• 제목/요약/키워드: Target repositioning

검색결과 22건 처리시간 0.025초

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

  • Lee, Boah;Park, Seung Ju;Lee, Seulgi;Park, Seung Eun;Lee, Eunhye;Song, Ji-Joon;Byun, Youngjoo;Kim, Seyun
    • Molecules and Cells
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    • 제43권3호
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    • pp.222-227
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    • 2020
  • Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

모바일 조작 작업을 위한 역접근성 기반의 효율적인 베이스 재배치 방법 (Efficient Base Repositioning for Mobile Manipulation based on Inverse Reachability)

  • 정홍렬;전정민;프란시스코윰블라;문형필
    • 로봇학회논문지
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    • 제16권4호
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    • pp.313-318
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    • 2021
  • This paper proposes a new method to generate inverse reachability maps that are more efficient for mobile manipulators than the previous algorithms. The base positioning is important to perform the given tasks. Using the inverse reachability method, we can know where to place the robot's base for given tasks. For example, the robot successfully performed the task with relocation, even when the target is initially in a low manipulability area or outside the workspace. However, there are some inefficiencies in the online process of the classical inverse reachability method. We describe what inefficiencies appear in the online phase and how to change the offline process to make the online efficient. Moreover, we demonstrate that the proposed approach achieves better performance than usual inverse reachability approaches for mobile manipulation. Finally, we discuss the limitations and advantages of the proposed method.

Study on The Development of A New Whole Body Fame

  • Chung, Jin-Bum;Suh, Tae-Suk;Chung, Won-Kyun;Choe, Bo-Young;Lee, Hyoung-Koo
    • 한국의학물리학회:학술대회논문집
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    • 한국의학물리학회 2002년도 Proceedings
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    • pp.136-137
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    • 2002
  • We have been researching upgrade version of a stereotactic whole body frame, used for evaluating daily setup accuracy of the patient positioning during fractionated extra-cranial stereotactic radiotherapy. Currently, we are focusing on the development of a new stereotactic whole body frame, and then will handle organ movement produced by breathing at the next stage. MeV-Green is chosen for the best immobilizer possible and the epoxy board is for the frame with the dimension of 110 em in length, 50 cm in width in order to maximize transmission rate of the beam from lateral or posterior direction and to fit CT and PET scanners with an aperture of 55 cm at least. The key point of an upgraded stereotactic whole body frame will be set on the collision-free rotation of the gantry with the frame, and the development of the checking structure for the daily patient repositioning regarding internal target.

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백화점(百貨店) 및 브랜드의 마케팅전략(戰略) 제안(提案)을 위한(爲限) 영캐주얼 브랜드의 위치(位置) 분석(分析) - L 백화점(百貨店)을 중심(中心)으로 - (A Study on the Position of Young Casual brands to Propose Marketing Strategies of the Brands and those of the Department Stores - focused on the L-Department Store -)

  • 유지헌
    • 패션비즈니스
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    • 제8권4호
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    • pp.117-130
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    • 2004
  • The purposes of this study were to find out highly market sharing young casual brands, to compare their trends of concept and competition, and to propose orientation of brand concept repositioning and marketing strategies on Department stores. Reference searching method and field searching method were used for this study. The results were as follows: 1. The brands which covered more than 50% market share included <96NY> . 2. Price range of these brands was from 130,000 to 220,000 won. The brands of upper-moderate price zone included <96NY> and they were very competitive each other. The brands of moderate price zone included and they were also very competitive between them. However, the brands of lower-moderate price zone had lower competition. This price zone might be a good point to launch new brands. 3. The main target-age of young casual zone was from 17 to 30 years. The most of brands focused on 21-25 years old, which were higher age targeted before. 4. The main concepts of these brands were 'luxury, girlish, sexy' and 'Sportism, lifestyle' were sub-concepts.

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells

  • Sung, So Jung;Kim, Hyun-Kyung;Hong, Yong-Kil;Joe, Young Ae
    • Biomolecules & Therapeutics
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    • 제27권1호
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    • pp.117-125
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    • 2019
  • Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

Identification of druggable genes for multiple myeloma based on genomic information

  • Rahmat Dani Satria;Lalu Muhammad Irham;Wirawan Adikusuma;Anisa Nova Puspitaningrum;Arief Rahman Afief;Riat El Khair;Abdi Wira Septama
    • Genomics & Informatics
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    • 제21권3호
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    • pp.31.1-31.8
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    • 2023
  • Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.

