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HBx형질전환 생쥐에서 발생한 간세포암종에서 H-ras 및 c-myc의 발현에 관한 연구
문형배,소병준,김학철,윤기중,한원철,조향정,유대열,정영진 圓光大學校 醫科學硏究所 2002 圓光醫科學 Vol.17 No.2
<연구목적> HBx형질전환 생쥐에서 발생한 간세포암종의 발암과정에 종양유전자(H-rgs, c-myc)의 발현 정도를 조사하고자 하였다. <연구방법> 정상생쥐 12마리(4-18개월) 및 HBx 형질전환 생쥐 44마리(4-18개월)를 대상으로 포르말린에 고정하고 파라핀에 포매한 간 조직을 이용하여 면역조직화학적염색을 실시하였다. 실험군은 정상 부위, 이형성 부위 및 종양 부위로 구분하였으며, 종양 부위는 소결절성병변 부위와 간세 포암종 부위로 구분하였고, 이형성병변 부위는 이형성병변만 발견되는 부위, 소결절성병변과 동반된 이형성병변 부위 및 간세포암종과 동반된 이형성병변 부위로 구분하였다. <연구결과> H-rgs의 발현은 정상 간조직에 비하여 이형성병변 부위(P<0.05) 및 종양 부위(P<0.01)에서 증가하였으며, 소결절성병변 부위과 간세포암종 부위 사이에서는 간세포암종 부위에서 증가된 경향이었으나 통계학적으로 유의한 차이가 없었으며, 각 이형성병변 부위 사이에서도 유의한 차이는 없었다. c-myc의 발현은 정상 간조직 및 이형성병변 부위에 비해 종양 부위에서 증가하였으며(P<0.001), 소결절성병변 부위와 간세포암종 부위에서는 비슷하였고, 각 이형성병변부위 사이에서도 비슷하였다. <결론> HBx형질전환 생쥐에서 발생하는 간세포암종의 발생에 H-rgs는 이형성 변화를 일으키는 시기에 관여하며, c-myc은 이형성병변에서 암으로 이행하는 시기에 관여할 것으로 생각한다. Background: This experiment was designed for the expression of H-ras and c-myc in hepatocarcinogenesis of the HBx transgenic mice. Methods: Immunohistochemical stains in the paraffin embedded tissue of the liver were used for the detection of H-ras and c-myc in the 12 normal mice and 44 HBx transgenic mice of the 4-18 month old. Results: Expression of the H-ras was significantly increased in the dysplastic area (P<0.05) and tumor area (P<0.01) than in the normal liver. But there were no differences of H-ras expression between areas of microscopically identified hepatocellular carcinoma (MI-HCC) and grossly identified hepatocellular carcinoma (GI-HCC) and dysplastic areas among the only dysplastic areas, dysplastic areas with MI-HCC and GI-HCC. Expression of the c-myc was significantly increased in the tumor area (P<0.001) than in the normal liver and dysplastic area. But there were no differences of c-myc expression between areas of MI-HCC and GI-HCC, and dysplastic areas among only dysplastic areas, dysplastic areas with MI-HCC and GI-HCC. Conclusions: Our study suggests that H-ras is related to the dysplastic change and c-myc is related to the neoplastic change in the hepatocarcinogenesis of the HBx transgenic mice.
결핵성 육아종에서 Thioredoxin peroxidase-2 의 발현
박근호,유형륜,정영진,윤기중,한원철,유대열,문형배 圓光大學校 醫科學硏究所 1999 圓光醫科學 Vol.15 No.2
Background: Thioredoxin peroxidase(TPX) is a kind of recently discovered antioxidant enzyme which react as rapid hydrogen ion donor for the removal of hydroperoxide. The action and distribution of the TPX was poorly understood in the human diseases. This experiments were designed for the study about the distribution of the TPX in the chronic granulomatous inflammation and about the correlation between the expression of TPX and the site of inflammation, histological activities of tuberculous inflammation or existence of mycobacterium in the inflammatory foci. Methods: The immunohistochemical stains were performed for the localization of the TPX-2 in the epithelioid cells, giant cells and lymphocytes in the chronic granulomatous inflammation. The tissue sections were obtained from the paraffin blocks of the 54 cases of tuberculosis (lung 21 cases, lymph node 12 cases, bone and soft tissue 12 cases, kidney 9 cases; active 33 cases, inactive 21 cases by the histologic classification; presence of mycobacterium 15 cases, no mycobacterium 39 cases by PCR reaction). Results: The expression of TPX-2 was 16.7% in the giant cells, 27.8% in the epithelioid cells and 100% in the lymphocytes of tuberculous inflammations. The expression of TPX-2 in the giant cells and epithelioid cells of the tuberculosis were 28.6% and 57.1% of the pulmonary tuberculosis; 33.3% in each cells of the renal tuberculosis; 0% in each cells of the lymph node or bone and soft tissue tuberculosis. The expression of TPX-2 in the giant cells and epithelioid cells were 9.1% in each cells of the active tuberculosis and were 28.6% and 57.1% in each cells of the inactive tuberculosis by histologic classification. The expression of TPX-2 in the giant cells and epithelioid cells was 40% in each cells of tuberculosis which mycobacteria were detected and the expression of TPX-2 was 7.7% and 23.1% in each cells which mycobacteria were not detected by PCR reaction in the paraffin embedded tissue. Conclusions: The above results were summarized that the TPX-2 in the giant cells and epithelioid cells were more frequently expressed in the inactive tuberculosis than in the active tuberculosis. These results suggest that the TPX-2 is a kind of regulating or suppressing factors in the activity of the tuberculosis.
