진행암 환자에서 Cisplatin 병용화학요법시 Ondansetron의 오심 구토 조절 효과

전의건,윤환중,길준영,조덕연,김삼용 최신의학사 1992 最新醫學 Vol.35 No.12

구인두 캔디다증에 대한 Fluconazole의 치료효과

전의건,윤환중,길준영,조덕연,김삼용 최신의학사 1993 最新醫學 Vol.36 No.5

백혈병 세포주에 대한 Biological Response Modifiers의 항암제 세포독성 증강효과

이윤영,전의건,길준영,윤일국,유관희,안병준,김삼용 충남대학교 약학대학 의약품개발연구소 1995 藥學論文集 Vol.11 No.-

To investigate the possibility of increased cytotoxicity of anticancer drugs, we treated human leukemia cells with combinations of anticancer drugs and biological response modifiers(BRMs). Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, we evaluated the chemosensitivity of 8 anticancer drugs (vincristine, vinblastine, adriamycin, cisplatin, etoposide, cytosine arabinoside, bleomycin, and cyclophosphamide), and the anticancer effects of 3 BRMs(interleukin-2, alpha interferon, and gamma interferon) combined with these anticancer drugs against human leukemia HL-60 and KG-l cells. The results were as follows; in the chemosensitivity of 8 anticancer drugs, VCR, VBL, ADR, and CPDD were effective, while VP-l6, ara-C, Bleo, and CYC produced less than 50% inhibition of HL-60 and KG-l cells lines. Among 3 BRMs investigated, all of them showed less than 20% inhibition of KG-l cell lines and none were effective against HL-60 cells. In the anticancer effects of 3 BRMs, all of them showed about 20% inhibitory effects against KG-l cells, but there were not any effects against HL-60 cells. All of the anticancer drugs markedly increased cytotoxic effects when they were combined with BRM. Especially, the ID_50 values of VCR, VBL and ADR when combined with BRMs decreased to 67~3%. These results demonstrate that some BRMs can markedly increase the cytotoxicity of VCR, VBL, ADR, CPDD, VP-l6, ara-C, Bleo, and CYC and suggest possible clinical usefulwess.

Cyclosporine에 혈액학적 반응을 보인 Refractory Anemia 1예

길준영,윤환중,전의건,오덕연,김삼용,김종완,박종우 大韓血液學會 1992 大韓血液學會誌 Vol.27 No.2

저자들은 refractory anemia로 진단받고 23개월간 지속적인 적혈구 수혈(매월 2units씩 총 47units)을 필요로 했던 58세 여자 환자에 cyclosporine을 투여하여 21개월간 혈액학적 반응 을 경험하였고 이 기간에는 수혈이 필요치 않았다. Refractory anemia의 발병기전은 아직 분명치 않으나 일부 환자에선 면역억제제에 반응함으로써 일부 면역기전이 작용한다고 생각된다. The myelodysplastic syndromes which encompass refractory anemia are characterized by ineffective hematopoiesis, refractory cytopenias, and an increased risk of leukemic transformation. No currently available treatment has been shown to be consistently effective in producing sustained improvement in hematopoiesis or in delaying leukemic evolution. Cyclosporine has been used for the therapy of patients with aplastic anemia. We report a case of refractory anemia who responded to cyclosporine(Sandimun®). A 58-year-old woman was admitted to the Chungnam National University Hospital for the evaluation of pancytopenia. Blood examination showed 2,600/㎣ of white blood cells, 5.9g/dL of hemoglobin, and 38,000/㎣ of platelets. Reticulocyte index was 0.2%. The levels of serum iron, iron-binding capacity, vitamin B_l2, and folic acid were in normal range. Bone marrow biopsy revealed hypercellularity, dysmyelopoiesis, dyserythropoiesis, myeloid hyperplasia. The hematologic findings were compatible with the diagnosis of refractory anemia and the diagnosis of aplastic anemia could be excluded. Treatment with oxymetholone(50㎎/day) and pyridoxine(300㎎/day) was started. Packed red cells transfusions(total of 47 units) were required over a period of 23 months. An oral cyclosporine(Sandimun®) therapy was started at a dosage of 300㎎ per day. One month after cyclosporine therapy hemoglobin level began to increase and reached 11.6g/dL after 12 weeks. The dose of cyclosporine was reduced to 200㎎ per day and discontinued after total of 19 weeks of therapy. Her hemoglobin level remained stable between 13 and 15g/dL without transfusion. After a 21 months of hematological remission, she was readmitted because of progressive dyspnea after undergoing a cataract operation 2 months ago. Despite transfusion of packed red cells and plateletpheresis to which she was refractory. Her hemoglobin level was around 3g/dL and platelet count decreased progressively. Retrial of cyclosporine(900㎎/day for 2 weeks) and a trial of GM-CSF(400㎍/day for 7 days) were of no benefit. She succummed to gastrointestinal and intraperitoneal bleeding. The exact mechanism of cyclosporine in this case is uncles but it is reasonable to ascribe the striking hematologic improvement to cyclosporine. As some reports showed responses to immunosuppressive therapy in refractory anemias, in some proportion of patients with refractory anemia, immune mechanism may be involved in the pathogenesis. The role of immunosuppressive therapy in refractory anemia should be further clarified.

