한국인 제1형 당뇨병에서 체도 세포질 항체의 양성률 : 항GAD항체, 항ICA512항체, 항phogrin항체의 조합 측정으로의 대체 가능성 Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies

김경아,김동준,정재훈,민용기,이문규,김광원,진동규,고경수,김상진,이명식 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:최근 당뇨병의 분류를 새로 제정함에 있어 자가항체가 양성이면 임상형에 상관없이 제1형 당뇨병으로 분류하자는 제안이 나옴으로써 자가항체의 중요성은 더욱 커질 것으로 예상된다. 특히 우리나라와 같이 비비만형인 제2형 당뇨병이 많은 나라에서는 당뇨병의 병인 규명에 자가항체가 중요한 위치를 차지할 것으로 사료된다. 자가항체 중에서 전통적으로 측정되어온 췌도 세포질 항체(ICA)는 표준화하기 어렵고 기술적으로 제한점이 많으며 현실적으로도 췌장 공여자가 적은 점 등이 문제로 알려져 있다. ICA의 대응 항원들로는 GAD(glutamic acid decarboxylase), IA­2(islet­associaated antigen­2;ICA512), IA­2β(phogrin)등이 있다. 이러한 대응 항원에 대한 특이적인 자가항체의 측정은 ICA에 비해 표준화되었으며 최근에는 방사면역측정법(radioimmunoassay;RIA)키드까지 등장하여 손쉽고 정확히 이를 측정할 수 있게 되었다. 연구자들은 한국인 제1형 당뇨병에서 측정법이 표준화 되어 있는 항GAD항체 및 항ICA512항체 조합(combimation)의 조합으로 ICA의 측정을 대신할 수 있는지를 조사하였고 더 나아가 항phogrin항체의 조합 측정으로 임상적 유용성이 있는지 보고자 하였다. 방법: ICA는 면역조직화학 염색법을 이용하였다. 항 GAD항체는 상업화 된 키드(RSR??, United Kingdom)를 이용하였다. 항 ICA512항체와 항phogrin항체의 측정은 in vitro transcription&translation한 후 이를 이용해 방사면역 침전법을 이용하였다. 대상 환자로는 전형적 제1형 당뇨병 76명, 지진형 제1형 당뇨병 22명, 제2형 당뇨병 39명이었으며 각 군간의 연령은 각각 22.8±14.0, 37.9±13.9, 45.3±12.3세였다. 결과:1)전형적인 제1형 당뇨병에서는 ICA의 양성률이 30%, RIA조합만의(항GAD항체 또는 항 ICA512항체 또는 항phgrin항체 한가지에라도 양성인 경우)양성률이 57%이었다. 지진형 제1형 당뇨병에서는 각각 18%, 50%이었다. 제2형 당뇨병에서는 각각 7.7%, 5.1%이었다. 2)각 군에서 ICA가 양성인 군에서 RIA조합 양성률을 보면 전형적 제1형 당뇨병에서는 96%, 지진형 제1형 당뇨병에서는 100%에서 양성이었고 제2형 당뇨병에서는 RIA 조합 양성이 없었다. 각 군에서 ICA가 음성인 군에서도 RIA 조합시 전형적 제1형 당뇨병에서는 40%, 지진형 제1형 당뇨병에서는 39%에서 양성이었고, 제2형 당뇨병에서는 5.6%에서 양성이었다. 3)전형적 제1형 당뇨병에서 ICA가 양성인 군(n=23)에서 96%가 RIA조합 양성이었는데 이때 각각의 RIA유형을 보면 항GAD항체 양성이 87%였다. 한편 항 ICA512항체 양성이 48%, 항phogrin항체 양성이 44%이고 항GAD항체 도는 항ICA512항체 양성이 96%를 차지한다. 지진형 제1형 당뇨병에서는 ICA가 양성인 군(n=4)에서는 항 GAD항체 양성이 3명, 항ICA512항체 양성이 1명이었다. 따라서 기존의 ICA를 RIA조합으로 대체할 수 있을 것으로 사료되었는데 이때 항GAD항체와 항ICA512항체의 조합이 도움이 되겠고 항phogrin항체의 추가적인 검사는 일부의 환자에서만 도움이 되리라 사료된다. 4)이환 기간에 따라 ICA와 RIA조합을 비교시 ICA는 차이가 없었으나 RIA조합의 양성률은 지진형 제1형 당뇨병에서 4년 이상의 이환 기간이 지나면 그 이전보다 떨어졌다. 5)발병 연령에 따라 ICA와 RIA조합을 비교시 ICA 양성률이 전형적 제1형 당뇨병에서 15세 이전에 발병한 그룹에서 그 이후에 발병한 그룹보다 유의하게 높았다. 결론:이상의 결과를 요약하면 항GAD항체 및 항ICA512항체 측정의 조합은 ICA보다 민감도가 높아 기존의 ICA를 대체함은 물론 임상적 이용에서 현격한 우월성을 보이며, 성인에서 발병한 비전형적인 당뇨병의 분류에도 도움이 될 것으로 사료되었다. 추가적인 항phogrin항체의 측정은 임상적 유용성이 없었다. Background : Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA 512 (ICA 512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA 512A has the power to detect a majority of ICA and 97 ~ 100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or for classifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1≥ of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. Methods : The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radiommunoassay kits utilizing the ^125I-labeled recombinant GAD65 (RSR®, United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin c DNA. Serum was obtained from 76 patients with type 1 diabetes(mean age 45.3± 12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0±4.6 and 10.1±9.5 years, respectively at the earliest serum sampling. Results: 1) In typicaltype 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typicaltype 1 diabetes. Among the 53 ICA-negative patients with typicaltype 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly pregressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA-negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% FOR ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age(65% vs 53%). Conclusion : Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset a typical diabetes(J Kor Diabetes Asso 25 :430~445, 2001).

