• Title/Summary/Keyword: 약물 표적

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Preparation of Novel Natural Polymer-based Magnetic Hydrogels Reinforced with Hyperbranched Polyglycerol (HPG) Responsible for Enhanced Mechanical Properties (과분지 폴리글리세롤(HPG) 강화를 통해 기계적 물성이 향상된 새로운 천연 고분자 기반 자성 하이드로젤의 제조)

  • Eun-Hye Jang;Jisu Jang;Sehyun Kwon;Jeon-Hyun Park;Yujeong Jeong;Sungwook Chung
    • Clean Technology
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    • v.29 no.1
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    • pp.10-21
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    • 2023
  • Hydrogels that are made of natural polymer-based double networks have excellent biocompatibility, low cytotoxicity, and high water content, assuring that the material has the properties required for a variety of biomedical applications. However, hydrogels also have limitations due to their relatively weak mechanical properties. In this study, hydrogels based on an alginate di-aldehyde (ADA) and gelatin (Gel) double network that is reinforced with additional hydrogen bonds formed between the hydroxyl (-OH) groups of the hyperbranched polymer (HPG) and the functional groups present inside of the hydrogels were successfully synthesized. The enhanced mechanical properties of these synthesized hydrogels were evaluated by varying the amount of HPG added during the hydrogel synthesis from 0 to 25%. In addition, magnetite nanoparticles (Fe3O4 NPs) were synthesized within the hydrogels and the structures and the magnetic properties of the hydrogels were also characterized. The hydrogels that contained 15% HPG and Fe3O4 NPs exhibited superparamagnetic behaviors with a saturation magnetization value of 3.8 emu g-1. These particular hydrogels also had strengthened mechanical properties with a maximum compressive stress of 1.1 MPa at a strain of 67.4%. Magnetic hydrogels made with natural polymer-based double networks provide improved mechanical properties and have a significant potential for drug delivery and biomaterial application.

Bidirectional Cross-talk Between Estrogen Receptor and Growth Factor Receptors in Breast Cancer Cell (유방암세포에서 에스트로겐 수용체와 성장인자 수용체 사이의 양방향 상호작용)

  • Min, Gyesik
    • Journal of Life Science
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    • v.28 no.2
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    • pp.265-273
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    • 2018
  • Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

Radiosurgery with Linac Based Photon Knife in Cerebral Arteriovenous Malformation (선형가속기를 이용한 Photon Knife 방사선수술에 의한 뇌동정맥기형의 치료)

  • Kim, Jin-Hee;Choi, Tae-Jin
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.1-9
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    • 2003
  • Purpose : The purpose of this study was to analyze the effect of a Linear accelerator based Photon Knife Radiosurgery System developed by the staff of Keimyung University Dongsan Medical Center for the treatment of cerebral arterlovenous malformation Material and Methods : Between December 1993 and October 2000, 30 patients with cerebral arteriovenous malformation (AVM) were treated with the Linac based Photon knife Radlosurgery System In the Department of Therapeutlc Radiology at Keimyung University Dongsan Medical Center. The median age was 34, ranging from 7 to 63 years, with a 2 : 1 male to female ratio. The locations of the AVM nidi were the frontal lobe (motor cortex), parletal lobe, and the thalamus, In that order. The diameters of the AVM nidi ranged 1.2 to 5.5 cm with a mean on 2.9 cm, and target volumes of between 0.5 and 20.5 cc, with a mean of 5.8 cc. The majority of patients received radiation doses of between 1,500 and 2,500 cGy, w14h a mean of 2,000 cGy, at 80% the isodose line. Twenty-five patients were treated with one isocenter, 4 with two, and 1 with four. The follow-up radiological evaluations were peformed with cranial computed tomogram (CT) or MRI between 6 month and one year interval, and if the AVM nidus had completely disappeared in the CT or MRI, we confirmed thls was a complete obliteration, with a cerebral or magnetic resonance angiogram (MRA). The median iollow-up period was 39 months with a range of 10 to 103 months. Results : Twenty patients were radloiogicaiiy followed up ior over 20 months, with complete obliteration observed in 14 (70%). According to the maximal diameter, all four of the small AVM (<2 cm) completely obliterated, 8 of the 10 patients with a medium AVW (2~3 cm) showed a complete obliteration, and two showed partial obliteration. Among the patients with a large AVM (>3 cm), only one showed complete obliteration, and S showed partial obliteration, but 3 oT these underwent further radiosurgery 3 years later. One who followed up for 20 months fellowing further radiosurgery eventually showed complete obliteration. Ten patients with seizure symptoms had no recurrent seizure due to radiosurgery and medication. One of the eleven patients who suffered intracranlal bleeding developed further bleeding at 9 and 51 months fellowing the radiosurgery although complete obliteration was eventually observed and the patient was managed in hospital then recovered. No patient suffered severe complications fellowing the radiosurgery. Conclusion : The radiosurgery with Linac-based Photon knife radiosurgery system, developed by the staff at our hospital, is a safe and effective treatment for AVM patients having diameters or volumes of less than 3 cm or 10 cm$^{3}$, respectively, located In Inoperable areas or who refused neurosurgery. We suggest that staged AVM radiosurgery may initially be considered, if the AVM target volume is above 10 cm$^{3}$

