간세포암 환자에서 DNase , RNase 및 Rnase inhibitor 측정의 의의

계세협(Sea Hyub Kae),정유선(Yoo Sun Chung),장현주(Heon Ju Jang),정선화(Sun Wha Jung),김용태(Yong Tae Kim),강승식(Seung Sik Kang),이진(Jin Lee),곽상택(Sang Taek Kwak),주상언(Sang Aun Joo),유재영(Jae Young Yoo) 대한내과학회 1998 대한내과학회지 Vol.54 No.5

N/A Objective Activities of nucleases (acid DNase and neutral RNase) and RNase inhibitor 1mown to be involved in carcinogenesis and suppression of cancer were determined in cancer tissue, serum and ascitic fluid of patients with hepatocellular carcinoma and were compared with those of the controls. Also studied were nucleases and RNase inhibitor isolated from hepatocellular carcinoma tissue and ascitic fluid of the cancer patients to evaluate the properties and interactions between them. Method: Activities of nucleases and RNase inhibitor were measured in cancer tissue, serum and ascitic fluid of patients with hepatocellular carcinoma by ultraviolet spectrophotometry. Nucleases and RNase inhibitor were isolated from hepatocellular carcinoma tissue and ascitic fluid of the cancer patients by DEAE-cellulose column chromatography. As controls, normal tissue of the cancer patients, serum of healthy persons and ascitic fluid of cirrhotic patients were used. Result: Activities of DNase, RNase and RNase inhibitor were significantly increased in hepatocellular carcinoma tissue. DNase activity was not detected, RNase activity was increased and RNase inhibitor activity was unchanged in both serum and ascitic fluid of the hepatocellular carcinoma patients. DNase was isolated as a single enzyme and RNase as seven isozymes from the hepatocellular carcinoma tissue. The DNase isolated preferentially cleaved ds DNA over ss DNA and was endonuclease in nature (majority of hydrolytic products of DNA by the DNase were oligodeoxyribonucleotides). Of seven RNase isozymes isolated from the hepatocellular carcinoma tissue, isozyme I exhibited nonsecretory nature of RNase and other six isozymes secretory nature of the enzyme. Activity of RNase isozyme V was greatly increased and the activity of inhibitor complexed with the isozyme V was also increased. RNase in ascitic fluid of the cancer patient was separated into four isozymes, of which isozyme I exhibited mixed form of secretory and nonseretory nature and greatly increased in its activity. RNase isozyme V isolated in the hepatocellular carcinoma tissue was not detected in the ascitic fluid, Conclusion: The use of the nucleases and the inhibitor in the cancer tissue as biochemical markers for the hepatocellular carcinoma was suggested. RNase was released into the body fluid from the cancer tissue and could be used as a diagnostic marker for the hepatocellular carcinoma. An important rale of the DNase in carcinogenesis of the liver was suggested. RNase isozyme V was limited in the cancer tissue and RNase isozyme I and V and inhibitors associated with these isozymes might be involved in carcinogenesis processes, suppression of cancer and maintenance of tocellular carcinoma through their interactions.

