未成熟 흰쥐子宮의 Estrogen 受容體의 細胞內 分布 및 Progesterone 受容體에 對한 Tamoxifen의 作用

朴朗韻,鄭泰浩,曺準承 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.3

Estrogen의 작용은 세포내의 특이수용체와의 결합을 통해 특정유전자의 발현을 유도함으로써 이뤄진다는 정도로 밝혀져 있을 뿐 그 자세한 기전에 대해서는 잘 이해가 되지 않고 있어 estrogen 및 항estrogen의 표적조직내 존재여하에 따른 estrogen수용체의 세포내 분포에 대해서 알아보고자 하였다. 미성숙 흰쥐에 100㎍의 tamoxifen을 일회 투여하고 2, 6, 12, 24, 48, 72시간이 지난 후에 자궁에서 나타나는 변화를 살폈다. 자궁무게와 자궁내 DNA함량, 그리고 progesterone수용체의 함량은 tamoxifen투여후 시간이 지남에 따라 모두 증가되었다. Tamoxifen을 투여하지 않은 대조군에서의 estrogen수용체 핵과 세포질에 각각 50%씩 분포하였고 tamoxifen투여후에는 세포질내수용체가 점차 감소하고 핵내수용체는 증가되는 경향을 보였다. 또한 대조군에서는 거의 모든 수용체가 유리형으로 존재하였던데 반해 tamoxifen의 투여로 결합형 수용체의 증가와 함께 유리형의 감소가 초래되었다. 이상의 결과로써 미성숙 흰쥐 자궁세포내에는 핵과 세포질 모두에 유리형 수용체가 존재하며, tamoxifen은 이들 양 분획의 수용체에 모두 결합하고 세포질내에서 핵내로 수용체의 전이를 유발하며 동시에 새로운 수용체의 합성도 유도하는 것으로 사료된다. Although it is widely accepted that specific intracellular receptor proteins are involved in the estrogenic regulation of gene expression and growth in reproductive tissues, the precise nature of the regulation is poorly understood. Among the unresolved issues are the distribution and dynamics of the estrogen receptor protein in target tissues in the presence and absence of estrogens and antiestrogens. In this study, the effect of antiestrogen, tamoxifen, on subcellular distribution of estrogen receptor in immature rat uterus was determined. A single dose of tamoxifen(100㎍/rat) increased uterine wet weight, DNA content, and cytoplasmic progesterone receptor content 2, 6, 12, 24, 48, 72 hours after injection. Total estrogen receptor content progressively increased, peaked 48hr post-injection, while cytoplasmic receptor content decreased. In control uteri, nuclear estrogen receptors were almost unoccupied, but occupied receptors increased afrter tamoxifen treatment. The amount of unoccupied cytoplasmic receptors rapidly decreased 2hr postinjection and then gradually restored to that of control which was 74% of cytoplasmic receptors. These results suggest that in immature rat uterus both cytoplasm and nucleus contain unoccupied, free estrogen receptors and also suggest that tamoxifen can bind both cytoplasmic and nuclear 'estrogen receptros, increase total estrogen receptor content, and elicit some estrogenic effect.

복수내 Fibronectin, Adenosine Deaminase, Sialic Acid 및 지질의 감별진단적 의의

여승엽,박낭운,조준승 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.3

복수를 일으키는 질환의 감별진단에 사용하기 위하여, 복수액에서 몇가지 생화학적 지표를 측정하고, 각 지표들의 감별진단적 의의를 검정하여 보았다. 총 39명의 환자로부터 복수액을 채취하였는데, 그 중 16명이 악성종양, 5명이 결핵 그리고 18명이 간경변증 환자였다. Fibronectin과 sialic acid치는, 악성종양성 및 결핵성복수에서 간경변성복수에 비해 각각 유의한(p<0.01) 차이를 나타내었으나, 악성종양과 결핵 사이에서는 유의한 차이를 보이지 않았다. Adenosine deaminase치는 악성종양성, 결핵성 및 간경변성복수 모두에서 서로간에 유의한(p<0.01) 차이를 나타내었다. 또한 복수내 백혈구수, 단백질농도, 포도당농도, lactate dehydrogenase, 지질농도등 기존 생화학적 지표들이 측정치의 분포에 있어 이들 세군 사이에 상당한 중복을 나타낸 반면에 fibronectin, sialic acid, 그리고 adenosine deaminase측정치의 분포는 각각 세군 사이에 명확한 차이를 보여주었다. 이상의 결과로 미루어보아 복수액에서 fibronectin, sialic acid 및 adenosine deaminase를 측정함으로써 원인질환의 감별진단이 더욱 용이하고 정확하게 되리라 사료된다. Trying to find accurate markers to differentiate ascites, several biochemical parameters were measured in ascitic fluids. Ascitic fluid samples from 16 patients with maligancy, 5 patients with tuberculosis and 18 patients with liver cirrhosis were investigated. The levels of fibronectin and sialic acid were significantly higher in malignant and tuberculous ascites than cirrhotic ascites(p<0.01) but showed no significant difference between malignant and tuberculous ascites. The activities of adenosine deaminase in malignant, tuberculous and cirrhotic ascites were significantly different from one another(p<0.01). Fibronectin, sialic acid and adenosine deaminase did not show the significant overlaps among 3 groups while several other parameters-leukocyte, protein, glucose, LDH and lipids analyzed simultaneously in theses samples showed the considerable overlaps. These results suggest that determinations of fibronectin, sialic acid and adenosine deaminase in ascites may improve the accuracy of differential diagnosis of ascites.