진행암 환자에서 Cisplatin 병용화학요법 시 Ondansetron의 오심 구토 조절 효과

조문준,윤환중,전의건,길준영,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Ondansetron is a novel agent that selectively binds to the 5-hydroxytryptamine_3 receptor, and has been reported to have a prominent effect in the prevention of anti-neoplastic agent induced nausea and vomiting. Twenty solid tumor patients who were scheduled to receive cisplatin containing combination chemotherapy participated in a prospectively open-labeled study to evaluate the antiernetic efficacy and safety of ondansetron. The male to female ratio was 11 : 9 and median age was 49(16-70). The sites of primary neoplasms and number of patients were as following : head and neck 4, metastatic carcinoma of unknown primary site 3, stomach 3, osteosarcoma 2, ovary 2, esophagus 1, melanoma 1, penile 1, bladder 1, cervix 1, and extragonadal germ cell 1. Ondansetron was given as an 8mg loading dose IV before chemotherapy followed by 8mg IV every 8 hours until 24 hours after chemotherapy completion. Complete or major control(0 to 2 emetic episodes) of emesis was achieved in 17 of 20 patients(85%;complete 50%, major 35%) receiving ondansetron during the first 24hrs of chemotherapy. During the period of day 2 through clay 5 of chemotherapy, 14 of 20(75%) patients had complete or major control of emesis(complete 35%, major 35%). No severe side reactions were recorded in ondansetron treated patients, while mild to moderate headache was noted in 20% of patients. These results show that ondansetron is effective in the control of cisplatin induced nausea and emesis, and can be administered safely with minimal side effects.

급성골수백혈병에 대한 관해유도화학요법 후의 Granulocyte Colony-stimulating Factor의 효과

윤환중,최지영,전의건,길준영,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Granulocyte colony-stimulating factor(G-CSF) have been shown to hasten the recovery of neutropenia following anti-cancer chemotherapy. There are controversial opinions on the use of G-CSF in acute myelogenous leukemia(AML) because clonogenic studies have shown that G-CSF stimulates leukemic colonies as well as granulocyte colonies. In this study, we evaluated the effectiveness and safety of recombinant human G-CSF after induction chemotherapy with DAV regimen(Ara-C 100mg/㎡ day 1-8, Doxorubicin 45mg/㎡ day 3-5, VP-16 100mg/㎡ day 6-8) in 9 patients with AML. G-CSF therapy(200 ㎍/㎡/day) was begun 2 days after the end of chemotherapy and continued for 10 days. 17 AML patients who recieved the same chemotherapy before the onset of this study were used as historical control. G-CSF shortened the duration of granulocytopenia (less than 500/㎣) significantly (13 vs 23 days, p<0.001), but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, the duration of febrile episodes was shorter in the group treated with G-CSF( 5 vs 12 days, p=0.03). There was no evidence that G-CSF accelerated the regrowth of leukemic cells and the complete remission rates between the 2 groups were not different. These results show that G-CSF accelerates the recovery of granulocytopenia and shortens the febrile days after chemotherpy in patients with AML, without affecting the regrowth of leukemic cells.

