암세포 증식에 대한 YB-1 안티센스 올리고핵산염의 영향

김명성 ( Myung Sung Kim ),이완식 ( Wan Sik Lee ),박창환 ( Chang Hwan Park ),주영은 ( Young Eun Joo ),김현수 ( Hyun Soo Kim ),최성규 ( Sung Kyu Choi ),유종선 ( Jong Sun Rew ),정영도 ( Young Do Jung ),김세종 ( Sei Jong Kim ),안봉환 대한내과학회 2006 대한내과학회지 Vol.71 No.3

목적: YB-1은 PCNA, DNA 중합효소 및 MDR 유전자 등의 전사인자로 작용한다. YB-1 유전자는 정상 어른의 간에서는 발현되지 않지만 태아의 간이나 재생 중인 간에서는 발현이 현저히 증가되어서 세포의 증식과 밀접한 관련이 있음이 보고되었다. 본 연구에서는 YB-1 유전자의 안티센스 올리고핵산염을 이용하여 YB-1의 발현을 억제함으로써 암세포 증식을 차단 할 수 있는지를 실험하고 암치료를 위한 유전자 요법으로서의 가능성을 알아보았다. 방법: 세포주로는 Chang liver, HepG2, CT-26 세포를 사용하였고, 사람의 정상세포로는 섬유아세포와 내피세포가 혼재된 조직을 사용하였다. YB-1 유전자의 안티센스 올리고핵산염으로는 YB-1 cDNA의 변역 시작 부위에 상보적인 21mer 올리고핵산염을 제작하여 사용하였다. 세포의 성장은 MTT assay를 이용하였고, 유전자 발현은 Northern blot으로 분석하였으며, 세포주기 변화는 propidium iodide로 염색하여 유식세포분석기로 분석하였다. 동물실험에서는 CT-26 세포를 1.0×10(5)개씩 Balb/c 생쥐의 피하에 접종하여 종양을 유도하였다. 종양이 유도된 Balb/c 생쥐에 YB-1 안티센스 올리고핵산염을 꼬리정맥이나 종양조직에 주사한 후 종양의 크기를 측정하여 종양억제 효과를 관찰하였다. 결과: YB-1 안티센스 올리고핵산염은 CT-26 세포에서는 50 nM 이상 농도에서 Chang liver와 HepG2 세포에서는 10 nM 이상 농도에서 세포주의 성장을 강하게 억제하였지만 정상 조직세포의 성장에는 아무런 영향을 미치지 않았다. 안티센스 올리고핵산염을 DOTAP에 담지한 경우 세포성장 억제에 미치는 효과가 안티센스 올리고핵산염 단독 처치 보다 강하였다. 이때 YB-1의 발현은 증식이 억제된 세포주(Chang liver 및 CT-26)에서는 감소하였으나 정상조직세포에서는 변화가 없었다. 증식이 억제된 세포주에서 세포주기를 살펴보면 초기에 S phase가 감소함을 관찰 할 수 있었다. 꼬리정맥이나 종양조직에 YB-1 안티센스 올리고핵산염을 주입 시 종양의 크기가 유의하게 감소하였다. 결론: 이상의 실험 결과 YB-1 안티센스 올리고핵산염은 암세포의 성장을 저해하며 종양 동물모델에서 종양의 성장을 억제할 수 있음을 시사하였다. Background: Human YB-1 is a transcription factor that binds to the inverted CCAAT box in the promoter region of a variety of genes such as PCNA, DNA polymerase and MDR. In this study we evaluated the effect of YB-1 antisense oligonucleotides on tumor cell growth. Methods: Chang liver, HepG2 and CT-26 cells were cultured as immortalized cell lines. The MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay, Northern blot and flow cytometric analyses were used to determine cell growth, gene expression and cell cycle changes. In an animal model, CT-26 cells were injected into Balb/c mice to induce tumor; YB-1 antisense oligonucleotides were injected into the tail vein or tumor tissue of the mice; change of tumor size was then measured. Results: Phosphorothioated YB-1 antisense oligonucleotides suppressed the proliferation of the immortalized liver cells (Chang liver cells) and a variety of cancer cells (HepG2 and CT-26 cells); however, it did not inhibit normal cell growth. The DOTAP/antisense oligonucleotide mixture showed stronger effects on cell proliferation than did the antisense oligonucleotide alone. The YB-1 antisense oligonucleotide decreased specific expression of the YB-1 mRNA in the immortalized cancer cell lines. Flow cytometric analysis revealed that the inhibition of cell proliferation might have been due to a decrease in the S phase of the cell cycle. We found that in an animal tumor model, the administration of the YB-1 antisense oligonucleotide, in the vein or tumor tissues, decreased the tumor size significantly. Conclusions: These results suggest that the YB-1 antisense oligonucleotide may inhibit growth of a variety of cancer cells.(Korean J Med 71:293-301, 2006)