韓國人 乳癌組織의 Estrogen 受容體의 檢索

金政徹,李洙定,鄭泰浩,朴朗韻,黃一愚 慶北大學校 醫科大學 1992 慶北醫大誌 Vol.33 No.3

한국여성의 유방암에서 estrogen수용체 및 progesterone수용체의 분포를 알아보기 위하여 39례의 유방암조직에서 이를 측정하였다. Estrogen수용체는 33.3%에서 양성으로 5.42에서 230.02f㏖/㎎ protein까지의 값을 나타내었고 progesterone수용체는 5.34내지 66.60f㏖/㎎ protein의 함량을 가진 56.4%에서 양성이었다. 폐경기 이전은 폐경기 이후에 비해 estrogen수용체와 progesterone수용체가 모두 양성인 경우가 더 많았고 모두 음성인 경우는 더 적었으며 환자의 연령이 50세 이하인 경우의 progesterone수용체 양성율은 50세 이상의 경우보다 두배 이상 높았다. 또한 액와임파절전이가 전혀없는 경우가 1개이상 전이된 경우보다 훨씬 높은 estrogen수용체 양성율을 보였으며 TNM병기 Ⅱ는 병기Ⅱ나 Ⅳ보다 estrogen수용체 및 progesterone수용체 양성율이 더 높은 것으로 나타났다. 한편 조직학적 유형과 호르몬 수용체와의 관계는 대부분이 infiltrating ductal carcinoma인 까닭에 의미 있는 결과를 얻지 못하였다. 이상의 결과에서 나타난 estrogen수용체 및 progesterone수용체와 유방암의 여러 임상적 병리조직학적 측면들과의 상관관계로 미루어 볼 때 임상검사실에서의 통상적인 호르몬수용체 측정법 확립은 유방암의 치료 및 예후판단에 매우 유용하리라 기대된다. The levels of estrogen receptors (ER) ad Progesterone receptors (PR) in 39 breast cancer tissues have been determined and a correlation of both receptor levels with the histopathologic findings and clinical features was attempted. The ER levels ranged from 0 to 230.02 fmol/㎎ cytosol protein and the PR levels ranged from 0 to 66.60 fmol/㎎ cytosol protein. 33% of the specimens were ER+ and 56% were PR+. The group younger than 50 years had a higher percentage of positive PR status. The positive rate of ER showed no significant difference between pre and postmenopause, while those of PR was decreased from 67% in pre-to 41% in postmenopause. 82% of the histologic type were infiltrating ductal carcinoma and 74% of patients were stage Ⅱ of TNM classification. These results indicated that there was strong correlation between age, menopausal status, axillary lymph node metastasis, TNM stage and receptor status.