간세포 암종에 특이한 Ribonuclease Isozyme의 작용기전과 저해에 관한 연구

오승상,이용성,고재경 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.2

Neutral ribonucleases(RNases) were isolated and purified in the central area and the peripheral area of hepatocellular carcinoma tissues by a DEAE-cellulose column chromatography and high performance liquid chromatography(HPLC). Of the RNase isozymes isolated, the RNase isozyme V presumed to be specific to the hepatocellular carcinoma was examined for substrate specificity and mechanism of action of the isozyme to investigate the role of the RNase isozyme in the processes involved in carcinogenesis and suppression of the hepatocellular carcinoma. Free RNase activity was significantly increased in the peripheral area of the hepatocellular carcinoma tissue, but decreased in the central area of the carcinoma tissue, RNase inhibitor activity expressed as latent RNase activity was also increased in the peripheral area, but unchanged in the central area of the carcinoma tissue, Free RNases in both central and peripheral area of the carcinoma tissue were separated into 7 isozymes, of which RNase isozyme V was activated in the peripheral area of the carcinoma tissue and RNase inhibitor activity complexed with the isozyme was also greater in the peripheral area, suggesting the RNase isozyme V might play as important role in carcinogenesis of the hepatocellular carcinoma. RNase isozyme V isolated from the hepatocellular carcinoma tissue was further separated and purified by a HLPC into two protein subpeaks, a distinct RNase activity(RNase isozyme V(12-14)) being observed between two protein subpeaks. The reason for observing higher RNase activity in the pruified isozyme from control lover tissue than in that from hepatocellular carcinoma tissue was unclear. The RNase isozyme V pruified by HPLC was much more active toward poly C than RNA as substrate, indicating the isozyme as secretory type RNase. RNA/poly C ratio of the pruified isozyme from the carcinoma tissue was observed to be somewhat different from that from the control liver tissue. The activity of the purified RNase isozyme V (12-14) measured using poly C as substrate was inhibited by a variety of polyribonucleotides and DNA, the degree of inhibition being different between the isozyme from the carcinoma and that from the control. Majority of products of poly C digest by the action of the purified RNase isozyme V (12-14) from the peripheral area of hepatocellular carcinoma was found to be oligoribonucleotides, indicating that the isozyme was an endoribonuclease in nature. The present study indicated that the RNase isozyme V pruified from the peripheral area of the hepatocellular carcinoma was the secretory type RNase specific to the heaptocellular carcinoma, the isozyme was inhibited by polyribonucleotides and DNA, and the isozyme was an endoribonuclease in nature, suggesting that the RNase isozyme V might play an important role in the process involved in suppression of hepatocellular carcinoma and that the process could be modified by RNase inhibitor or base sequence of RNA.

PIVKA - 2 ; 새로운 간세포암표지자로서의 의의

최성호(Seong Ho Choi),신영민(Young Min Shin),김상현(Sang Hyun Kim),박승근(Seung Keun Park),이헌직(Hun Jig Lee),강대환(Dae Han Kang),조몽(Mong Cho),양웅석(Ung Suk Yang),문한규(Han Gyu Moon) 대한내과학회 1993 대한내과학회지 Vol.45 No.1

N/A Background: AFP is known as one of the most sensitive tumor markers for hepatocellular carinoma. But in many cases of hepatocellular carcinoma, low or negative levels of AFP have been observed. And because AFP levels may be increased in cases of other liver diseases such as liver cirrhosis, its specificity and sensitivity are problems. PIVKA-II has been studied as a new tumor marker for hepatocellualr carcinoma with AFP. It is a precursor protein of prothrombin and is converted to active form of prothrombin by the action of Vitamin K dependent carboxylase in hepatocyte microsomes. As this process can be suppressed by Vitamin K deficiency or Vitamin K antogonist such as warfarin, PIVKA-II levels might be increased due to functional derangement of Vitamin K-dependent carboxylation in hepatocellular carcinoma. We measured the levels of PIVKA-II in patients with various liver diseases including hepatocellular carcinoma and evaluated the meaning of increased PIVKA-II levels. Methods: We measured the levels of PIVKA-II in the plasma of 30 patients with hepatocellular carcinoma and 41 patients with other liver diseases by EIA method using monoclonal antibody specific to PIVKA-II. AFP was checked by RIA method. Results: The levels of PIVKA-II were increased above 0.1 AU/mL in the plasma of 25 (83%) patients with hepatocellular carcinoma and 1 patient with liver cirrhosis and 1 chronic hepatitis, 1 receiving warfarin, 2 toxic hepatitis, 2 cholangiocarcinoma and 1 liver metastatis from stomach cancer. In this study, with diagnostic cut-off value of 0.1 AU/ mL, the sensitivity and specificity of PIVKA-II to detect hepatocellular carcinoma were 83.3% and 78% each. With cut-off value of 8.0 AU/ml, the sensitivity and specificity were 66.7% and 100% each. By the combination assay with the cut-off values of AFP above 100ng/mL & PIVKA-II above 0.1 AU/mL the sensitivity for hepatocellular carcinoma could be elevated to 86.7%. Conclusion: We can conclude that PIVKA-II is more sensitive and specific than AFP and is a useful tumor marker which can elevate the sensitivity and specificity to detect hepatocellular carcinoma by combination assay with AFP. And PIVKA-II can be a useful screening method to detect hepatocellular carcinoma arising from liver cirrhosis.