두부 손상이 골절 칭 촉진 시동물 모델 및 유전자 발현 분석

김경희,김학선,문성환,김향,권언해,이환모,박희완,한수봉,문은수 대한정형외과연구학회 2003 대한정형외과연구학회지 Vol.6 No.2

Rifampicin에 의한 것으로 추정되는 위막성 대장염1예

김수현,이은우,정종혁,문승현,김동한,양혁승,오영상,김호동,김도현,박혁,박정환,박경옥,이영직 朝鮮大學校 附設 醫學硏究所 2006 The Medical Journal of Chosun University Vol.31 No.2

Pseudomembranous colitis, caused by altering the normal colonic flora and allowing the multiplication of Clostridium difficile, is an deleterious adverse effect of antibiotics. But it is rarely reported by rifampicin. Rifampicin is one of the first line drug in the treatment of tuberculosis and many patients are exposed to its potential adverse effects. We experienced a patient that had abdominal discomfort and hematochezia due to pseudomembranous colitis after receiving antituberculous medication, and which was probably caused by rifampicin. A 82 years old man was admitted with abdominal discomfort and hematochezia for one week. On the past history he had been diagnosed as endobronchial tuberculosis about 4 months ago. Colonoscopy revealed multiple discrete whitish mucosal lesion on rectosigmoid colon, and histologic findings were consistent with pseudomembranous colitis. The antituberculous agents were discontinued and vancomycin was administered. The patient's symptoms were resolved within several days. There was no recurrence after reinstitution of the antituberculous agents excluding rifampicin. We report here on a case of pseudomembranous colitis probably due to rifampicin.

당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

Kim's Femoral Stem의 임상적 고찰

김영민(Young Min Kim),김희중(Hee Joong Kim),진종수(Jong Soo Jin),문영완(Young Wan Moon) 대한정형외과학회 1991 대한정형외과학회지 Vol.26 No.5

수소공여제가 열경화성플라스틱의 열분해에 미치는 영향

김승문,김성수,김상국,정수현 한국공업화학회 2003 응용화학 Vol.7 No.1

이상의 실험 결과로부터 다음과 같이 요약할 수 있다. 1. 경유를 수소공여제로 사용하여 450℃에서 열분해 하였을때의 분해율은 49.70%으로 PP의 32.83%에 비해 분해율이 50% 향상되었다. 2. TS-D-450의 액상 수율이 40.63wt%로 가장 높았다. The effect of the Zeolite HX, NaX, and KX prepared by ion-exchange method, on the reduction-carburization of WO₃was studied, This study was performed at the temperature range from 300 ℃ to 725 ℃ with CO gas. The produced gas. CO₂, was analyzed by mass spectroscopy. The addition of the Zeolite HX, NaX, and KX into WO₃increased the efficiency of the reduction-carburization of WO₃and Zeoilte HX with the strongest acidity was the most effective on reduction-carburization among them. The Zeolite HX, NaX, and KX improved the oxygen mobility of WO₃and the acidity of the Zeolite was directly related to the increasing efficiency of reduction-carburization of WO₃.

