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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.
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Evaluation of the Anti-Tumor Effects of Paclitaxel-Encapsulated pH-Sensitive Micelles
한종권,김민상,김유신,박랑운,박낭운,권익찬,이두성 한국고분자학회 2009 Macromolecular Research Vol.17 No.2
We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly(β-amino ester) (PEG-PAE), as carriers for paclitaxel (PTX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.
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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.
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HaqueMohammadEnamul,Fatima Khan,Lianhua Chi,Smriti Gurung,Sri Murugan Poongkavithai Vadevoo,박랑운,김동규,김상균,이병헌 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3
Purpose This study was carried out to identify a peptide that selectively binds to kidney injury molecule- 1 (KIM-1) by screening a phage-displayed peptide library and to use the peptide for the detection of KIM-1–overexpressing tumors in vivo. Materials and Methods Biopanning of a phage-displayed peptide library was performed on KIM-1–coated plates. The binding of phage clones, peptides, and a peptide multimer to the KIM-1 protein and KIM-1–overexpressing and KIM-1–low expressing cells was examined by enzyme-linked immunosorbent assay, fluorometry, and flow cytometry. A biotin-peptide multimer was generated using NeutrAvidin. In vivo homing of the peptide to KIM-1–overexpressing and KIM- 1–low expressing tumors in mice was examined by whole-body fluorescence imaging. Results A phage clone displaying the CNWMINKEC peptide showed higher binding affinity to KIM-1 and KIM-1–overexpressing 769-P renal tumor cells compared to other phage clones selected after biopanning. The CNWMINKEC peptide and a NeutrAvidin/biotin-CNWMINKEC multimer selectively bound to KIM-1 over albumin and to KIM-1–overexpressing 769-P cells and A549 lung tumor cells compared to KIM-1–low expressing HEK293 normal cells. Colocalization and competition assays using an anti–KIM-1 antibody demonstrated that the binding of the CNWMINKEC peptide to 769-P cells was specifically mediated by KIM-1. The CNWMINKEC peptide was not cytotoxic to cells and was stable for up to 24 hours in the presence of serum. Whole-body fluorescence imaging demonstrated selective homing of the CNWM-INKEC peptide to KIM-1–overexpressing A498 renal tumor compared to KIM- 1–low expressing HepG2 liver tumor in mice. Conclusion The CNWMINKEC peptide is a promising probe for in vivo imaging and detection of KIM-1– overexpressing tumors.
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