Tamoxifen Induces Mitochondrial-dependent Apoptosis via Intracellular Ca²⁺ Modulation

장은성,김지영,김병기,Jang, Eun-Seong,Kim, Ji-Young,Kim, Byeong-Gee Korean Society of Life Science 2007 생명과학회지 Vol.17 No.8

유방암 치료제로 사용되는 탐옥시펜 (Tam)은 MCF-7 세포주에서 세포증식을 억제하며 세포사멸을 유도한다. 본 연구에서는 Tam의 세포독성 효과가 세포 내 칼슘이온 농도 증가에 따른 미토콘드리아-의존 기작에 의하여 일어난다는 것을 보여준다. Tam에 의해 유도된 세포 내 칼슘이온 농도 증가는 주로 외부로부터의 칼슘 유입에 의한 것으로 생각된다. 칼슘 채널 억제제를 이용한 실험 결과에 의하며, 칼슘 증가 초기 단계는 주로 전압의존 칼슘채널에 의한 것이며 후기에는 세포 내 저장된 칼슘의 유출, 혹은 다른 방법에 의한 칼슘 유입으로 생각된다. Tam에 의한 세포 내 칼슘 증가는 미토콘드리아로부터의 cytochrome c 방출과 미토콘드리아막의 탈분극에 의한 membrane potential 변화를 초래하였다. 세포사멸에 주도적인 역할을 하는 caspase의 확인에 있어서는, MCF-7 세포는 caspase-3이 결핍되어서 caspase-7이 중심적인 역할을 하는 것으로 이미 알려져 있다. 본 연구에서 확인한 결과 Tam 처리시 caspase-7이 활성화되었으며, 또한 세포사멸 조절 단백질인 Bcl-2 종류 단백질들의 발현을 조사 한 결과 세포사멸 억제 단백질인 Bcl-2의 발현에는 변화가 없었으나 촉진단백질인 Bax는 Tam 처리시 단백질 양이 2배로 증가되었다. 이상의 결과에 의하면, Tam에 의해 유도되는 세포사멸과정은 세포질 내 칼슘이온 농도증가에 의한 미토콘드리아의 변화가 주도적인 역할을 하는 것으로 생각된다. In the present work, we show that tamoxifen(Tam)-induced cytotoxicity is due to the mitochondrial-dependent pathway triggered by the intracellular $Ca^{2+}$ increase in MCF-7 human breast cancer cells. Tam induced the intracellular $Ca^{2+}$ increase. According to the experimental results with $Ca^{2+}$ channel blockers, Tam-induced $Ca^{2+}$ uptake seemed to depend on the voltage-sensitive $Ca^{2+}$ channel at the early stage, but at later stages the intracellular $Ca^{2+}$ increases are more likely due partly to the release of stored $Ca^{2+}$ and partly to the capacitative $Ca^{2+}$ or other entry pathways. Tam-induced $Ca^{2+}$ increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with Tam, caspase-7 cleavage was increased almost two-fold. There was no marked alteration in the level of anti-apoptotic Bcl-2 protein; however, the cells showed increased expression of pro-apoptotic Bax protein more than two-fold in response to Tam. These results imply that the apoptotic signaling pathway activated by Tam is likely to be mediated via the mitochondrial-dependent pathway.

발전된 방사선 치료에 관한 고찰

장은성,백성민,고성진,강세식,Jang, Eun-Sung,Beak, Seong-Min,Ko, Seung-Jin,Kang, Se-Sik 대한방사선치료학회 2008 대한방사선치료학회지 Vol.20 No.2

Purpose: The cancer treatment which uses radiation from next year when the X-ray is discovered with the fact that it is started. The radiation treatment technique for a cancer treatment is developed ceaselessly without and it is come and, with advancement of the computer and electromagnetic engineering it joins in and quickly, it was made to do a many development from radiation treatment field. Accordingly, this study is examine in the radiotherapy technique which is developed that importance to therapeutic principles and methods. Materials and Methods: We had investigated record for radiotherapy technique which is developed and we had acquired information widely at clinical experience data. Results: The cancer treatment which uses the radiation of today is repeating a dazzling development. Past the treatment which is two-dimensional it does not correspond in therapeutic objective but currently 3 dimension three-dimensional moulding treatment or centurial control radiation treatment this the fourth dimension therapeutic technique which is in parallel to be introduced the complication solution in compliance with a normal organization protection and the radiation which are a difficult problem of during that time radiation treatment possibly did. Conclusion: 3-dimensional and 4-dimensional modern radiation treatment which is developen is that corresponding in objective of radiation treatment and the evaluation that again it does thick, judges in about the cancer treatment which uses radiation with the fact that the protection of normal organization is almost become accomplished.

