• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1715-1720
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• 2013

Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2012년도 제42회 동계 정기 학술대회 초록집
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• pp.434-435
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• 2012

Plasma enhanced chemical vapor deposition (PECVD) silicon dioxide thin films have many applications in semiconductor manufacturing such as inter-level dielectric and gate dielectric metal oxide semiconductor field effect transistors (MOSFETs). Fundamental chemical reaction for the formation of SiO2 includes SiH4 and O2, but mixture of SiH4 and N2O is preferable because of lower hydrogen concentration in the deposited film [1]. It is also known that binding energy of N-N is higher than that of N-O, so the particle generation by molecular reaction can be reduced by reducing reactive nitrogen during the deposition process. However, nitrous oxide (N2O) gives rise to nitric oxide (NO) on reaction with oxygen atoms, which in turn reacts with ozone. NO became a greenhouse gas which is naturally occurred regulating of stratospheric ozone. In fact, it takes global warming effect about 300 times higher than carbon dioxide (CO2). Industries regard that N2O is inevitable for their device fabrication; however, it is worthwhile to develop a marginable nitrous oxide free process for university lab classes considering educational and environmental purpose. In this paper, we developed environmental friendly and material cost efficient SiO2 deposition process by substituting N2O with O2 targeting university hands-on laboratory course. Experiment was performed by two level statistical design of experiment (DOE) with three process parameters including RF power, susceptor temperature, and oxygen gas flow. Responses of interests to optimize the process were deposition rate, film uniformity, surface roughness, and electrical dielectric property. We observed some power like particle formation on wafer in some experiment, and we postulate that the thermal and electrical energy to dissociate gas molecule was relatively lower than other runs. However, we were able to find a marginable process region with less than 3% uniformity requirement in our process optimization goal. Surface roughness measured by atomic force microscopy (AFM) presented some evidence of the agglomeration of silane related particles, and the result was still satisfactory for the purpose of this research. This newly developed SiO2 deposition process is currently under verification with repeated experimental run on 4 inches wafer, and it will be adopted to Semiconductor Material and Process course offered in the Department of Electronic Engineering at Myongji University from spring semester in 2012.

• 생명과학회지
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• 제23권7호
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• pp.926-932
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• 2013

글루타민과 혈청은 세포의 생존과 증식에 기본적으로 요구되지만, 그들의 양적 변화에 따른 내피세포 반응에 관한 신호전달 관련 연구는 거의 이루어지지 않았다. 본 연구에서는 인체 재대정맥 내피세포(human umbilical vein endothelial cells, HUVECs)의 증식에 미치는 글루타민과 혈청의 결핍에 관한 영향을 조사하였다. 본 연구의 결과에 의하면 글루타민 및 혈청이 결핍된 조건에서 배양된 HUVECs의 증식 억제는 apoptosis 유발과 연관성이 있었음을 DAPI staining에 의한 핵의 형태 변화와 유세포 분석을 통하여 확인하였다. 비록 혈청이 결핍된 조건보다 글루타민 결핍에 의한 apoptosis 유발 정도가 더 높게 나타났으나, 두 현상에 의한 apoptosis의 유발은 anti-apoptotic Bcl-2 및 Bcl-xL의 발현 저하와 pro-apoptotic Bax의 발현 증가, IAP family 단백질의 발현 감소, caspase의 활성 증가에 따른 PARP 단백질의 단편화와 연관성이 있었다. 또한 이러한 조건에서 HUVECs의 Bid 발현의 감소 또는 tBid 발현의 증가 현상이 관찰되어, 글루타민 또는 혈청 결핍에 의한 HUVECs의 apoptosis 유발은 세포막 수용체 및 미토콘드리아 활성 경로를 동시에 통하여 이루어지고 있음을 알 수 있었다. 그러나 글루타민과 혈청이 동시에 결핍된 조건에서 배양된 HUVECs의 증식 억제 현상은 각각의 조건에 비하여 증가되었으나 apoptosis는 유발되지 않았다.

• Tuberculosis and Respiratory Diseases
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• 제60권3호
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• pp.304-313
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• 2006