Effect of Ethane 1,2-Dimethane Sulfonate(EDS) on the Expression of Steroid Hormone Receptors, $5{\alpha}$-reductase and Aromatase in the Rat Epididymis (흰쥐 부정소 내의 스테로이드 호르몬 수용체, $5{\alpha}$-reductase 그리고 Aromatase 발현에 미치는 EDS의 영향)

  • Son, Hyeok-Joon;Lee, Sung-Ho
    • Development and Reproduction
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    • v.11 no.3
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    • pp.187-193
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    • 2007
  • Ethane 1,2-dimethane sulfonate(EDS), a Leydig cell specific toxicant, has been widely used to create the reversible testosterone withdrawal rat model. Though the maintenance of epididymal structure and function is highly dependent on the testosterone secreted from testis, its derivatives, dihydroxytestosterone(DHT) and estrogen, might have crucial roles. The aim of present study was to monitor the expression patterns of sex steroid receptors, cytochrome P450 aromatase(P450arom) and $5{\alpha}$-reductase in the rat epididymis up to 7 weeks after EDS injection. Adult male rats($350{\sim}400g$) were injected with a single does of EDS(75 mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. The transcriptional activities of the target genes were evaluated by semi-quantitative RT-PCRs. The transcript level of estrogen receptor alpha($ER{\alpha}$) in EDS group was significantly higher than control level on week 1(P<0.01). After week 2, there was no significant difference in $ER{\alpha}$ levels between EDS group and control. The transcript level of estrogen receptor beta($ER{\beta}$) in EDS group was significantly higher than control level on week 1(P<0.05), lowered on weeks 2 and 3(P<0.05 and P<0.01, respectively), fluctuated during weeks 4 and 6, and elevated on week 7(P<0.05). The androgen receptor (AR) message levels increased significantly week 2(P<0.01), then returned to control level on week 3. In contrast, expression of cytochrome P450 aromatase(P450arom) decreased sharply during weeks $1{\sim}3$(P<0.01 on weeks 1 and 2; P<0.05 on week 3), then went back to control level on week 4. The mRNA level of $5{\alpha}$-reductase type 2($5{\alpha}$-RT2) increased significantly on week 4(P<0.01), then returned to control level. The present study indicated that EDS administration could induce reversible alterations in the transcriptional activities of sex steroid hormone receptors and androgenconverting enzymes in rat epididymis. EDS injection model will be useful to clarify the regulation mechanism of mammalian epididymal physiology.

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MicroRNA-23b is a Potential Tumor Suppressor in Diffuse Large B-cell Lymphoma (미만성 거대 B 세포 림프종(DLBCL)에서 microRNA-23b의 잠재적 종양 억제자로서의 효과)

  • Nam, Jehyun;Kim, Eunkyung;Kim, Jinyoung;Jeong, Dawoom;Kim, Donguk;Kwak, Bomi;Kim, Sang-Woo
    • Journal of Life Science
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    • v.27 no.2
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    • pp.149-154
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    • 2017
  • Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment (에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -)

  • Lee, So Hee;Oh, Dong-Yul;Han, Jin-Hee;Choi, Ihn-Geun;Jeon, Yang-Whan;Lee, Joon-Noh;Lee, Tae Kyung;Jeong, Jong-Hyun;Jung, Kyung Hwa;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.115-121
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    • 2007
  • Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

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Cytotoxic Effect and Protein Expression by Korean Regional Propolis on HeLa Ovarian Cancer Cell Line (HeLa 암세포주에 대한 국산 프로폴리스의 독성 효과 및 단백질 발현 변화)

