다. 첫째, 적격심사와 대리인 문제의 상호작용변수를 이용함으로써 적격심사제도가 방위산업에서 원가의 하방경직성을 완화하여 대리인 문제를 완화하는 직접적이고 실증적인 증거를 제시하였다. 둘째, 대리인 문제와 관련된 질적인 측면의 대리변수를 실증분석에 이용하였다. 대리인 문제와 원가의 하방경직성에 관련된 선행연구에서 주로 계량적인 변수들을 이용하였다. 그러나 본 연구에서는 대리인 문제와 관련된 변수를 측정함에 있어서 대리인들의 질적인 특성이 반영된 변수를 이용하였다는 점에서 중요한 의미를 부여할 수 있다. Government would like to mitigate the risk of procurement failure by screening the proper firms. When closing a procurement contract, government considers the overall bid price and nonprice factors(previous contract performance, technical capability, and finance situation). But in the prior literature nonprice factors of Qualification Examination have not been selected weak firms very well in the defense industry. So in this study we are examining whether the nonprice factors of Qualification Examination are playing an important role to screen the weak firms through the analysis on the relation between Direct Labor Cost stickiness and nonprice factors of Qualification Examination. we expect nonprice factors of Qualification Examination to reduce the agency problem and therefore predict that nonprice factors mitigate the positive association between the agency problem and cost asymmetry. According to the empirical results, Our findings are consistent with the predictions. We find strong evidences that Direct Labor Cost asymmetry is positively associated with nonprice factors on Qualification Examination due to the agency problem, as measured by a previous contract performance, a technical capability, and a finance situation. Finally we conclude that nonprice factors of Qualification Examination could be screening weak firms properly. if Government extend the range of the application, agency problem should be reduced in the future when closing procurement contracts. The contributions of this study are as followings. First, it shows the empirical evidences that nonprice factors of Qualification Examination mitigate the cost stickiness with an agency problems in defense industry. Second, it used agency problem proxies which are a previous contract performance, a technical capability, and a finance situation in quality