• Title/Summary/Keyword: 약물 표적

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Rare Disease Research and Orphan Drug Development (희귀질환 연구와 치료제 개발 동향)

  • Lee, Shinhaeng;Lee, Jangik I.
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.1
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    • pp.1-13
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    • 2013
  • 희귀질환이란 일반적으로 그 유병율이 인구 일만 명당 5명 이하인 질환을 말한다. 세계에는 약 7,000여종의 희귀질환이 알려져 있고 학술지에 매 주 대략 5종의 새로운 희귀질환이 보고되고 있다. 희귀 의약품(orphan drug)이란 희귀질환치료제 또는 수익성이 없어 개발을 기피하는 일반질환 치료제로서 정부가 지정한 의약품을 말한다. Orphan 의약품의 개발에는 많은 장점이 있다. Orphan 의약품으로 정부의 지정을 받으면 세금감면을 통한 연구비 지원, 임상시험 비용 지원, 신약허가 심사비 면제, 시장독점권 부여 등의 특혜가 주어진다. 희귀질환의 대부분은 단순한 유전적 결함에 의하는 경우가 많아 치료제의 표적발견이 비교적 쉬우므로 개발 성공률이 높고, 임상시험기간이 짧으며, 시판허가를 받을 확률이 높아 연구개발비용이 적게 든다. 그 결과 전세계 orphan 의약품 시장은 최근 매년 6%씩 성장하여 2014년에는 약 1,120억달러의 시장을 형성할 것으로 추정된다. Orphan 의약품 시장은 현재 매년 8.9%씩 성장하고 글로벌 시장의 51%를 점유하는 미국을 중심으로 확장되어 가고 있으며, 총매출액의 64.3%가 유전자재조합의약품에 의한 것으로 알려져 있다. 이러한 의약품시장의 변화와 사회적 요구에 부응하여 한국 또한 희귀질환 치료제 개발의 활성화를 위해 재정적 지원체계를 구축하고, 허가관리를 개선하며, 법률적 제도를 완비하는 과정에 있다. 현재 희귀질환의 치료적 타겟을 찾아 신물질이나 기존의 약물을 발굴하는 과정이 주로 대학이나 연구 중심 병원에서 이루어지고 있다. 제도가 잘 정립되어 있는 미국 시장을 겨낭하여 orphan 의약품 개발을 전략적으로 수행한다면 큰 성공을 거둘 수 있을 것으로 기대된다.

Fabrication of Fluorescent Labeled Bi-compartmental Particles via the Micromolding Method (미세 성형 방법을 이용한 형광 표지된 이중 분획 입자의 제조)

  • Shim, Gyurak;Jeong, Seong-Geun;Hong, Woogyeong;Kang, Koung-Ku;Lee, Chang-Soo
    • Korean Chemical Engineering Research
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    • v.56 no.6
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    • pp.826-831
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    • 2018
  • This study presents fabrication of bi-compartmental particles labeled by multiple fluorescence. To compartmentalize fluorescent expression at the particle, two fluorescent dyes with less overlap of the excitation and emission spectra are selected. To ensure the fluorescence stability, the fluorescent dyes contain acrylate functional groups in the molecules so that they can be cross-linked together with monomers constituting the particle. Strong fluorescent expression and compartmentalization were observed at the particle fabricated using the selected fluorescent dyes through confocal microscopy. Furthermore, long-term fluorescence stability was verified by measuring fluorescent expression and intensity for 4 weeks. We anticipate that the bi-compartmental particles labeled by multiple fluorescence can be widely used for multi-target drug delivery system, analysis of 3 dimensional Brownian motion, and investigation of 3 dimensional complex self-assembled morphologies.

Understanding centrosome amplification in cancer: A pathway toward precision-targeted cancer drug development (암의 중심체 증폭 이해를 통한 표적 항암제 개발)

  • Taekyung Kim
    • Journal of Life Science
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    • v.33 no.11
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    • pp.950-955
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    • 2023
  • Cell division is an essential process for the survival and development of living organisms. It is critical that duplicated chromosomes are properly segregated into daughter cells during mitosis. The centrosome is the core organelle that forms the microtubule-organizing center (MTOC), which generates the microtubules that make up the mitotic spindle during cell division. The centrosome is also involved in cell signaling and motility. In normal cells, there is one centrosome in G1 that replicates into two in the S phase and matures through G2. During the M phase, duplicated centrosomes move to both ends of the cell, and spindle microtubules that are generated from MTOC move the chromosome to both ends. The cells then split into two to complete the cell division. However, a phenomenon called centrosome amplification (CA), in which the number of centrosomes is higher than normal, is common in cancer cells and can lead to chromosome instability (CIN). This paper discusses the process of centrosome replication and the role of PLK4 in this process. The possible consequences of centrosome amplification and how the PLK4 inhibitor may be able to treat certain types of cancer cells, such as breast cancer and neuroblastoma, will also be discussed.