백혈병의 분자생물학적 연구 -암유전자를 이용한 백혈병의 진단-

박철신,윤환중,전의건,길준영,조덕연,김삼용,이복수,백상기 大韓血液學會 1992 大韓血液學會誌 Vol.27 No.2

재생불량성 빈혈의 임상적 고찰

김삼용,길준영,전의건 충남대학교 의과대학 지역사회의학연구소 1991 충남의대잡지 Vol.18 No.2

A retrospective analysis of clinical data of 32 cases of aplastic anemia diagnosed at Chungnam National University Hospital from August 1985 to July 1991 was done. 1) The highest incidence of aplastic anemia was seen in the third decade and 25 cases of patients (78.2%) were below 40 years of age. The incidence decreased in older age groups. 2) Exposure to possible toxic agents were seen in 6 cases(18.8%), among which benzene was related in 2 cases(6.3 % ), herb drug in 2 cases(6.3 % ), acute viral hepatitis(type B) in 1 case(3.1 % ), antifungal agent in 1 case(3.1 % ). 3) Initially all patients were treated with oxymetholone with or without prednisolone and supportive care. Eleven(37.9 %) out of twenty-nine patients showed responses(CR: 17.2%, PR: 20.6%). Nine out of the eighteen patiens who did not respond to androgen therapy were treated with antilymphocyte globulin (ALG) plus methylprednisolone. Two patients(22.2 %) out of 9 showed complete responses. 4) Overall responses of present series of patients was 44.8 % (androgen± prenisolone therapy: 37.9%, ALG+ methylprednisolone: 6.9%). The actuarial survival of all patients at 72 months was 83.4%. The median survical rate of severe aplastic anemia(32 months) was similiar to that of moderate aplastic anemia(37 months). 5) Factors associated with favourable survival were male sex and presence of etiological factor. Since the prognosis of aplastic anemia in Korea is quite favorable, randomized controlled study would be needed to define the therapeutic roles of bone marrow transplantation of immunosuppressive therapy in patients with severe aplastic anemia in Korea.

Interleukin-1 수용체 길항제에 의한 만성골수성백혈병 집락형성 및 K562세포 증식 억제

조덕연,최지영,윤환중,전의건,길준영,김삼용,배윤수,최인성 大韓血液學會 1993 大韓血液學會誌 Vol.28 No.2

재생불량성 빈혈의 임상적 고찰

길준영 ( Gil Jun Yeong ),전의건 ( Jeon Ui Geon ),윤환중 ( Yun Hwan Jung ),김백수 ( Kim Baeg Su ),최용석 ( Choe Yong Seog ),조덕연 ( Jo Deog Yeon ),김삼용 ( Kim Sam Yong ) 대한내과학회 1993 대한내과학회지 Vol.44 No.3