황색포도알균에 의한 급성 화농성 천골장골관절염 1예

문수연,신준범,김경엽,김석연,문수영,문송미,이미숙 대한감염학회 2007 감염과 화학요법 Vol.39 No.5

저자들은 특별한 위험 인자 없이 심한 허리 및 왼쪽 둔부 통증으로 내원하여 황색포도알균에 의한 균혈증이 진단된 젊은 여성에서 드문 감염질환인 화농성 천골장골관절염과 엉덩근 및 엉덩허리근 농양이 발생된 예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Pyogenic sacroiliits is a rare disease and the diagnosis is difficult because of unawareness of the disease and nonspecific symptoms and signs mimicking septic hip, iliopsoas muscle abscess and herniation of intervertebral disk. There are some predisposing factors related to the disease like trauma, pregnancy, intravenous drug abuse and infection of other systems such as skin, genitourinary system and heart. Staphylococcus aureus is the most common causative bacteria. Here we describe a case of 27-year-old woman presented with acute onset of back and left buttock pain. Bone scintigraphy revealed increased uptake at left sacroiliac joint and computed tomography of the pelvis showed left sacroiliitis with left iliacus and iliopsoas abscess. There was no history of usual predisposing conditions. S. aureus was grown from blood cultures and the patient improved with 2 weeks of intravenous cefazolin followed by 4 weeks of oral clindamycin treatment.

Mirizzi 증후군의 변형된 분류와 치료

김형철,강길호,채만규,김성용,백무준,이문수,박상흠,이문호,김창호,송옥평,조무식,박희주 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

Purpose : The Mirizzi syndrome is relatively rare and preoperative diagnosis of this disease is difficult. In 1978, Morelli suggested the subclassification of the Mirizzi syndrome into acute or chronic form. We experienced 5 cases of acute form. We analysed clinical features, preoperative radiologic findings and operative findings of 18 cases including acute forms which were diagnosed as Mirizzi syndrome and should suggest the modified classification of Mirizzi syndrome for choice of appropriate treatment. Method : From January 1995 to December 1998, 18 cases, of which 8 cases were diagnosed at Soonchunhyang University Chunan Hospital, and 10 cases were reported in the Korean Journal were retrospectively analysed with regard to clinical features, preoperative radiologic findings and operative findings. According to the clinical features, whole cases were divided into type Ⅰ(acute form) and type Ⅱ(chronic form) and then each type of cases were subclassified according to preoperative radiologic findings and operative findings. Results : Of 18 cases there were 5 cases in type Ⅰ(27.8%), 13 cases in type Ⅱ(72.2%). Type Ⅱb was most common. Type Ⅰa cases were treated only with cholecystectomy. We applied cholecystectomy, T-tube choledochostomy and patch technique in type Ⅰb and thpe Ⅰc cases. Cholectystectomies including removal of gallstones and internal drainage procedures were done in type Ⅱ chronic forms. Conclusion : The acute form(Type Ⅰ) of Mirizzi syndrome was suggested by Morelli might be subclassified into typeⅠa,Ⅰb and Ⅰc following the presence of the necrotic defect in common hepatic duct. Through the modified classification of Mirizzi syndrome based on clinical feature, preoperative radiologic findings and operative findings, we can choice appropriate treatment.

이미지 데이터베이스를 위한 정보 검색 시스템의 설계 및 구현

김만순,오세봉,김미연,민은미,박미영,정문숙,문현수,김상욱 강원대학교 정보통신연구소 2002 정보통신논문지 Vol.6 No.-

This paper presents design and implementation of an information retrieval system for a large volue of an image database. Our system supports three kinds of queries: attribute-based queries, keyword-based queries, and color-based queries. The attribute-based query is the most-typical query that finds target images based on their attribute values. The keyword-based query is to find target images by referring to their description information their attribute values. Finally, the color-based query is to search for target images by comparing the colors of a query image with those of images in the database. In this paper, we presents the system architecture and approaches adopted in our system for supporting the above three queries effectively and efficiently. We also discuss the user interface of our system that enables users to manipulate our system easily and conveniently.

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.