간세포암종에서 Cyclin D1과 pRb 발현에 대한 면역조직화학적 연구

최재호 외 중앙대학교 의과대학 의학연구소 2004 中央醫大誌 Vol.29 No.3·4

An alteration in the cell cycle-related genes is one of the most common events seen in human carcinogenesis. Although aberration of cyclin D1 and pRb have been reported to be involved in hepatocellular carcinoma, the stages of the multistep process of hepatocarcinogenesis affected by them remain unknown. So, to determine the role of cyclin D1 and pRb in hepatocarcinogenesis, I examined cyclin D1 and pRb expression immunohistochemically in hepatocellular carcinoma and non-cancerous tissue with cirrhosis and chronic hepatitis. The patient consisted of biopsied or surgically resected 40 cases of hepatocellular carcinoma with 12 cases of grade II and 28 cases of grade III, 10 cases of cirrhosis with or without hepatocellular carcinoma and 10 cases of chronic hepatitis. The results were as follows; 1. Cyclin D1 expression was observed in 25 of the 40 hepatocellular carcinoma (62.5%) and 3 of the 10 cirrhosis (30%). 2. Cyclin D1 expression of hepatocellular carcinoma was significantly associated with tumor differentiated grade (p=0.022) and T-stage (p=0.047); altered cyclin D1 expression occured in 6 of 12 (50%) and 19 of 28 (67.9%) grade II and grade III hepatocellular carcinoma; in 4/7 (57.1%), 6/9 (66.7%) and 8/11 (72.7%) stage II, stage III and stage IV. 3. pRb expression was observed in 3 of the 40 hepatocellular carcinoma (7.5%), and no expression was noted in cirrhosis and chronic hepatitis. Therefore, the results suggest that the cyclin D1 expression is closely associated with tumor progression and developing metastasis rather than that of pRb expression in cases of hepatocellular carcinoma.

원발성 간암에 있어서 종양표지자로서 이상 Prothrrombin ( PIVKA - 2 ) 측정의 유용성

이숭(Soong Lee),윤경환(Kyung Whan Yoon),구철(Chul Koo),최성규(Sung Kyu Choi),유종선(Jong Sun Rew),윤종만(Jong Mann Yoon) 대한내과학회 1990 대한내과학회지 Vol.39 No.1

N/A Abnormal prothrombin, known as PIVKA-II (protein induced by vitamin K absence or antagonist-II) or DCP (des-γ-carboxyprothrombin), is released from the liver into the blood of patients with vitamin K deficiency or vitamin K antagonist users (wafarin sodium), or patients with various liver diseases, especially hepatocellular carcinoma. Recently. abnormal prothrombin has been reported to be as good a marker of hepatocellular carcinoma as alpha-fetoprotein (AFP), and its production may be due to the reduction of vitamin K-dependent carboxylase activity. In order to assess the usefulness of abnormal prothrombin and the correlation between abnormal prothrombin and AFP in hepatocellular carcinoma, we measured the plasma abnormal prothrombin using enzyme immunoassay in 60 patients with liver diseases and in 15 healthy controls. The results were as follows: 1) The mean value of plasma abnormal prothrombin in the normal controls was 0,06±0.02 AU/ml. 2) The mean value of plasma abnormal prothrombin in patients with hepatocellular carcinoma was 5.82±4.78 AU/ml, and there were significant differences between hepatocellular carcinoma and liver cirrhosis, chronic hepatitis and other non-tumorous liver diseases. The positivity of abnormal prothrombin in hepatocellular carcinoma was 70.6% 3) The sensitivity and specificity of plasma abnormal prothrombin as a marker of hepatocellular carcinoma with a diagnostic cut-off value of 0.13 AU/ml were 70.6% and 90.7%, and they were 58.8%, and 97.7% with a cut-off value of 3.0 AU/ml, respectively. The sensitivity and specificity of AFP with a diagnostic cut-off value of 20 ng/ml werC 64.7% and 76.6% and they were 35.3% and 95.3% with a cut-off value of 400 ng/ml, respectively 4) 1 here was no significant correlation between the plasma abnormal prothrombin and serum AFP in patients with hepatocellular carcinoma (r=0.45 p>0. 05). 5) There was no significant correlation between the tumor size and plasma abnormal prothrombin (r=0.04, p>0.05) or the serum AFV level (r=0.01, p>0.05). These results suggest that plasma abnormal prothrombin could be employed as a useful tumor marker together with AFP in patients with hepatocellular carcinoma.

