All - trans Retinoic Acid 가 급성전골수성백혈병의 관해유도와 혈액응고장애에 미치는 효과

김성권(Sung Gwon Kim),한치화(Chi Wha Han),김유진(Yoo Jin Kim),김동욱(Dong Wook Kim),진종률(Jong Youl Jin),민우성(Woo Sung Min),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.2

Objectives: APL, which characteristically shows t(15:17), accompanies fatal coagulopathy during remission induction with systemic chemotherapy alone. ATRA, a derivative of vitamin A, can differentiate APL cells as well as HL-60 cells in vitro and induce higher rate of complete remission(CR). Hence, we assessed the effect of ATRA on remission induction and coagulopathy in APL patients. Methods: (1) 42 patients diagnosed histologically in St. mary's hospital from June 1991 to June 1994 were included. (2) We compared the CR rate, the time required for restoration of derranged coagulation profiles, and the amount of coagulation factors including platelets among the chemotherapy group (control) and ATRA group. Results: 1) There was no difference in CR rate between the control group and ATRA group [84.2%(16 out of 19) vs 87.0%(20 out of 23), p>0.05)] and also no difference between two subgroups of ATRA [ATRA with chemotherapy; 83.3%(10 out of 12) vs ATRA without chemotherapy; 90.9%(10 out of 11), p>0.05] 2) In the ATRA group, the CR rate of newly diagnosed patients was 82.4%(14 out of 17). The first relapsed patients (4) and the second (2) were all achieved CR. 3) The mean duration of coagulopathy, time to normalization of PT, aPTT, FDP, fibrinogen level, was 12.0±10.4, 11.1±10.2, 16.5±9.3, 15.4±10.2 days after chemotherapy alone and 4.5±4.4, 3.7±3.7, 8.9±6.1, 8.1±6.5 days in the ATRA group(p<0.05). The amount of fresh frozen plasma used in the ATRA group for the purpose of correction of coagulopathy were significantly lower than the control group(p<0.05). The incidence of profound coagulopathy during the remission induction treatment in the ATRA group was significantly lower than the control group[40% (8 out of 20) vs 96.7%(13 out of 15), p<D.05]. And the amount of platelet transfusion was not different between two groups. 4) During the treatment with ATRA, four patients showed leukocytosis, but no patient developed typical retinoic acid syndrome. Other toxicities attributable to ATRA were headache in one case, increase in transaminase in one case, bone pain in one case. These side effects were mostly short-term and easily controlled by appropriate symptomatic therapy. Conclusion: (1) ATRA is relatively safe drug for inducing CR in patients with APL who are diagnosed freshly and even in relapse. (2) Also it is effective for reducing the severity of coagulopathy associated with APL itself.

50대 남자 환자에서 대세포 폐암으로 오인된 원발성 종격동 융모막암

김영신 ( Young Shin Kim ),한치화 ( Chi Wha Han ),정윤화 ( Yun Hwa Jung ),정민영 ( Min Young Jeong ),고성우 ( Seong Woo Go ),윤경진 ( Kyung Jin Yun ),정한희 ( Han Hee Chung ) 대한내과학회 2014 대한내과학회지 Vol.86 No.5

Primary mediastinal choriocarcinoma is an extremely rare extragonadal germ cell malignancy. A 58-year-old male presented with a lung mass, which was incidentally discovered during a periodic medical checkup. Percutaneous needle biopsy showed poorly differentiated carcinoma with large pleomorphic morphology. After the patient underwent right upper lobectomy and lymphadenectomy, the final diagnosis was choriocarcinoma. The patient received four sequential cycles of BEP chemotherapy (bleomycin, etoposide, cisplatin). After completion of BEP chemotherapy, follow-up positron emission tomography (PET) showed a complete metabolic response. Although the mediastinum is one of the most common primary sites of extragonadal germ cell tumors, primary mediastinal choriocarcinoma is liable to be misdiagnosed as lung cancer or Hodgkin lymphoma. Notably, large cell carcinoma of the lung can be confused with choriocarcinoma even after percutaneous needle biopsy. We report a case of primary mediastinal choriocarcinoma mimicking large cell carcinoma of the lung in a male patient in his 50s. (Korean J Med 2014;86:641-646)