  • Kim, Sung-Kuk;Woo, Soon Ok;Han, Sang Mi;Kim, Se Gun;Bang, Kyung Won;Kim, Hyo Young;Choi, Hong Min;Moon, Hyo Jung
    • Journal of Apiculture
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    • v.34 no.3
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    • pp.245-254
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    • 2019
  • We investigated the anti-tumor effects and molecular mechanism of Brazil, China and Korean regional propolis on HeLa ovarian cancer cell line. Each propolis extracts was prepared by ethanol extraction method. Cytotoxicity of propolis extracts was determinated by EZ-cytox cell viability assay. To necessity of anti-tumor effect and molecular mechanism of propolis, we must be adjusting propolis concentration. Due to 100 ㎍/mL of propolis extract were reduced cell viability to less than 50%, we adjusted all of propolis concentration to 100 ㎍/mL. By Western blotting analysis, we confirmed that anti-tumor mechanism of Brazil, China and Korea regional propolis has significantly difference. All of propolis was activated apoptosis related molecules such as PARP, caspase-3. However, cell proliferation signaling molecules including Akt1, ERK and Bcl-2 were reduced the protein expression level. Especially, the expression of tumor suppressor protein p53 was significantly increased in propolis-treated group such as Gyeonggi, Chungbuk, Chungnam, Jeonbuk, Gyeongnam and China. The phosphorylation of Bax which as apoptosis indicator was appeared in propolis-treated group such as Gyeonggi, Gangwon, Chungnam, Gyeongbuk, China. In this results showed that the regional propolis has completely different mechanism in anti-tumor. Thus, propolis extracts may be useful source of functional materials on anti-cancer and it will be able to choose the suitable propolis for cancer therapy by analyzing individual characteristics.

Health Promotion Through Healthy People 2010 ("2010년대 건강한 시민" 정책을 통한 미국의 건강증진 방향)