妊産婦에 있어서의 眼底變化

李明秀,金順昌,趙炳釵 최신의학사 1961 最新醫學 Vol.4 No.1

Dipyridamole 부하 심근 SPECT에서 Dipyridamole의 작용과 부작용

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),최창운(Chang Woon Choi),배상균(Sang Kyun Bae),양형인(Hyung In Yang),여정석(Jeong Suk Yeo) 대한핵의학회 1993 핵의학 분자영상 Vol.27 No.2

N/A Dipyridamole is an agent that may be used to noninvasively evaluate coronary artery disease. The effect of dipyridamole infusion its generally related to its induced peripheral vasodilatory effect. In normal person, heart rate is generally increased slightly while blood pressure decrease, but the achieved double product and related myocardial oxygen consumption have no significant change. The purpose of this study is to examine the effect and side effect of dipyridamole, and to compare different response to dipyridamole among the patients. We evaluated 847 patients who underwent dipyridamole stress myocardial SPECT. 93.6% of them had induced hypotension 0.9% showed no change of blood pressure, 5.5% had increased blood pressure 8.3% had no change of pulse rate more than 10% of basal pulse rate. Among diabetes, 16.9% was not change of pulse rate, 6.7% in non-diabetes. There was no significant correlation between age and rate pressure product rest(RPPr), in patients without perfusion defects on SPECT(y=7.1x+48.4r=0.13 p>0.01). As increasing age, RPPs/RPPr was declined(y=-11.6x+68.9 r=0.17 p〈0.01), similar results were obtained in patients with perfusion defect. The size of perfusion defect on myocardial SPECT have no correlation between RPPr and RPPs/RPPr. The side effects of dipyridamole included chest pain and chest tightness, headache, abdominal pain, dizzness, nausea, and dyspnea. As increasing age, dipyridamole-induced cardiac work at rest was increased, cardiac response to dipyridamole was decreased.

Al³^(+) 존재가 ^(99m)Tc-MDP의 표지효율과 생체내 분포에 미치는 영향

장영수,정재민,김영주,곽철은,이동수,정준기,이명철,고창순 大韓核醫學會 1996 핵의학 분자영상 Vol.30 No.3

안구적출에 따른 위둔덕의 Calbindin D-28k과 c-fos의 변화에 관한 연구

김명,김기훈,김주영,하현철,안명수,김장민,조향훈,정명섭,장인엽 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.2

Changes of Calbindin D-28k- and c-fos-immunoreactivities in the superior collicuclus after Eye Enucleation. Objective and methods: Calcium-binding proteins (CBPs) play an important role in the protection, differentiation and reorganization of the central nervous system. The effects of neonatal retinal deafferentation on a CBPs, calbindin D-28k were examined immunohistochemically in the superficial layer of the rat superior colliculus. Also early gene familly c-fos was examined to evaluate the neuronal characteristics in the superior colliculus after monocular enucleation. Results: On the experimental side of superior colliculus, the number of calbindin D-28k-immunoreactive (IR) cells was reduced (77.4% compared to control), but not fibers. Appearance of c-fos-like immunoreactivity was represented much more in the ipsilateral superior colliculus than contralateral side within 24h after eye enucleation. Conclusion: These results suggest that the changes of retinotectal projection may alter the expressional pattern of calbindin D-28k and c-fos expression.