녹색 형광단백 유전자를 함유한 아데노바이러스 주입시 마우스 생체내 발현양상

진종률(Jong Youl Jin),송치원(Chi Won Song),김진아(Jea Na Kim),이희진(Hee Jin Lee),김태규(Tai Gyu Kim),한치화(Chi Wha Han),엄현석(Hyun Seok Eom),박수정(Soo Jeong Park),정대철(Dae Chul Jeong),정낙균(Nak Gyun Chung),김소연(Soh Yeon Kim) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

Background : The green fluorescent protein (GFP) from jelly fish, A equorea victoria, has become a versatile reporter for monitoring gene expression in a variety of cells and organisms . Using GFP as a marker protein we studied whether there are any differencies in the expression patterns among organs in mouse after intravenous injection of adenovirus vectors with GFP gene. Methods : Recombinant E1, E3- defective type 5 adenovirus vectors (2×10(8)/mouse) with CMV promoter and GFP gene were injected into mice via tail vein. On 3, 6, 9, 14, 21, 28 days after gene transfer, 5 mice per experiment s were sacrificed by cervical dislocation and obtained liver , lung, heart , kidney, spleen, small intestine and bone. Half of them were examined by optical microscope after H-E stain. Another half were examined by fluorescent microscope after frozen section. Western blotting were done for each samples with anti- GFP monoclonal antibody and obtained GFP bands were quantitatively compared using Gel-Doc (Bio- Rad, USA) image analyzer. Results : In all organs that we obtained, expression of GFPs are noticed 3 days after gene transfer and reached a maximum around 9th to 14th days, after then the intensities are slightly decreased but maintained until 28th days as determined by Western blotting. On fluorescent microscopic examination, GFPs are well and most frequently expressed on lung among all the examined organs. There are little expression of GFPs on liver parenchymal area around the sinusoids and central veins, although patchy expression of GFPs are observed along the liver capsules. GFPs are highly expressed around the splenic trabecula area but splenic pulp area, it is very spar sely expressed. GFPs are more frequently and highly expressed around the renal tubular area than gromerular area in kidneys. In small intestine, GFPs are expressed on mid portion of microvilli. GFPs are not expressed on myocardium except scanty expression on endocardium. Bone marrow showed GFPs but precise localization is difficult because bony spicules mashed bone marrow during the preparation of frozen section. No specific pathologic lesions possibly related with adenovirus administration are observed on microscopic examination of H-E stained specimens. Conclusions: GFPs can be detected in cells without the fixing and staining and a good marker to studying the kinetics and persistence of adenovirus mediated gene therapy. And there are different GFP expression patterns according to the organs after intravenous injection of adenovirus vectors with GFP gene in mouse.(Korean J Med 61:537- 545, 2001)

림프종 환자에서 리툭시맙 치료 후에 발생한 저감마글로불린혈증

노현진 ( Hyun Jin Noh ),공봉한 ( Bong Han Gong ),김영신 ( Young Sin Kim ),정윤화 ( Yun Hwa Jung ),우인숙 ( In Sook Woo ),한치화 ( Chi Wha Han ) 대한내과학회 2014 대한내과학회지 Vol.87 No.3

Rituximab, an anti-CD20 monoclonal antibody, is an effective target agent against the B lymphocytes in B-cell lymphoid malignancies and various lymphoproliferative diseases. Moreover, the toxicity of rituximab is less severe than that of conventional cytotoxic agents, which has promoted the widespread application of rituximab in the treatment of B-cell lymphoma. However, depletion of B lymphocytes by rituximab, which leads to secondary hypogammaglobulinemia, can cause deterioration of humoral immunity. Although immune reconstitution after hematopoietic stem cell transplantation is known to prevent prolonged hypogammaglobulinemia, very few cases of long-standing hypogammaglobulinemia have been reported. We report herein a case of prolonged hypogammaglobulinemia after rituximab-containing chemotherapy and splenectomy in a patient with non-Hodgkin`s lymphoma and discuss the clinical significance and pathogenetic mechanism of this phenomenon with a literature review. (Korean J Med 2014;87:357-362)

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

저골수 충실성 급성 골수성 백혈병의 치료방침 화학 요법과 골수이식

김영균(Young Kyoon Kim),노진탁(Jin Tark Nho),박은영(Eun Young Park),한치화(Chi Wha Han),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim),한경자(Kyung Ja Han),김원일(Won Il Kim) 대한내과학회 1988 대한내과학회지 Vol.35 No.6