Clinical Outcomes and Prognosis of Patients with Stent Fracture after Successful Drug-Eluting Stent Implantation (관상동맥 약물 방출 스텐트 삽입 후 스텐트 골절에 대한 임상결과 및 예후)

  • Kim, In-Soo;Han, Jae-Bok;Jang, Seong-Joo
    • Journal of radiological science and technology
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    • v.37 no.2
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    • pp.109-116
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    • 2014
  • Many studies have suggested that in the era of Drug-Eluting Stents(DES) are one of the causes of In-Stent Restenosis(ISR) of Stent Fracture(SF). The present study sought to evaluate clinical characteristics of patients with stent fracture after successful DES implantation. The 4,701 patients were selected for analysis who underwent a follow-up coronary angiography irrespective of ischemic symptoms. The overall incidence of SF was 32 patients(male:female=19:13, Av. age $62.44{\pm}9.8$year, 0.68%). Fractures of Sirolimus-Eluting Stents(SES), Paclitaxel-Eluting Stents(PES), Biolimus A9-Eluting Stents(BES), Everolimus-Eluting Etents(EES), Endothelial Progenitor Cell Capture Stent(EPC) and Zotarolimus-Eluting Stents(ZES) are accounted for 19(59.4%), 9(28.1%), 2(6.3%), 1(3.1%), 1(3.1%) and 0(0%) respectively. SF developed in the left Anterior Dscending(LAD) artery in 16 patients(50%) and in complex(type B2, C) lesions in 25 patients(69.4%). Ten patients were treated with heterogenous DES, the rest being treated with either homogenous DES(3 patients), plain old balloon angioplasty(3 patients), or conservative medical treatment(17 patients). None of the patients with SF suffered from cardiac death during a follow-up period of $32.9{\pm}12.4$ months. The overall rate of DES fracture over up to 3.7 years of follow-up was 0.68% with higher incidence in SES than in PES. SF frequently occurred in the LAD artery and in complex lesions. Of the patients with SF, coronary intervention was performed only when the binary restenosis lesion was significant. During the follow-up, patients with SF have continued on combination antiplatelet therapy. There is a very low rate of major adverse cardiac events(post-detection of SF), especially cardiac death associated with SF.

The evaluation for Clinical usefulness and Safety of Sirolimus-eluting stent and Paclitaxel-Eluting Stents In Patients With Acute Myocardial Infarction (급성심근경색증 환자의 일차적 관동맥 스텐트 삽입술 시 삽입된 Sirolimus-eluting stent 와 Paclitaxel-eluting stent의 임상적 안정성 및 유용성 평가)

  • Min, Gye-Sik;Han, Man-Seok
    • Journal of the Korean Society of Radiology
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    • v.6 no.1
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    • pp.5-10
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    • 2012
  • There is a still unsettled issue about the comparison of long-term clinical effects between sirolimus-(SES) and paclitaxel-eluting stents (PES) for the patients with acute myocardial infarction (AMI). Therefore, we performed a retrospective analysis to evaluate the 4-year clinical outcome of SES as compared with PES after percutaneous coronary intervention (PCI) in patients with AMI. From January 2004 to August 2006, all consecutive patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI and acute NSTEMI underwent PCI by implantation either SES or PES were enrolled. The occurrence of death, cardiac death, recurrent infarction, target vessel revascularization (TVR) and stent thrombosis were analyzed. The composite of major adverse cardiac events (MACE; death, recurrent infarction and TVR) were also analyzed. During the study period, total 668 AMI patients had visited. Of them, total 522 patients (299 with SES and 223 with PES) were enrolled. During 4-year clinical follow-up, there were similar occurrences of death ($18.3{\pm}3.0%$ vs. $14.6{\pm}2.2%$, p=0.26), cardiac death ($11.2{\pm}2.6%$ vs. $6.8{\pm}1.52%$, p=0.39), re-infarction ($6.4{\pm}1.8%$ vs. $3.3{\pm}1.1%$, p=0.31), and stent thrombosis ($5.4{\pm}1.7%$ vs. $3.2{\pm}1.1%$, p=0.53) between the two groups, consecutively. The occurrences of TVR ($10.0{\pm}3.0%$ vs. $4.0{\pm}1.2%$, p=0.008) and MACE ($29.4{\pm}3.5%$ vs. $19.4{\pm}2.5%$, p=0.003) were significantly higher in patients treated with PES than SES. In AMI patients treated with either SES or PES implantation, SES had a significantly lower risk of TVR and MACE during 4-year clinical follow-up. Rates of death, cardiac death or recurrent infarction, and stent thrombosis were similar.