Mechanism of Apoptosis Induced by Spermine in MCF-7 Breast Cancer Cells

Eun Seong Jang(장은성),Byeong Gee Kim(김병기) 한국생명과학회 2008 생명과학회지 Vol.18 No.9

폴리아민은 미생물에서부터 동ㆍ식물에 이르기 까지 모든 세포들에서 발견되는 극성을 띈 분자이다. 세포의 성장과 분화에 폴리아민이 중요한 역할을 한다는 것은 이미 오래 전부터 알려져 온 사실이나 정확한 작용 기작은 잘 밝혀져 있지 않다. 최근에 와서는 폴리아민이 다양한 방법으로 세포 독성을 유발한다는 결과가 보고되고 있다. 본 연구에서는 spm의 세포독성 효과가 세포 내 칼슘이온 농도 증가에 따른 미토콘드리아-의존 기작에 의하여 일어난다는 것을 보여준다. Spm에 의해 유도된 세포 내 칼슘이온 농도 증가는 주로 외부로부터의 칼슘 유입에 의한 것으로 생각되며, 세포 내 칼슘 증가는 미토콘드리아로부터의 cytochrome c 방출과 미토콘드리아막의 탈분극에 의한 membrane potential 변화를 초래하였다. 세포사멸에 주도적인 역할을 하는 caspase의 확인에 있어서는, MCF-7 세포는 caspase-3이 결핍되어서 caspase-7이 중심적인 역할을 하는 것으로 이미 알려져 있다. 본 연구에서 확인 한 결과 spm 처리 시 caspase-7과 -12가 활성화되었다. 또한 세포사멸 조절 단백질인 Bcl-2 종류 단백질들의 발현을 조사 한 결과 세포사멸 억제 단백질인 Bel-2의 발현은 크게 억제되었으며, 촉진단백질인 Bax는 spm 처리시 단백질 양이 거의 2배로 증가되었다. 이상의 결과에 의하면, spm에 의해 유도되는 세포사멸과정은 세포질 내 칼슘이온 농도 증가에 의한 미토콘드리아의 변화가 주도적인 역할을 하는 것으로 생각된다. In the present work, we show that spermine (spm)-induced cytotoxicity is due to the mitochondrial-dependent pathway triggered by the intracellular Ca²? increase in MCF-7 human breast cancer cells. Spm induced the intracellular Ca²? increase in a dose-dependent manner in the medium containing 1.5 mM Ca²?. Even in the Ca²?-free medium, spm could induce a minor Ca²? increase in a dose-dependent fashion, suggesting a probable leak from the internal storage. The cytotoxic effect of Ca²? could be further proved by using either BAPTA or ionophore. Spm-induced Ca²? increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with spm, the cleavage of caspase-7 and -12 was increased almost two-fold. The level of anti-apoptotic Bcl-2 protein decreased to 35% of the control; however, the cells showed increased expression of pro-apoptotic Bax protein about two-fold in response to spm. These results imply that the apoptotic signaling pathway activated by spm is likely to be mediated via the mitochondrial-dependent pathway.

환경시료의 방사능 측정에서 HPGe 검출기의 전에너지 피크효율 곡선에 관한 고찰

장은성 ( Eun Sung Jang ),백성민 ( Seong Min Baek ) 한국환경분석학회 2010 환경분석과 독성보건 Vol.13 No.4

Standard radioactive sources that are used in determining the efficiency of detectors used single nuclide standard radioactive sources that are composed of single gamma nuclides containing total energy area (60-1863 keV), including environmental soil samples for environmental monitoring with a purpose of controlling radioactive. By measuring standard radioactive sources of diverse geometric shape of measuring containers (cylindricalMarinelli type: 40, 450 and 1000ml) calculated full-energy peak efficiency of HPGe detectors, and compared this with full-energy peak efficiency of environmental sample soil. Spectrum was ready to measure gamma energy up to 3 MeV in 8192 (16384) channels with measuring time 20000 seconds. The detectors used in the experiments was from coaxial HPGe detectors of EG&G ORTEC. For 1332.5keV of gamma rays in 60Co, the energy resolving power is 1.8keV, relative efficiency 30%, and peak/Compton ratio 51/1. Furthermore, when apply to environmental samples, for high energy area (>1000 keV), it waswithin allowable error range of 4%, and the efficiency curves showed having uncertainties less than 4% within energy 60-1863keV. In addition to this, it was proven that it is effective in standard radioactive sources that are used in environmental monitoring around nuclear facilities. Thus it is considered that this might be highly effective in analyzing wide range of gamma spectrum including routine environmental sample measurement or in monitoring in case of emergency situation etc.

Gafchromic $EBT^{(R)}$ 필름을 이용한 선량분포의 평가

강세식,고성진,장은성,Kang, Se-Sik,Ko, Seong-Jin,Jang, Eun-Sung 대한방사선과학회 2007 방사선기술과학 Vol.30 No.2