연구배경 : 재생불량성 빈혈은 우리나라를 비롯하여 극동지역에서 호발하는 중요한 질환이며 우리나라 재생불량성빈혈 환자의 임상상은 서양과 차이가 있는 것으로 알려져 있다. 재생불량성 빈혈 환자를 임상적으로 관찰하여 생존기간과 예후인자등을 알아보고자 1985년 8월부터 1991년 7월까지 6년동안 충남대학교병원 내과에서 입원가료를 받은 재생불량성 빈혈 환자 32예에 대하여 분석하였다. 방법 : 모든 대상환자에 일차적으로 oxymetholone(50~100mg/d)을 경구 투여하였고 필요에 따라 prednisolone (5~10 mg/d)을 추가하였다. Androgen 요법에 반응이 없는 20예중 9예에 antilymphocyte globulin (20mg/kg/d)을 4일간 정맥주사 하였으며 동시에 methylprednisolone (20mg/kg/d)을 5일간 정맥주사 하였다. 결과 : 1) 연령별로는 21~30세가 12예 (37.5%)로서 가장 많았으며 40세 이하가 25예(78.2%)였다. 2) 원인을 추정할 수 없는 경우가 26예(81.2%)로 대부분을 차지하였고 원인을 추정할 수 있는 경우가 6예 (18.8%)였는데 한약제 2예(6.3%), benzene 2예 (6.3%), 항진균제 1예(3.1%), 급성간염 B형 1예(3.1%) 였다. 3) Androgen을 중심으로 한 치료에 31예 중 5예(16.1%)에서 완전방응을, 6예(19.4%)에서 부분반응을 보여 반응율은 35.5%이였다. Androgen 치료에 반응이 없었던 20예중 9예에 2차적으로 시행한 antilymphocyte globulin 면역조절요법에 2예(22.2%)에서 완전방응을 보여 전체 42%의 반응율을 보였다. 4) 초진시 중증 재생불량성 빈혈 환자 20예(64.5%)의 72개월 생존율은 79.3%, 중앙생존기간은 32(2~72+)개월이었다. 중등도의 재생불량성 빈혈 11예(37.5%)의 72개월 생존율은 90%, 중앙생존기간은 37(13~72+)개월이었다. 50 남자 환자에서 여자 환자보다 반응율이 더 높았고 (61.5% vs 27.8%, p<0.05). 원인추정이 가능했던 예에서 원인을 알수 없었던 예보다 더 높은 반응율을 보였다(66.7% vs 28%, p<0.05). 그러나 초진시의 혈소판수, 과립구수, 또는 교정 망상적혈구수는 치료반응에 영향을 미치지 못하였다(p>0.05). 결론 : 재생불량성 빈혈 환자 32예중 31예에서 androgendmf 중심으로한 고식적치료와 면역억제요법만으로도 72개월 생존율이 83.1%였으며 서양환자에서의 예후보다 훨씬 양호한 것으로 판단된다. 따라서 골수이식은 초진시 중증 재생불량성 빈혈 진단을 받은 환자 중에에서도 고위험군을 선정하여 시행하는 것이 바람직하다고 생각되며 중등도 이하의 재생불량성 빈혈에서는 면역조절요법(항림프구 혈청 치료)과 고식적치료가 우선적으로 권장되어야 할 것으로 사료된다. Background : It is well konwn that aplastic anemia is more prevalent in the Far East than elsewhere in the world. There have been many suggestions that the clinical features of the patients with aplastic anemia in Korea would be somewhat different from that of western countries. Analysis of clinical data of 32 cases of aplastic anemia diagnosed at Chungnam National University Hospital from August 1985 to July 1991 was done. Methods : Initially all patients were treated with oxymetholone (50-100mg/d) with or without prednisolone (5-10mg/d) and supportive care. The patients who did not respond to androgen therapy were treated with antilymphocyte globulin (ALG) (20mg/kg/d for 4 days) plus methylprednisolne (methyl PD) (20mg/kg/d for 5 days). Analysis of reponse to therapy was done in 31 patients who could be followed for more than 3 months. Results : 12 patients (37.5%) were in their third decade and 25 cases of patients (78.2%) were below 40 years of age. The incidence decreased in older age groups. Exposure to possible toxic agents were seen in 6 cases (18.8%) ; benzene was counted in 2 cases (6.3%), herb drug in 2 cases (6.3%), antifungal agent in 1 case (3.1%). One case of aplastic anemia occured after acute viral hepatitis infection (type B) (3.1%), Eleven (35.5%) out of thity-one patients responded to androgen therapy (CR : 16.1%, PR : 19.4%). Nine out of the twenty patients who did not respond to androgen therapy were treated with ALG plus methyl PD. Two patients (22.2%) out of 9 showed complete responses. Overall response of present series of patients was 42% (oxymetholone±prednisolone therapy : 35.5%, ALG+methyl PD : 22.2%). By Kaplan-Meier product limit estimation, median survival time of 31cases was 36 months and the actuarial survival at 72 months was 83.1%. The median survival time of 31 cases was 36 months and the actuarial survival at 72 months was 83.1%. The median survival time of severe aplastic anemia (32 months) was similiar with that of moderately severe aplastic anemia (37 months). Factors associated with favourable survival were male sex and presence of etiological factor (p<0.05). Conclusions : In the present series, the survival rate of patients with aplastic anemia were somewhat different from that of western countries. Since the prognosis of patients with aplastic anemia in Korea is more favourable. A randomized controlled study would be needed to define the therapeutic role of bone marrow transplantation in patients with severe aplastic anemia in Korea.