Experimental Studies on the Antitumor Effects of Jinryungtang Gagambang Extract (진령탕가감방의 항종양효과(抗腫瘍效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Jeong, Jun-Tak;Moon, Goo;Moon, Suk-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.37-53
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    • 1998
  • The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.

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The Study of Normal Tissue Complication Probability(NTCP) for Radiation Pneumonitis by Effective Volume Method (유효체적 방법과 임상분석을 통한 방사선에 의한 정상 폐조직의 부작용 확률에 관한 연구)

  • Ahn Seung Do;Choi Eun Kyung;Yi Byong Yong;Chang Hyesook
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.243-249
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    • 1997
  • Purpose : In radiation therapy, NTCF is very importart indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. Materials and Methods : From August 1993 to December 1994, thirty six patients with locally advanced non=small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutlc agents were mitomycin C. vinblastion, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of raniation pneumonitis by CT scan, chest x-rar and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumanitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung, Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. Results : Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients , 6 had grade I severity and 2 had grade II. The average NTCP value cf the patients who showed radiation pneumonitis was significantly higher than that uf the patients without pneumonitis $(66\%\;vs.\;26.4\%)$. But the results of pulmonary function test was not correlated with NTCP. Conclusion : NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to anaiyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.

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Potential Importance of Proteomics in Research of Reproductive Biology (생식생물학에세 프로테오믹스의 응용)

  • Kim Ho-Seung;Yoon Yong-Dal
    • Development and Reproduction
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    • v.8 no.1
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    • pp.1-9
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    • 2004
  • The potential importance of proteomic approaches has been clearly demonstrated in other fields of human medical research, including liver and heart disease and certain forms of cancer. However, reproductive researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity, and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis(2DE) and MALDI-TOF(matrix-assisted laser desorption ionization-time of flight) MS(mass spectrometry) or protein chip array and SELDI-TOF(surface-enhanced laser desorption ionization-time of flight) MS. In addition understanding the possessing knowledge of the developing biomarkers used to assess reproductive biology will also be essential components relevant to the topic of reproduction. The continued integration of proteomic and genomic data will have a fundamental impact on our understanding of the normal functioning of cells and organisms and will give insights into complex cellular processes and disease and provides new opportunities for the development of diagnostics and therapeutics. The challenge to researchers in the field of reproduction is to harness this new technology as well as others that are available to a greater extent than at present as they have considerable potential to greatly improve our understanding of the molecular aspects of reproduction both in health and disease.

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Effect of the Polaroid Lens in Binocular Vision (양안시에서 편광렌즈의 영향)

  • Kim, Douk-Hoon
    • Journal of Korean Ophthalmic Optics Society
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    • v.8 no.2
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    • pp.135-151
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    • 2003
  • This study compared the effect of Polaroid$^{(R)}$ lenses on binocular vision by assessing visual acuity, stereopsis, and visual evoked potential(VEP), through Polaroid$^{(R)}$, CR 39 and sunglass lenses. The spectral absorptions of Polaroid$^{(R)}$, CR 39 and sunglass lenses were measured using a spectrophotometer (Hitachi. U-3501). The VEP were recorded by the Nicolet system. Thirty normal adult(fifteen males, fifteen females, mean=21.9 years, range=20 to 25) subjects were recorded. The subjects were provided a history including : general health, family health, medication, genetics, allergy and disease. All had normal or corrected to normal acuity with no history of visual disorders. Corrected visual acuity, colour vision and stereopsis were recorded for each subject monocularly and binocularly. Each test was repealed through the sunglass, CR 39, and Polaroid$^{(R)}$ lenses. Subjects viewed the VEP stimulus both monocularly and binocularly through the test lenses while the VEPs were recorded. The results suggest that the binocular visual acuity and stereoacuity is better than with monocular vision. On other hand, the analysis of VEP suggests that the amplitude of wave is smaller when the monocular eye receives the VEP stimulus compared with that when the binocular eye is stimulated by the VEP target with the sunglass, CR 39, and Polaroid$^{(R)}$ lens. But, the latency period of each eye was similar to results between the dominant eye and the non-dominant eye by the CR 39, sunglass, and polaroid lens. In conclusion, this study indicates that the binocular vision appears to be better through the brown Polaroid$^{(R)}$ lens than through the other test lenses.

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The Influence of the Sympathetic Nervous System on the Development and Progression of Cancer (교감신경계가 암의 발전과 진행에 미치는 영향)

  • Park, Shin-Hyung;Chi, Gyoo-Yong;Choi, Yung Hyun
    • Journal of Life Science
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    • v.28 no.1
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    • pp.116-129
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    • 2018
  • Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.