  • Cho, Jung H.
    • Proceedings of The Korean Society of Health Promotion Conference
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    • 2004.10a
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    • pp.17-58
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    • 2004
  • 뉴저지주 보건교육/건강 증진정책을 논하기전에 건강증진과 보건 교육사의 뜻을 먼저 기술하기로 한다. 건강증진이란 일상 사회생활과 행동과학의 응용에서 시작하며 교육의 효율적 작전 및 기술, 질병 역학 조사, 개인 및 가족단위 건강 위해 행위 절감, 사회연관 구축망 조성, 그리고 적게는 이웃, 더 나아가 조직체계 및 지역 사회의 네트웍 실시등을 실시한다. 보건교육 및 건강증진 전문가란 ' 전국 보건교육 인증 위원회(NCHEC) ' 에서 채택된 다음 7개 활동 영역에서 개인적, 그룹, 각주단위, 그리고 범 국가적 조직에서 종사하는자로 한다. 개인 및 지역사회 보건 교육 필요성 분석- 계회, 실행, 효율성 평가, 사업 진행 조정, 자문, 컴뮤니케이션 등의 활동범위를 들 수 있다. 공인 보건 교육사(CHES)란 대학 및 대학원에서 보건 교육학 소정의 필수 과목을 이수하고 학.석사 소지자로서 ' 전국 보건 교육 인증 위원회 ' 에서 그 자격을 인정 받고 공인 자격 시험에 합격한자로 한다. 합격자는 자기 성명뒤에 CHES란 칭호를 부치며 매 5년마다 75단위이상 인정된 전문 직업 보수 교육을 받아야 한다. 보건 교육사 고용 분야는 연방, 주, 지방 정부의 보건 교육사(10-15%) 및 건강 증진 전문가로 종사하며; 이들은 지역 사회 조직화, 프로그람 기획, 공공사업 마켓팅, 메디아, 컴뮤니케이션 자질을 갓추어야 하며; 상해 예방, 학교 보건, 지역 사회 영양 실태 향상, 그 외 모든 건강 증진과 질병 예방에 일익을 담당 하여; 의사, 간호사, 약사, 영양사,환경 위생사드의 전문분야종사자들괴 한팀이 되어 지역 사회 보건 사업에 기여한다. 쥬저지 보건 교육사들은 주법령 8조 '||'&'||' 보건행정 표준 시행령 ' 에 따라 포괄적 보건교육/건강증진 프로그램을 개발하여 총체적으로 조절 관장한다. 특희 ' 미국 학술원 의료 연구원 ' 에서 제정한 ' 10대 필수 공중 보건 사업 ' 에 기준을 두고; 1) 개인 및 지역사회 필수 보건 여건 분석 평가, 2) 보건 교육 이론에 따른 사업 계획 설정, 3) 교육 전략과 보건문제 발굴에 따라 일반 대중 대상 보건 교육 실행 (프로그람 기획, 연수 교육, 미디어 캠페인, 공중보건 향상책 옹호), 4) 사업 진행 과정 정리, 그 결과에 대한 영향력과 결과 평가, 5) 프로그램진행, 인사 및 예산관리 참여, 6) 근무향상을 위한 보수교육 프로그램 개발, 7) 보건 의료 업무 종사자 상호 협조성 향상 훈련, 8) 지역 사회자원 밭굴, 9) 적절한 고객 의뢰 체제 시행, 10) 위기 관리 컴뮤니케이션 체제 개발실시, 11) 일반 대중에게 공중 보건 향상 고취, 12) 각종 협력 지원금 신청서 작성 제출, 13) 문화/인종적으로 적절한 시청각 교재 발굴, 15) 질적 및 양적 보건교육/건겅증진책 연구 실시, 16) 비 보험 가담자, 저 보험자, 빈곤자, 이민자 색출 선도, 17) 관활 구역내 상재하는 각 건강증진 프로그램 밝혀 내서 불필요한 중복 회피등이다. 그 외에도 보건 교육사들은 사회 복지 단체인 미국 암 협회, 미국 심장 협회,미국 폐장 협회 등 각종 사회 복지 비영리단체 와 자선 사업 단체들과 긴밀희 협조하거나 그 단체 임직원으로서 건강 증진 사업에 종사한다. 병원 및 의료기관에선 임직원 보수 교육, 환자의 질병 예방및 건강증진 교육, 그리고 의료 사업장내 건장 증진업무에 종사한다. 건강 유지 의료 기관(HMO)에선 예방주사, 정기검진 촉진등을 통한 입원일수 절감, 응급실 사용도 절감등으로 의료비 감축, 삶의질 향상상에 종사한다. 사업장 보건 교육사는 스트레스 관리, 금연 및 흡연 중단선도, 체중 절감, 종업원 건강증진 생활화참여 유치, 컴뮤니케이션 개발, 마켓팅, 질병 예방등에 그 전문 직업적 노하우를 사업체 건강 증진 프로그램 개발에 접목한다. 뉴저지 2010년대 건강 증진책은 5대 목표 설정하여 현재 시행하고 있다. 특이한점은 2001년 9.11사태 이후 연방정부와 주정부의 상당한 예산 지원을 그랜트 지원금 형식으로 받아 연방, 주정부, 지방 정부, 의료 기관등에서 일사 불란하게 생물/화학/방사성 테러에 대비하는데 보건 교육사들은 시민 인지도 향상과 위기관리 컴뮤니케이션 영역에서 활약한다. 총체적인 보건 교육/건강 증진책은 다음 천년간 뉴저지 건강증진 백서와 미연방 정부 건강증진 2010에 준하여 설립한 뉴저지 건강 증진 2010 에 의한다. 그 모델을 보면; 1) 생활 습관 향상으로 위해 행위 절제; 적절한 영양 섭취 와 과체중화 차단 불필요한 투약 절제와 그 관리 흡연 탐익 절감, 금연, 흡연관련 신체/정신적 피해 관리/치료 습관성 약물 중독 조기발견 예방 낙상 예방 폭력, 의도적/비의도적 상해 예방 2) 심장질환, 암, 뇌졸중, 당뇨, 폐염, 인프루엔자등 주사망원인 질병 조기 발견 예방 책 마련; 독감.폐렴 예방 주사 실시 3) 보건 교육 대상과 표적 설정 특히 보건사업 참여 동반자 발굴하여 그 동참과 책임분담 책려; 주. 지방 정부기관, 의료 종사자, 의료 보험 업자, 대학 등 교육 기관, 연구 기관, 교육자, 지방 보건소, 지역 사회 비 영리단체, 종교 단체 및 교역자 등의 참여 촉구., 지역 사회 비 영리단체, 종교 단체 및 교역자 등의 참여 촉구.

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