오징어젓 숙성 중 제4급 암모늄 화합물의 변화

김성수,오창경,오명철,송대진,김수현 濟州大學校 産業技術硏究所 1996 산업기술연구소논문집 Vol.7 No.1

The changes in precursors of N-nitrosarnines, such as choline-N, betaine-N and total creatinine-N, during the fermentation of high salt-fermented squid, sepiell maindroni, group with 20% of salt and low salt-fermented squid group with 10% of salt, 6% of ethanol, 6% of sorbitol and 0.5% of lactic acid were investigated. During the fermentation, the contents of VBN were rapidly increased from the beginning of the fermentation until 140 days, and these contents were more in high salt groups as compared with low salt groups. The contents of choline-N were little changed until 80 days of the fermentation and slowly decreased after 80 days of the fermentation to 120 days, but the different of the contents between both salt groups were little. Betaine-N also showed the similar tendency to choline-N, but the changes in low salt groups were slowly increased and decreased as compared with these in high salt group. Total creatinine-N was slowly increased from the beginning of the fermentation until 60 days in both salt groups, but rapidly decreased after this to 120 day.

오징어젓 숙성 중 제4급 암모늄 화합물의 변화

김성수,송대진,오명철,오창경,김수현 濟州大學校工科大學産業技術硏究所 1996 尖端技術硏究所論文集 Vol.7 No.1

The changes in precursors of N-nitrosamines, such as choline-N, betaine-N and total creatinine-N, during the fermentation of high salt-fermented squid, Sepiell maindroni, group with 20% of salt and low salt-fermented squid group with 10% of salt, 6% of ethanol, 6% of sorbitol and 0.5% of lactic acid were investigated. During the fermentation, the contents of VBN were rapidly increased from the beginning of the fermentation until 140 days, and these contents were more in high salt groups as compared with low salt groups. The contents of choline-N were little changed until 80 days of the fermentation and slowly decreased after 80 days of the fermentation to 120 days, but the different of the contents between both salt groups were little. Betaine-N also showed the similar tendency to choline-N, but the changes in low salt groups were slowly increased and decreased as compared with these in high salt group. Total creatinine-N was slowly increased from the beginning of the fermentation until 60 days in both salt groups, but rapidly decreased after this to 120 day.

오징어젓 숙성 중 N-nitrosamine 생성에 관한 연구

김성수,오창경,오명철,송대진,김수현 濟州大學校 産業技術硏究所 1996 산업기술연구소논문집 Vol.7 No.1

Possibility of formation of carcinogenic N-nitrosamines and changes in their precursors during the fermentation of high salt-fermented squid, Sepiell maindroni, group with 20% of salt and low salt-.fermented squid group with 10% of salt, 6% of ethanol, 6% of sorbitol and 0.5% of lactic acid were investigated. pH during the fermentation of squid changed in the ranges of 5.79 ~6.07 and 6.05~6.21 in low and high salt group, respectively. The contents of nitrite- and nitrate-N during the fermentation were in the ranges 0.75~1.04 and 1.22~1.42mg/kg, respectively. Trimethylamine(TMA) was continuously .increased during the fermentation and showed 20.1 and 14.9mg% in high and low salt group after 140 days of the fermentation, respectively. while trimethylamine oxide(TMA0) was gradually increased from the beginning until the middle period of fermentation and then was again decreased. Dimethylamine(DMA) was continuously increased during the fermentation and showed 19.7 and 13.3mg/kg in high and low salt group after 140 days of the fermentation, respectively. N-nitrosamines in salt-fermented squid was detected only N-nitrosodimethylamine(NDMA), which its amount was trace in low salt group and 3.8~g/kg in high salt group on 40 days of the fermentation and then continuously increased in the ranges of 57.5~74.7μg/kg in both groups during the fermentation.

