소화기암 세포주에 대한 Interferon 의 항암제 세포독성 증강 효과

김성철(Sung Chul Kim),길준영(Jun Young Kil),전의건(Eui Gun Chun),윤환중(Hwan Jung Yun),조덕연(Deog Yeon Jo),김삼용(Sam Yong Kim),김영건(Young Kun Kim) 대한내과학회 1992 대한내과학회지 Vol.43 No.5

N/A Background: 1nterferons (IFN) have antiproliferative activity and immune moduiatory function. Interferons and cytotoxic drugs have different mechanism of action on cancer cells. To investigate the interaction of interferons with cytotoxic drugs, we treated human gastrointestinal cancer cells with combinations of anti- cancer drugs and interferons. Methods: Using the colorimetric [3-(4, 5-dimethlyth- iazo1-2-yl)-2, 5-diphenyltetraxolium bromide] (MTT) assay, we evaluated the chemosensitivity of anticancer drugs (5-fluorouracil, adriamycin), and the inhibitory effects of alpha interferon and gamma interferon, and the cytotoxic effects of the combination of interferons and anticancer drugs against the human gastric cancer cell line SNU-5 and the colon cancer cell line SNU-C. Results : Both 5-FU and adriamycin produced dosedependent inhibition of cancer cell growth; the alpha interferon and the gamma interferon had 12% and 18% inhibitory effects against SNU-5 cells respectively, and they showed 29% and 30% inhibitory effects against SNU-C1 cells respectively. Cytotoxicity of anticancer drugs was markedly augmented by the addition of alpha or gamma interferons. The II4 values of 5-FU and adriamycin decreased to 1/ 37 and 1/33, respectively, when alpha interferon was added to these drugs, and ID50 values of 5-FU and adriamycin decreased to 1/7 and 1/5.4, respectively, when the gamma interferon was added. Conclusions: The results indicate that interferons, when used concomitantly with the cytotoxic drug 5-FU or adriamycin, can augment the cytotoxicity of the latter drugs. A clinical trial incorporating interferons with anticancer drugs in gastrointestinal malignancies should be warranted.

구인두 캔디다증에 대한 Fluconazole의 치료효과

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

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.

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.

급성골수성백혈병 환자에서 DAV 병용화학요법 후의 장기생존율

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

Background : Despite substantial progress, the treatment of acute myeloid leukemia(AML) has produced complete remission in 60-80% of patients receiving induction chemotherapy, and median remission duration is about 12 months and only 20% to 35% of patients undergoing consolidation chemotherapy achieve long-term disease-free survival(DFS). We evaluated the long-term outcome of AML patients treated with doxorubicin/Ara-C/VP-16(DAV) induction chemotherapy and consolidation/intensification therapy. Method : Induction therapy : From January 1986 to December 1991, twenty three patients with previously untreated acute myelogenous leukemia received a course of 45mg/㎡ doxorubicin daily intravenously for three consecutive days with Ara-C at 100mg/㎡ by continuous intravenous infusion for eight consecutive days and VP-16 at 100mg/㎡ daily intravenously for three consecutive days. A second course of treatment was started if leukemia persisted on 22 days after treatment. Post-remission therapy : Three to six cycles were given at three or four months interval with Ara-C/doxorubicin/VP-16 regimen or other therapy. Results : Twenty two pateints were evaluable and complete remission was achieved in 16 of 22(73%). Median duration of complete remission was 8 months. The relapse rate was 81% and 63% relapsed in first year. 4-year survival rate of patients entering complete remission(n=16) was 19% and median survival duration was 14.5 months. The postremission chemotherapy was the only significant prognostic factor influencing long term disease free survival. No significant correlation was observed between the probability of survival and age (40< or >40), sex, FAR subgroup, and leukocyte count at diagnosis. The median survival duration were 21 months and 12.5 months for patients who received, or not received postremission chemotherapy respectively(P=0.035). Conclusion : Our results show that DAV combination chemotherapy is a useful therapeutic regimen in remission induction and postremission chemotherapy offering survival advantage in patients with AML entering complete remission.

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.

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

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