N/A There have been a few repots of acute myelogenous leukemia (AML) presenting hypocellular bone marrow. Most physicians are reluctant to give these patients intensive chemotherapy because of the potential risk of serious bone marrow failure. We experienced 10 patients with hypocellular AML (HAML) that could be difined by the criteria of 30% or more atypical blasts and 50% or less cellularity in the bone marrow. There were six men and four women and their ages ranged from 20 to 67 years. Various regimens including low dose ara-C alone (4 cases) and low dose ara-C with modified TAD (1case), with mitoxanthrone (1 case) or with mithramycin (1 case) were applied. Of the remaming three patlents; one received supportive care only, another mithramycin alone and the third allogeneic bone marrow transplantation. As a result, the three cases who received either allogeneic bone marrow transplantation or low dose ara-C with modified TAD or that with mitoxanthrone entered into complete remission. However, only the patient who received allogeneic bone marrow transplantation is still alive. The duration of survival ranged from 2 months to 18 months; the median was 8 months. One of the most common complications during chemotherapy was severe bone marrow suppression and the major cause of death was various severe infections during the pancytopenic period. Though the most favorable therapy for HAML is still controversial, bone marrow transplantation is considered to be the choice of treatment at the present time for young patients with HLA-identical donors. If bone marrow transplantation is not available, a more aggressive form of therapy in addition to low dose ara-C will be preferable.

BH - AC ( N4 - Behenoyl - 1 - β - D Arbinofuranosylcytosine ) 가 포함된 복합화학요법에 의한 급성 골수성 백혈병의 관해유도

이종욱(Jong Wook Lee),최성호(Seung Ho Choi),진종률(Jong Youl Jin),한치화(Chi Wha Han),민우성(Woo Sung Min),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim) 대한내과학회 1990 대한내과학회지 Vol.39 No.5

N/A During the last decade, there has been substantial progress in the treatment of acute myelogenaus leukemia (AML) due to the advent of multi-drug combination chemotherapy and bone marrow transplantation. N4-Behenoyl-l-β-D arabinofuranosylcytosine (BHAC) is one of the Ara-C derivatives which has been found to possess strong antitumor activity regardless of administration schedules mainly because of its resistance to cytidine deaminase. Twenty-five previously untreated adult patients with AML (Group 1) and 10 relapsed or refractory patients with AML (Group 2) were treated with BHAC containing regimens for remission induction. Thirteen patients (52%) achieved complete remission (CR) in Group 1 and 3 patients (30%) in Group 2. The median durtion of CR was 6 months (4-22). All patients whose bone marrow on the 7th day of treatment course contained no blast cell (M0) or who were below 5% blast cells (M1) entered into CR, whereas those above 25% blast cells (M3) did not enter into CR. During induction chemotherapy, 3 patients died of sepsis due to perianal abscess (1) and CVA (1) in Group 1, and of acute fulminant hepatitis (1) in Group 2 before recovery of pancytopenia. Major toxicities and side effects were as follows: infection 31/32 (96.9%), nausa and vomiting 10/32 (31. 3%), stomatitis and oral ulcer 8/32 (25%), abnormal liver function test 4/32 (12,5%), and diarrhea 3/32 (9, 4%). Rut these could be circumvented by appropriate supportive care. Even if the duration of observation doesn`t seem to be enough to compare the remission rate of BHAC-containing regimens with that of other conventional inductive regimens, this study suggests that BHAC is as effective as Ara-C for remission induction of AML. Since we expect that the higher CR rate could be obtained by escalating the dose of BHAC, further clinical trials including multicenter studies are necessary to raise the CR rate.

피부 백혈병의 임상적 고찰

장인강 ( In Gang Jang ),이동원 ( Dong Won Lee ),한치화 ( Chi Wha Han ),김춘추 ( Chun Chu Kim ),조백기 ( Baik Kee Cho ) 대한피부과학회 1996 대한피부과학회지 Vol.34 No.4