Control of Reversible Self-Bending Behavior in Responsive Janus Microstrips

Oh, Myung Seok,Song, Young Shin,Kim, Cheolgyu,Kim, Jongmin,You, Jae Bem,Kim, Taek-Soo,Lee, Chang-Soo,Im, Sung Gap American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.13

<P>Here, we demonstrate a simple method to systematically control the responsive self-bending behavior of Janus hydrogel microstrips consisting of a polymeric bilayer with a high modulus contrast. The Janus hydrogel microstrips could be easily fabricated by a simple micromolding technique combined with an initiated chemical vapor deposition (iCVD) coating, providing high flexibility in controlling the physical and chemical properties of the microstrips. The fabricated Janus hydrogel microstrip is composed of a soft, pH-responsive polymer hydrogel layer laminated with a highly cross-linked, rigid thin film, generating a geometric anisotropy at a micron scale. The large difference in the elastic moduli between the two layers of the Janus microstrips leads to a self-bending behavior in response to the pH change. More specifically, the impact of the physical and chemical properties of the microstrip on the self-bending phenomena was systematically investigated by changing the thickness and composition of two layers of the microstrip, which renders high controllability in bending of the microstrips. The curvature of the Janus microstrips, formed by self-bending, highly depends on the applied acidity. A reversible, responsive self-bending/ unbending exhibits a perfect resilience pattern with repeated changes in pH for 5 cycles. We envision that the Janus microstrips can be engineered to form complex 3D microstructures applicable to various fields such as soft robotics, scaffolds, and drug delivery. The reliable responsive behaviors obtained from the systematic investigation will provide critical information in bridging the gap between the theoretical mechanical analysis and the chemical properties to achieve micron-scale soft robotics.</P>

오징어젓 숙성 중 N-nitrosamine 생성에 관한 연구

오창경,김수현,송대진,오명철,김성수 濟州大學校工科大學産業技術硏究所 1996 尖端技術硏究所論文集 Vol.7 No.1

본 연구는 오징어에 식염 20%를 첨가하는 고식염구와 식염 10%에 솔비톨, 에탄올, 젖산 등을 첨가한 저식염구로 나누어 오징어젓을 제조한 후, 이들을 숙성시키면서 N-nitrosamine의 생성 여부와 숙성 중 그의 전구물질인 아질산염과 질산염, DMA 및 TMA와 TMAO의 변화를 검토하였다. 오징어젓 숙성 중 pH는 저식염구가 5.79∼6.07, 고식염구가 6.05∼6.21 사이에서 변화하였다. 아질산염질소와 질산염질소는 각각 0.75∼1.04mg/kg 및 1.22∼1.42mg/kg 사이에서 변화하였다. TMA-N는 숙성 중 계속하여 증가하여 숙성 140일에는 고식염구가 20.1mg%, 저식염구가 14.9mg%였으며, TMAO-N는 생시료에서 27.9mg%이었던 것이 숙성 중기까지 완만하게 증가하다가 그 이후에는 다시 감소하였다. DMA-N는 숙성 중 계속하여 증가하였으며 숙성 140일에는 고식염구는 19.7mg/kr, 저식염구는 13.3mg/kg이었다. 오징어젓의 N-nitrosamine으로는 NDMA만이 검출되었고, 숙성 40일째에 저식염구에 흔적량, 고식염구에 3.8㎍/kg의 양으로 생성되었으며 숙성 중 계속해서 증가하여 57.5∼74.7㎍/kg에 이르렀다. Possibility of formation of carcinogenic N-nitrosamines and changes in their precursors during the fermentation of high salt-fermented squeid, Sepiell maindroni, group with 20% of salt and low salt-fermented squid group with 10% of salt, 6% of ethanol, 6% of sorbitol and 0.5% of lactic acid were investigated. pH during the fermentation of squid changed in the ranges of 5.79∼6.07 and 6.05∼6.21 in low and high salt group, respectively. The contents of nitrite- and nitrate-N during the fermentation were in the ranges 0.75∼1.04 and 1.22∼1.42mg/kg, respectively. Trimethylamine(TMA) was continuously increased during the fermentation and showed 20.1 and 14.9mg% in high and low salt group after 140 days of the fermentation, respectively, while trimethylamine oxide(TMAO) was gradually increased from the beginning until the middle period of fermentation and then was again decreased. Dimethylamine(DMA) was continuously increased during the fermentation and showed 19.7 and 13.3mg/kg in high and low salt group after 140 days of the fermentation, respectively. N-nitrosamines in salt-fermented squid was detected only N-nitrosodimethylamine(NDMA), which its amount was trace in low salt group and 3.8㎍/kg in high salt group on 40 days of the fermentation and then continuously increased in the ranges of 57.5∼74.7㎍/kg in both groups during the fermentation.