연구배경 : Heme oxygenase-1 (HO-1)은 heme의 분해 대사과정에 관여하는 유도성 효소로 heme을 분해하여 biliverdin, free iron, 및 일산화탄소 등을 생성시킨다. HO-1의 발현은 다양한 스트레스성 자극에 반응하여 생체방어 기능을 갖는 것으로 알려져 있는데 세포성장이나 세포사 특히 세포고사를 조절하는 것으로 보고되고 있다. 현재 신장암, 전립선암, 간암, 육종 등의 고형암에서 발현됨이 알려져 있고, 실제 HO-1 억제제를 투여했을 때 암성장이 억제됨이 보고되었다. 저자들은 폐암세포주들에서 HO-1의 발현유무와 그 역할을 규명하고 나아가 HO-1 억제제의 치료제로서의 가능성을 알아보고자 하였다. 방 법 : 비소세포폐암세포주인 A549, H23, NCI-H157, NCI-H460을 이용하였다. 세포독성은 MTT 방법으로 구하였고, HO-1의 발현은 Western blotting으로 확인하였다. HO의 효소활성은 시간당 세포단백질의 mg당 형성된 빌리루빈의 양을 이용하여 측정하였다. 또한 $H_2O_2$의 생성은 horse radish peroxidase(HRP)와 형광물질인 2',7'-dichlorofluorescein(DCF)를 이용한 두 가지 방법을 이용하였다. A549세포에 HO-1 small interfering RNA(siRNA)을 주입하여 유식세포 분석과 caspase-3에 대한 Western blotting을 통하여 세포고사유무를 확인하였다. 결 과 : 비처리 상태에서 다른 세포주에 비해 A549세포의 HO-1 발현이 증가되었으며 HO-1 활성억제제인 ZnPP를 처리하였을 때 생존율의 의미 있는 감소를 보였다. 이러한 소견과 일치하여 ZnPP는 용량의존적으로 HO 의 효소활성 감소와 세포 내 $H_2O_2$ 생성의 증가를 초래하였다. 또한 HO-1 siRNA로 주입된 A549세포는 세포고사를 유도하였다. 결 론 : HO-1은 폐암의 치료에 있어서 새로운 분자생물학적 기전의 가능성을 제시하여 HO-1에 대한 표적치료의 가능성을 보여줄 것으로 기대된다.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.172-180
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• 2007

[ $^{15}O$ ]을 이용한 양전자 방출 단층촬영 기법(Positron emission tomography)은 핵의학 영상 기법 중에서 두뇌의 인지 기능과 연관된 두뇌 활성화를 정상인과 환자들로부터 연구하는데 큰 장점이 있다. $^{15}O-PET$, 특히 $H_2^{15}O$ PET 기법은 두뇌 국소 혈류 변화(rCBF; regional brain flow)를 상대적으로 비침습적이면서 동시에 정량적 측정할 수 있기 때문에 두뇌 기능을 연구하는데 오늘날 존재하는 핵의학 영상기법 중에서 가장 광범위하게 쓰이고 있다. 특히 $^{15}O$은 짧은 반감기로 인하여, 동일한 피험자를 서로 다른 과제 조건에서 반복적으로 측정하는 것이 가능하다. 이 PET기법은 fMRI와 같은 다른 기능 영상 기법에 비하여 기술적 제한이 있는데, 예를 들면 시간과 공간 해상도가 좋지 않다든지, 개인 데이터를 분석하기에 통계적 효율성이 부족하다거나 하는 문제이다. 그러나 최근에 3D 획득방법 같은 기술적인 발전으로 적은 양의 방사능 dose로 좋은 영상을 획득하는 것이 가능하게 되었고, 이는 다시 개개인으로부터 더 많은 수의 PET 스캔을 획득하는 것을 가능하게 하며, 결과적으로 개인 데이터의 분석이 가능한 통계적 효율성을 제공하게 되었다. 그 외에 $^{15}O$ PET 의 스캐너 환경이 소음에서부터 자유롭다던가, 개개 스캔이 각 과제 조건에서 불연속적이지 획득되기 때문에 상태 특정적 두뇌 변화를 연구하기에 유리하다는 PET연구 만의 장점이 있다. 본 종설에서는 정상인들이나 임상적 환자 집단을 사용한 예시적 연구들을 들어 $^{15}O$ PET의 장점과 한계를 논하고, 두뇌 활성화 연구에 효율적인 PET 연구 절차를 고안하기 위해 고려해야 할 사항들에 대하여 논하였다.TEX>$29.9{\pm}1.8%$, DMF: $7.6{\pm}0.5%$이었다. MEK에서 얻은 $[^{11}C]1$의 비방사능은 98 ($GBq/{\mu}mol$)이다. 각 물질의 질량 분석은 1: m/z 257.3 (M+1), 2: 257.3 (M+1), 3: 271.3 (M+1)이었다. 각 생성물질의 표지효율은 MEK에서 $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ $([^{11}C]1:[^{11}C]2:[^{11}C]3)$, CHO에서 $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$, DEK에서 $29.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$, DMF에서 $7.6{\pm}0.5%:0.0%:0.0%$이다. 결론: $[^{11}C]1$은 4가지 반응용매 중 MEK 반응용매에서 가장 높은 표지효율을 나타냈다. 부산물인 $[^{11}C]3$은 고성능 액체 크로마토그래피의 자외선, 방사능 검출기와 질량 분석법을 통해 물질을 추정할 수 있었다.의 개선 효과가 있는 것으로 판단되며 지질과산화에 대해서 강한 억제 활성을 나타내는 것을 알 수 있었다. 이러한 결과로 복분자는 생활 습관병의 예방과 개선에 유효한 것으로 사료되었으며, 지질대사와 과산화지표의 검증을 통해 기능성 식품소재로 활용될 수 있음을 보여주었다.로서 역시 CTV 치료계획에서 적게 조사되었다(p=0.005). 기존의 ICRU 치료계획은 잔류종양의 크기가 작은 경우 불필요하게 정상조직에 많은 선량이 투여되기 때문에 CT를 이용한 CTV 치료계획을 적용하여 정상조직에 대한 피폭을 현저히 낮추고 잔류종양에 목표한 선량을 조사할 수 있다.

• 동의생리병리학회지
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• 제17권1호
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• pp.1-24
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• 2003

This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.