간경변증과 원발성 간암 환자의 혈중 동과 아연에 관한 연구

안기완(Gi Wan An),김만우(Man Woo Kim),조건국(Kun Kook Cho),조승렬(Seung Ryul Cho),김만중(Man Jung Kim),김원학(Won Hak Kim) 대한내과학회 1987 대한내과학회지 Vol.33 No.3

N/A The copper and zinc concentrations were measured in sera of 28 cases of liver cirrhosis, 10 cases of liver cirrhosis with hepatocellular carcinoma, 17 cases of hepatocellular carcinoma and 48 normal control cases by atomic absorption spectrometer in Chosun University Hospital from July 1985 to July 1986. The result were as follows; 1) The mean concentrations of copper in serum of normal control and liver cirrhosis group were 96.03±5. 02, 86.61±7.98 ㎍/dl respectively, but in serum of hepatocellular carcinom a with and without liver cirrhosis the concentrations were each 123.74±13.04 and 127.93± 24.24 ㎍/dl, which were significantly higher than that of normal control group (p<0.001). 2) The mean concentration of zinc in serum of normal control group was 104.81±3.40 ㎍/dl, but in serum of liver cirrhosis, hepatocellular carcinoma with and without liver cirrhosis the concentrations were each 69.03±10.55, 76.01±11.12 and 58.72±12.65 ㎍/dl, which were significantly lower than the former (p<0.001). 3) The ratio of copper to zinc level in serum of normal control group was 0.940.06, but in serum of liver cirrhosis, hepatocellular carcinoma with and without liver cirrhosis the concentration-ratios were each 1.36±0.05, 1.65±0.03 and 2.34±0.59, which were higher than the former. But in serum of hepatocellular carcinoma with and without liver cirrhosis, the ratios of copper to zinc level were significantly higher than that of liver cirrhosis (p < 0,001). Consequently, in hepatocellular carcinoma with and without liver cirrhosis group, the serum copper levels were significantly higher in comparison with that of normal control group. In hepatocellular carcinoma with and without liver cirrhosis group, the serum zinc levels were significantly lower in comparison with that of normal control group. In hepatocellular carcinoma with and without liver cirrhosis, the ratios of copper to zinc level were significantly highter than that of normal control group, These findings demonstrate the usefulness of these parameters as the diagnostic aid in patients with hepatocellular carcinoma.

Early Hepatocellular Carcinoma: Three-Phase Helical CT Features of 16 Patients

이종미,이원재,임효근,임재훈,최나미,박미현,김상원,박철근 대한영상의학회 2008 Korean Journal of Radiology Vol.9 No.4

Objective: To evaluate the three-phase helical CT features of early hepatocellular carcinomas, based on the new Japanese classification. Materials and Methods: Over the course of an eight-year period, we collected 16 pathologically proven early hepatocellular carcinomas from 16 patients having undergone a three-phase helical CT prior to surgery. The three-phase CT images were acquired at 20 35 sec (arterial phase), 70 sec (portal phase), and 180 sec (equilibrium phase) from the begining of intravenous injection of contrast material. All the CT images were retrospectively analyzed by two radiologists in consensus, based on their description of morphologic (size, margin, fibrous capsule and mosaic pattern) and enhancement patterns of tumors. Results: Only seven (44%) of the 16 early hepatocellular carcinomas having undergone a CT were described (mean diameter, 1.2 cm; range, 0.4 2.5 cm). All the tumors had an ill-defined margin with no fibrous capsule. The mosaic pattern was found in only one tumor. Only three (43%) of the seven tumors detected on CT were hyperattenuating during the arterial phase. The four remaining tumors (25%) were hypoattenuating throughout the three phases. Conclusion: Despite the higher resolution provided by the three phase scans, the contrast-enhanced CT provides only limited detection of the variable morphologic and enhancement features of early hepatocellular carcinomas. Objective: To evaluate the three-phase helical CT features of early hepatocellular carcinomas, based on the new Japanese classification. Materials and Methods: Over the course of an eight-year period, we collected 16 pathologically proven early hepatocellular carcinomas from 16 patients having undergone a three-phase helical CT prior to surgery. The three-phase CT images were acquired at 20 35 sec (arterial phase), 70 sec (portal phase), and 180 sec (equilibrium phase) from the begining of intravenous injection of contrast material. All the CT images were retrospectively analyzed by two radiologists in consensus, based on their description of morphologic (size, margin, fibrous capsule and mosaic pattern) and enhancement patterns of tumors. Results: Only seven (44%) of the 16 early hepatocellular carcinomas having undergone a CT were described (mean diameter, 1.2 cm; range, 0.4 2.5 cm). All the tumors had an ill-defined margin with no fibrous capsule. The mosaic pattern was found in only one tumor. Only three (43%) of the seven tumors detected on CT were hyperattenuating during the arterial phase. The four remaining tumors (25%) were hypoattenuating throughout the three phases. Conclusion: Despite the higher resolution provided by the three phase scans, the contrast-enhanced CT provides only limited detection of the variable morphologic and enhancement features of early hepatocellular carcinomas.