Session F : Eukaryotic Gene Structure and Expression : Effect of Phorbol Myristate Acetate on Fibronectin Synthesis and mRNA Levels in Normal and Transformed Fibroblasts

Rang Woon Park,In San Kim,Byung Heon Lee,Young Ah Shin,Je Yong Choi,Hyun Mo Ryoo,Kun Young Sohn,Joon Seung Jo 생화학분자생물학회(구 한국생화학분자생물학회) 1993 추계학술대회집 Vol.- No.-

Erythropoietin Decreases Renal Fibrosis in Mice with Ureteral Obstruction: Role of Inhibiting TGF-β-Induced Epithelial-to-Mesenchymal Transition

Park, Sun-Hee,Choi, Min-Jeong,Song, In-Kyung,Choi, Soon-Youn,Nam, Ju-Ock,Kim, Chan-Duck,Lee, Byung-Heon,Park, Rang-Woon,Park, Kwon Moo,Kim, Yong-Jin,Kim, In-San,Kwon, Tae-Hwan,Kim, Yong-Lim American Society of Nephrology 2007 Journal of the American Society of Nephrology Vol.18 No.5

<P>The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.</P>

Caspase 9 promoter polymorphisms and risk of primary lung cancer

Park, Jae Yong,Park, Jung Min,Jang, Jin Sung,Choi, Jin Eun,Kim, Kyung Mee,Cha, Sung Ick,Kim, Chang Ho,Kang, Young Mo,Lee, Won Kee,Kam, Sin,Park, Rang Woon,Kim, In San,Lee, Jae-Tae,Jung, Tae Hoon IRL Press 2006 Human molecular genetics Vol.15 No.12

<P>Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the <I>CASP-9</I> gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [−1263A>G, −905T>G, −712C>T and −293_−275delCGTGAGGTCAGTGCGGGGA (−293del)] in the <I>CASP-9</I> promoter with the risk of lung cancer in a Korean population. The <I>CASP-9</I> genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The −1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the −1263 AA genotype or combined −1263 AA+AG genotype [adjusted odds ratio (OR)=0.64, 95% confidence interval (95% CI)=0.42–0.98, <I>P</I>=0.04 and adjusted OR=0.67, 95% CI=0.46–0.97, <I>P</I>=0.01, respectively]. For the −712C>T polymorphism, individuals with at least one −712T allele were at a significantly increased risk of lung cancer compared with those harboring the −712 CC genotype (adjusted OR=1.42, 95% CI=1.06–1.89, <I>P</I>=0.02). Consistent with the results of genotype analyses, the −1263G/−712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR=0.59, 95% CI=0.47–0.75, <I>P</I> and Bonferroni corrected <I>P</I> (<I>P</I><SUB>c</SUB>)<0.001]. Moreover, the risk of lung cancer decreased in a dose-dependent manner as the number of the G-C haplotypes increased (adjusted OR=0.60, 95% CI=0.45–0.81, <I>P</I>=0.0007 and <I>P</I><SUB>c</SUB>=0.0014 for the G-C heterozygotes and adjusted OR=0.34, 95% CI=0.17–0.68, <I>P</I>=0.0023 and <I>P</I><SUB>c</SUB>=0.0046 for the G-C homozygotes; <I>P</I><SUB>trend</SUB><0.001). The promoter assay revealed the G-C haplotype to have a significantly higher promoter activity than the −1263G/−712T and −1263A/−712C haplotypes. These results suggest that <I>CASP-9</I> promoter polymorphisms affect <I>CASP-9</I> expression and contribute to genetic susceptibility to lung cancer.</P>

Heparin–deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity

Park, Kyeongsoon,Lee, Gee Young,Kim, Yoo-Shin,Yu, Mikyung,Park, Rang-Woon,Kim, In-San,Kim, Sang Yoon,Byun, Youngro Elsevier 2006 Journal of controlled release Vol.114 No.3

<P><B>Abstract</B></P><P>A chemically modified heparin–DOCA (HD) conjugate was developed as a drug carrier for cancer therapy. HD conjugate was found to have markedly low anticoagulant activity and to form self-assembled nanoparticles in aqueous condition. We observed that HD conjugate prevented squamous cell carcinoma (SCC) and human umbilical vascular endothelial cell (HUVEC) proliferation during BrdU incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into the amphiphilic HD conjugate by physical interaction and characterized the properties of these nanoparticles using Dynamic Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study, doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor effects of nano-sized particles (range of 180 to 210?nm) at high drug-loading efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin nanoparticles displayed sustained drug release patterns. It was confirmed in vivo toxicity studies that HD conjugate did not induce unexpected side effects and that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate, doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline treated control. These results suggest that the drug-entrapped with heparin nanoparticles might provide a novel therapy for SCC.</P>

Poster Ⅱ : DIFFERENTIAL REGULATION OF PHORBOL ESTER ON COLLAGEN AND FIBRONECTING GENE EXPRESSION IN HUMAN FIBROBLASTS

Rang Woon Park,Byung Heon Lee,Je Yong Choi,Hyun Mo Ryoo,In San Kim,Joon Seung Jo 생화학분자생물학회(구 한국생화학분자생물학회) 1992 추계학술대회집 Vol.- No.-