Gafchromic $EBT^{(R)}$ 필름을 이용하여 정위방사선수술에서 작은 조사야에 대한 선량분포를 측정, 분석하는데 있어 그 유용성을 평가하였다. 조직 등가물질인 water 팬톰의 diode와 아크릴 팬톰내의 $EBT^{(R)}$ 필름을 비교하였으며, 또한 실제 뇌정위방사선수술의 평가를 위해 Gafchromic $EBT^{(R)}$ 필름을 이용하여 인체모형 두부 팬톰내 치료부위 위치를 확인하고 선량을 측정하여 계산값과 비교하였다. diode와 $EBT^{(R)}$ 필름 모두 1.5cm에서 6MV 광자선에 대한 Dmax가 있었으며 팬톰내의 깊은 영역으로 빔이 진행하면 $10{\sim}20\;cm$서 두 측정방법 모두 $2{\sim}3%$ 정도의 오차로 중심에서 벗어나는 경향을 보여주고 있었다. Gafchromic $EBT^{(R)}$ 필름의 실제 조사된 선량분포를 치료계획에서 결정된 선량분포와 비교하면 90% 등선량곡선에서 5% 정도의 차이가 있음을 확인할 수 있었다. 뇌정위방사선수술에서 팬톰을 이용하여 측정한 주어진 목표점에서의 방사선 조사선량이 정확하게 측정된다는 사실을 확인하였으며 또한 정도관리의 한 방법으로도 그 유용성이 확인되었다. Dose evaluation for small field such as stereotactic radiosurgery was performed using $Gafchromic^{(R)}$ EBT film. Every film which irradiated 6MV photon beam was scanned and obtained the optical density(OD) by flat bed scanner after 24 hours of irradiation. This study compared dose from diode in water and Gafchromic $EBT^{(R)}$ film in acrylic phantom to verify the reliability of the film, and to evaluate the SRS in clinical dose distributions from calculation and measurement in the region of virtual target in humanoid and cylindrical phantoms were compared. The Gafchromic $EBT^{(R)}$ film was found to be linear up to 9Gy. The $D_{max}$ for 6 MV was measured at 1.5 cm from the surface by both of diode and the film. As the depth is deeper, the error was measured within $2{\sim}3%$ at $10{\sim}20\;cm$ depth. Comparing between distribution from calculation and measurement, we found that there is 5% error at 90% isodose line. We found that given dose could be measured accurately by using the phantoms. It was feasible to use the Gafchromic $EBT^{(R)}$ film in quality assurance of SRS.

Gafchromic EBTⓇ 필름을 이용한 선량분포의 평가

강세식(Se-Sik Kang),고성진(Seong-Jin Ko),장은성(Eun-Sung Jang) 대한방사선과학회(구 대한방사선기술학회) 2007 방사선기술과학 Vol.30 No.2

  Gafchromic EBT<SUP>?</SUP> 필름을 이용하여 정위방사선수술에서 작은 조사야에 대한 선량분포를 측정, 분석하는데 있어 그 유용성을 평가하였다.<BR>  조직 등가물질인 water 팬톰의 diode와 아크릴 팬톰내의 EBT<SUP>?</SUP> 필름을 비교하였으며, 또한 실제 뇌정위방사선수술의 평가를 위해 Gafchromic EBT<SUP>?</SUP> 필름을 이용하여 인체모형 두부 팬톰내 치료부위 위치를 확인하고 선량을 측정하여 계산값과 비교하였다.<BR>  diode와 EBT<SUP>?</SUP> 필름 모두 1.5㎝에서 6MV 광자선에 대한 Dmax가 있었으며 팬톰내의 깊은 영역으로 빔이 진행하면 10~20㎝서 두 측정방법 모두 2~3% 정도의 오차로 중심에서 벗어나는 경향을 보여주고 있었다.Gafchromic EBT<SUP>?</SUP> 필름의 실제 조사된 선량분포를 치료계획에서 결정된 선량분포와 비교하면 90% 등선량곡선에서 5% 정도의 차이가 있음을 확인할 수 있었다.<BR>  뇌정위방사선수술에서 팬톰을 이용하여 측정한 주어진 목표점에서의 방사선 조사선량이 정확하게 측정된다는 사실을 확인하였으며 또한 정도관리의 한 방법으로도 그 유용성이 확인되었다.   Dose evaluation for small field such as stereotactic radiosurgery was performed using Gafchromic<SUP>?</SUP> EBT film. Every film which irradiated 6MV photon beam was scanned and obtained the optical density(OD) by flat bed scanner after 24 hours of irradiation. This study compared dose from diode in water and Gafchromic EBT<SUP>?</SUP> film in acrylic phantom to verify the reliability of the film, and to evaluate the SRS in clinical dose distributions from calculation and measurement in the region of virtual target in humanoid and cylindrical phantoms were compared.<BR>  The Gafchromic EBT<SUP>?</SUP> film was found to be linear up to 9㏉. The Dmax for 6MV was measured at 1.5㎝ from the surface by both of diode and the film. As the depth is deeper, the error was measured within 2~3% at 10~20㎝ depth. Comparing between distribution from calculation and measurement, we found that there is 5% error at 90% isodose line.<BR>  We found that given dose could be measured accurately by using the phantoms. It was feasible to use the Gafchromic EBT<SUP>?</SUP> film in quality assurance of SRS.

영화 "셰익스피어 인 러브"에 나타난 의상분석

박춘순 ( Chun Sun Park ),서미영 ( Mi Young Suh ),서미희 ( Mi Hi Su ),장은성 ( Eun Seong Jang ) 충남대학교 생활과학연구소 2002 忠南生活科學硏究誌 Vol.15 No.-