간외 전이로 처음 발견된 간세포암종 상완골의 단독전이로 내원한 간세포암종

박윤지 ( Yun Ji Park ),임평숙 ( Pyeong Suk Yim ),김인희 ( In Hee Kim ),김대곤 ( Dae Ghon Kim ) 대한간암학회 2010 대한간암학회지 Vol.10 No.-

Extrahepatic spread of hepatocellular carcinoma is uncommon. Also, initial clinical presentation that manifests as symptomatic metastasis is unusual. We experienced a case the bone tumor originated from hepatocellular carcinoma that was diagnosed and successfully treated in spite of lack of histological findings. A 76-year-old man presenting severe pain of left upper arm, came to our department of orthopedic surgery and was referred to our hepatology due to be presumed left arm bone tumor as the metastatic hepatocellular carcinoma. Magnetic resonance image and positron emission tomography revealed multinodular hepatocellular carcinoma and single metastatic tumor of left upper arm. A part of left upper arm suggested to metastatic bone tumor was removed by surgical resection and replaced to artificial bone cement. The final pathological result the bone tumor tissue obtained by surgical resection was assumed an extrahepatic metastasis from unknown origin carcinoma. It was difficult to prove whether the humerus metastatic bone tumor was originated from primary hepatocellular carcinoma obviously, in view of pathologic findings. However, we could not find out any other primary carcinoma except hepatocellular carcinoma, unavoidably diagnosed humerus metastatic tumor as extrahepatic bone metastasis originating from primary hepatocellular carcinoma.

간세포암환자에 있어서 이상프로트롬빈 ( PIVKA - 2 ) 의 진단적 의의

신영민(Young Min Shin),이선희(Sun Hee Lee),이동필(Dong Pil Lee),최성호(Seong Ho Choi),백태현(Tae Hyun Paik),최철수(Chul Soo Choi),송근암(Geun Am Song),조몽(Mong Cho),양웅석(Ung Suk Yang),문한규(Han Kyu Moon) 대한내과학회 1995 대한내과학회지 Vol.48 No.1

N/A Results: 1) The positivity of PIVKA-2 in hepatocellular carcinoma was 82.9% (34/41) and the mean value of plasma PIVKA-2 was 19.90±16.48 AU/ml, and there were statistically significant differences between the patients with hepatocellular carcinoma and control groups. 2) The positivity of AFP in hepatocellular carcinoma was 61% (25/41) and the mean value of serum AFP was 218.5±180.2ng/ml, and there was no statistically significant difference between the patients with hepatocellular carcinoma and those with liver cirrhosis. 3) The sensitivity and specificity of PIVKA-2 as a marker of hepatocellular carcinoma with cut-off value of 0.1 AU/ml were 82.9% and 87.2%, and those of AFP with cut-off value of 20ng/ml were 61.0% and 71.8% respectively. 4) By the combined assay with the cut-off values of AFP above 20ng/ml and PIVKA-2 above 0.1 AU/ml, the diagnostic sensitivity for HCC can be elevated to 92.7%. 5) There was no significant correlation between the plasma PIVKA-2 and serum AFP in patients with hepatocellular carcinoma. Conclusions: PIVKA-2 has higher sensitivity and specificity than AFP in patients with hepatocellular carcinoma which is larger than 2㎝ in diameter by imaging diagnosis and especially it is valuable tumor marker which can improve sensitivity and specificity to diagnose hepatocellular carcinoma by combination assay with AFP.

Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma

( Chai Hong Rim ) 대한간암학회 2021 대한간암학회지 Vol.21 No.2

There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines. (J Liver Cancer 2021;21:113-123)