Incidence of Hepatocellular Carcinoma in the Transgenic Mice Expressing HBx
Yu, Dae-Yeul,Han, Yong-Mahn,Jeong, Sangiyun,Murakami, Seishi,Moon, Hyung-Bae,Lee, Kyung-Kwang 가톨릭 의과학연구원 1997 가톨릭 의과학연구원 국제학술대회 Vol.1 No.-
HBV X gene has been suspected to play a positive role in hepatocarcinogenesis although the oncogenic mechanism of HBx remains obscure. HBx transactivates not only viral but also host genes related to cell proliferation and acute inflammatory response by modulating trascription directly or indirectly (Cheong et al., 1995 ; Haviv et al., 1995 and 1996 : Doria et al., 1995). Transactivation of genes including c-jun and c-myc may provide growth advantage to HBV-infected cells, raising probability of carcinogenesis (Alfiero et al., 1990 ; Twu et al., 1989). Recently another target of HBx has been proposed by the finding of the direct interaction of tumor suppressor p53 and HBx (Feitelson et al., 1993 : Wang et al., 1994 and 1995).
Studies on Aging Using Oxidative Stress Mouse Models
Dae-Yeul Yu(유대열) 한국실험동물학회 2010 한국실험동물학회 학술발표대회 논문집 Vol.2010 No.2
Aging is a multifactorial phenomenon characterized by a time-dependent decline in physiological function. The process of aging is one of the most complex and intriguing biological phenomenons. Through the years, hundreds (and perhaps more) of hypotheses have been proposed as potential reasons organisms age. One of the most studied and accepted hypotheses for the molecular basis of aging has been the oxidative stress theory of aging, which was first conceptualized by Denham Harman as the free radical theory of aging and has been modified to the Oxidative Stress Theory of Aging. The basis of this theory is that a chronic state of oxidative stress exists in all cells of aerobic organisms even under normal physiological conditions because of an imbalance between pro-oxidants and antioxidants, suggesting that antioxidants play an important role in protection of aging in mammalian cells. Several groups have genetically altered various components of the antioxidant defense system in mice to study the Oxidative Stress Theory of Aging. We already generated peroxiredoxin (Prx) Ⅰ and Ⅱ knockout mice to understand the roles of their proteins in vivo and are studying the mice to know whether Prxs are involved in protection of cellular senescence and organism aging. Underlying research results indicate that Prx Ⅰ and Ⅱ play a role in protection of cellular senescence in mice. In this symposium, I would like to introduce the results of transgenic/ knockout mice for antioxidant enzymes.
유대열 한국유가공기술과학회 1997 Journal of Dairy Science and Biotechnology (JMSB) Vol.15 No.2
Lactoferrin is an 80 kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two globular lobes and is relatively resistant to proteolysis. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Beside this, the functions proposed for lactoferrin are diverse and include immunomodulatory activity, regulation of myelopoiesis, cell growth promotion and differentiation, and antioxidant effects. Therefore lactoferrin has been a good target for commercial production. Until now lactoferrin has been purified from human, bovine, sheep, goat and horse milk. Complete amino acid sequences of the lactoferrin from human, murine, bovine, porcine, and caprine have been determined, either directly at the protein level or deduced from the nucleotide sequence and shown to display a high level of similarity. We, researchers in my laboratory, have been studied lactoferrin for mass production by using the techniques of transgenic animal, transgenic plant and microorganism. Here we present the data on structure, function and production of lactoferrin.