Background: Leukemia cutis is readily recognized and documented by biopsy, in contrast. to leukemic involvement in more occult sites. Nine cases of leukemia cutis have been reported in the Korean literatures. However no collective clinical studies have been reported in Korea. Objective : We evaluated the differences in patient age and sex, the clinical appearences and distributions of the skin lesions, interval between diagnosis of systemic leukemia and skin involvement, clinical course, and prognosis according to the type of leukemias. Methods : We carried out a retvospective study of 22 cases of leukemia cutis. Clinical information was obtained from the records of of 22 patients diagnosed at St. Mary's Hospital from 1988 to 1995. All the included cases were well evaluated for their clinical and histopathologic findings. Results : 1. Among 22 patients with leukemia cutis, male patients outnumbered female by 2 to 1 and the mean age was 25.8 years. 2. The clinical appearance of leukemia cutis includes papules, macules, nodules, plaques in all types of leukemia. Ulcerative lesions and vesicles were seen infrequently in leukemia cutis. Leukemia cutis often involved saultiple location of the skin, with no specific predilection of the site. There were no differences in distribution of lesions depending on the types of systemic leukemia. 3. In 68% of the patients with leukemia cutis, the skin lesions developed after the systemic leukemia was diagnosed, and 14% of patients had concomitant, involvement. 18% of patients had skin lesions preceding the diagnosis of systemic leukemia, howevere cytochemical and cytomorphologic studies of bone marrow and peripheral blood smear were not employed at the time of the skin biopsy. 4. Fourteen of 22 patients(64%) did not achieve a complete remission following the diagnosis of leukemia cutis and two of 14 patients without having complete remission could achieve complete remissions with proper anticancer therapy after the diagnosis of leukemia cutis. Total eight patients(36%) achieved a complete remission, then they had a relapse of leukemia in the skin, without having had any skin involvement at the time of the diagnosis of leukemia. 5. Seventeen of 22 patients(77% ) who were being followed up in our series died after leukemia cutis was diagnosed. The mean intervals between diagnosis of leukemia cutis and death was 3.8 months and they died mostly within 1 year. Conclusion : The presence of leukemic infiltration in the skin may help the clinician suspect the early diagnosis and relapse of systemic leukemia. It appears that leukemia cutis is associated with a grave prognosis. (Kor J Dermatol 1996;34(4): 507-514)

몇가지 관해유도요법제에 의한 급성임파구성 백혈병의 관해율

강진형(Jin Hyoung Kang),진종률(Jong Youl Jin),홍영선(Young Seon Hong),한치화(Chi Wha Han),박종원(Jong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim),김학기(Hack Ki Kim) 대한내과학회 1987 대한내과학회지 Vol.32 No.5

N/A The case analysis of 74 patients, who were admitted to St. Mary's hospital from Jan, 1982 to Dec. 1986, and had a diagnosis as acute lymphocytic leukemia by bone marrow aspiration and biopsy was conducted. Of all the patients, the number of patients who were treated with VP regimens were 7, VPM regimens 6, VP, L-asp. regimens 4, L2, regimens 28, Modified L, regimens 15, miscellaneous regimens 3 for induction of complete remission. All of them were 63. We could find several interesting informations about the CR rate, duration of CR, survival rate between several prognostic factors. The CR rate in VP regimens was 42.9%, VP. L-asp. regimens 60.7%, L, regimens 67.9%, Modified L, regimen 93.3% According to the FAB classification, there were no difference in CR rate. (L1 76.2%, L2 70.3%, L3 80%) In patients who had CHOP regimen as consolidation, median, duration of CR was longer (6.6 months) than that in patients without CHOP (3.8 months). In the comparison of duration of survival between the immunologic classification, median duration of survival in C-ALL was 12 months and T-ALL was 4.5 months. We might come to conclusion as follows; 1) Modified L2 regimen is superior to other regimens to bring CR. 2) Early consolidation therapy give us more longterm disease free survival. 3) The survival rate of C-ALL is better than that of T-ALL.

국소진행성 췌장암 환자에서 종격동 림프절 전이로 오인된 종격동 방선균증

허정원 ( Jung Won Heo ),정한나 ( Hanna Joung ),우인숙 ( In Sook Woo ),한치화 ( Chi Wha Han ),정윤화 ( Yun Hwa Jung ) 대한내과학회 2017 대한내과학회지 Vol.92 No.3

Actinomycosis is a rare chronic suppurative infectious disease caused by Actinomyces spp. Actinomyces are anaerobic Gram-positive bacteria that colonize the mouth, digestive tract, and genital tract. Thoracic actinomycosis is caused by the aspiration of oropharyngeal materials or the spread of cervicofacial infections. Therefore, poor oral hygiene, smoking, and immunodeficiency are risk factors. Actinomycoses are frequently misdiagnosed as anatomical malignancies and thus assessments of the diseases underlying malignancies are often complicated by the presence of actinomycoses. Here, we report a case of mediastinal actinomycosis presenting with clinical and radiological features of metastatic pancreatic cancer. Clinicians should consider the presence of actinomycosis when cancer patients fail to respond to anti-cancer treatments. (Korean J Med 2017;92:303-307)