심정지후 발생한 중증 저산소성 허혈성 뇌병증환자(Hypoxic Ischemic Encephalopathy)의 성공적인 소생

박규남,최세민,이운정,한주랑,박승현,김세경 大韓應急醫學會 1999 대한응급의학회지 Vol.10 No.1

Prediction of individual outcome after cardiopulmonary resuscitation of major medical, ethical, and socioeconomic interest but uncertain. We experienced the case that the patient got complete neurologic recovery after the 123th day from cardiac arrest, who had been suspected to go with poor prognosis because she got the findings of Glasgow Coma Scale 4, severe diffuse encephalopathy on encephalogram and generalized tonic-clonic seizure at the 4th day. Recently, a 29 year-old women who sustained from respiratory arrest induced presumably by sedative and anticonvulsant therapy for control of seizure that happened during local lidocaine anesthesia for mamoplasty was transfered to our emergency medical center from local private plastic office. Arrest time was about 20 minutes. On hospital arrival, she had a pulseless bradyasystole and no respiration. but spontaneous circulation was restored at 10 minutes after CPR started. We started cerebral oriented resuscitation including mild ;hypothermia(34℃), hemodilution, calcium channel blocker infusion. On hospital day 4, patients glasgow coma scale(GCS) was 4. On hospital day 7, Brain Magnetic Resonance Imaging(MRI) showed high signal intensity on T2W1, involving the bilateral basal ganglia. After contrast administration, marked enhancement can be seen at the lesion site. Patients glasgow coma scale(GCS) increased step by to 5 on 8th day, 7 on 14th day, 10 on 15th day, 13 on 17th day, 15 on 20th day, 40 days later the patient was discharged with minor neurologic abnormality including hand tremor, dysphonia, amenorrhea and Mini Mental State Examination (MMSE) score(26). Long-term Follow up revealed that all neurolgic functional abnormality including hand, dysphonia, amenorrhea and MMSE score(26) is completely recovered on 123th day after episode of cardiopulmonary arrest.

Keloid세포의 Collagen합성에 관한 연구

박혜경,박낭운,이병헌,최제용,김인산,조준승 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.2

목적 :이 연구의 목적은 keloid가 점점 그 주위조직으로 침범하는 성질이 있는 것에 착안하여 keloid 중심부위와 그 인접부위 그리고 정상부위 조직에서의 collagen 합성능을 측정하여 상호비교 해보는데 있다. 재료 및 방법 : 7예의 keloid 섬유아세포와 3예의 keloid 인접부위 섬유아세포 그리고 5예의 정상부위 섬유아세포를 배양하여 Peterkofsky씨등의 방법^13)에 따라 collagen 합성능을 측정하였다. 해체와 배양조건에 따른 차이를 배제하기 위하여 한 환자로부터 동시에 각 부위의 조직을 동시에 얻어 동시에 섬유아세포를 배양하였다. 결과 : Collagen 합성능의 평균값은 정상조직보다 keloid 부위에서 훨씬 높았으며 또한 keloid 부위보다 그 인접부위에서 더욱 높았다. 결론 : 섬유아세포에서의 collagen 합성능은 정상부위, keloid 부위 및 그 인접부위 순으로 더욱 높았다. 이것은 keloid 환부주위에 국소적으로 작용하는 인자들이 존재하여 이들에 의해 keloid 주위조직이 자극을 받아 collagen 합성능이 증가하게 됨을 시사한다. Keloids are predominantly fibrous skin tumors that take the form of firm, variably pruritic or tender growths near the site of an injury. Histopathologically they are ricd in various connetive tissue components, such as collagen. In this study, the collagen synthesis by fibroblasts derived from keloid, keloid-adjacent area and normal skin was analyzed. Six keloid fibroblast cell lines out of 7 demonstrated increased collagen synthesis and one showed collagen synthetic rate that was within the control limits. One keloid fibroblast cell and one normal fibroblast cell were cultured from a patient, and when their collagen synthetic rates were compared with each other it resulted in that keloid cells showed a higer synthetic rate than normal cells. Three keloid-adjacent fibrolast cell lines showed markedly incerased collagen synthesis than their corresponding keloid cell lines which were derived from the same patients. Taken together, these results suggest that in keloid lesion, there might be local factors which stimulate surrounding fibroblasts to synthesize excessive collagen.