척추방사선수술시 실시간 추적검사에 의한 병소목표점 위치변이 평가 (Evaluation of Real-time Target Positioning Accuracy in Spinal Radiosurgery)

  • 이동준
    • 한국의학물리학회지:의학물리
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    • 제24권4호
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    • pp.290-294
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    • 2013
  • 방사선수술은 고 용량의 방사선을 병소의 목표점에 정확하게 주위의 정상조직을 보호하면서 한 번에 혹은 수 차에 거쳐 전달하는 방법이므로 병소 국재에 대한 오차의 크기는 방사선수술에 직접적인 영향을 끼치게 된다. 본 연구에서는 영상유도 국재 장비인 ExacTrac (BrainLab, Germany)을 이용한 척추방사선수술에서 병소 목표점 국재의 오차를 평가하였다. 국재 오차를 최소화 하기위하여 방사선수술 전 '환자위치 확인장치(PPVT)'를 고안하여 부가적으로 사용하였다. 실시간 목표점오차 평가를 위하여 흉추에 전이된 종양에 대한 방사선수술 8례를 대상으로 평가하였다. 그 결과 isocenter 목표점 오차는 횡단면(lateral) 축 방향, 종단면(longitudinal) 축 방향, 수직면(vertical) 축 방향으로 각각 $0.07{\pm}0.17$ mm, $0.11{\pm}0.18$ mm, $0.13{\pm}0.26$ mm이었으며 평균 공간오차는 $0.20{\pm}0.37$ mm이었다. 병소 isocenter의 회전오차(body rotation)는 종단면(longitudinal) 축 방향 $0.14{\pm}0.07^{\circ}$, 횡단면(lateral) 축 방향 $0.11{\pm}0.07^{\circ}$, 환자테이블 각 이동 $0.03{\pm}0.04^{\circ}$로 평균오차는 $0.20{\pm}0.11^{\circ}$이었다. 본 연구결과 영상유도 국재방법을 이용한 척추방사선수술에서의 병소목표점 국재 평균오차는 임상적으로 허용할 수 있는 오차범위 이내 임을 확인하였다.

Deep Learning for Herbal Medicine Image Recognition: Case Study on Four-herb Product

  • Shin, Kyungseop;Lee, Taegyeom;Kim, Jinseong;Jun, Jaesung;Kim, Kyeong-Geun;Kim, Dongyeon;Kim, Dongwoo;Kim, Se Hee;Lee, Eun Jun;Hyun, Okpyung;Leem, Kang-Hyun;Kim, Wonnam
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2019년도 추계학술대회
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    • pp.87-87
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    • 2019
  • The consumption of herbal medicine and related products (herbal products) have increased in South Korea. At the same time the quality, safety, and efficacy of herbal products is being raised. Currently, the herbal products are standardized and controlled according to the requirements of the Korean Pharmacopoeia, the National Institute of Health and the Ministry of Public Health and Social Affairs. The validation of herbal products and their medicinal component is important, since many of these herbal products are composed of two or more medicinal plants. However, there are no tools to support the validation process. Interest in deep learning has exploded over the past decade, for herbal medicine using algorithms to achieve herb recognition, symptom related target prediction, and drug repositioning have been reported. In this study, individual images of four herbs (Panax ginseng C.A. Meyer, Atractylodes macrocephala Koidz, Poria cocos Wolf, Glycyrrhiza uralensis Fischer), actually sold in the market, were achieved. Certain image preprocessing steps such as noise reduction and resize were formatted. After the features are optimized, we applied GoogLeNet_Inception v4 model for herb image recognition. Experimental results show that our method achieved test accuracy of 95%. However, there are two limitations in the current study. Firstly, due to the relatively small data collection (100 images), the training loss is much lower than validation loss which possess overfitting problem. Secondly, herbal products are mostly in a mixture, the applied method cannot be reliable to detect a single herb from a mixture. Thus, further large data collection and improved object detection is needed for better classification.

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전립선암에 대한 초음파 영상유도 방사선치료의 Setup 오차 분석을 통한 재현성 평가 (Reproducibiity of setup error for prostate cancer by ultrasound image-guided radiation therapy)

  • 박성용;임승규;시명근;이지해;김종열;조은주
    • 대한방사선치료학회지
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    • 제29권2호
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    • pp.75-81
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    • 2017
  • 목 적: 전립선암 환자에 대한 비침습적이고 피폭선량에 대한 부담이 없는 초음파를 이용한 영상유도방사선치료의 Setup 오차 분석을 통해 치료의 재현성을 평가해 보고자 한다. 대상 및 방법: 치료가 종료된 전립선암 환자 26명의 1,105영상에 대하여 앞-뒤(anterior-posterior, AP), 좌-우(right-left, RL), 위-아래(superior-inferior, SI) 방향의 Setup 오차에 대해 평균, 표준편차와 3D-error을 분석하였다. 또한 오차범위 0-1 mm, 1-3 mm, 3-5 mm, 5 mm 이상에 대한 각 오차 빈도수(frequency, %) 분석을 통하여 AP, RL, SI 방향에 대한 방향성을 확인 하였다. 결 과: Setup 오차는 AP, RL, SI 방향에 대하여 평균과 표준편차는 $1.87{\pm}1.36mm$, $1.73{\pm}1.22mm$, $2.01{\pm}1.40mm$였다. 3D-error는 평균 $3.63{\pm}1.63mm$였다. 각 방향에 대한 Setup 오차값의 빈도(frequency, %)는 AP 방향에 대한 오차범위 0-1 mm에서 29 %, 1-3 mm에서 50.2 %, 3-5 mm에서 19.6 %, 5 mm 이상에서 1.3 %였다. RL 방향에 대하여 오차범위 0-1 mm에서 31.3 %, 1-3 mm에서는 52.5 %, 3-5 mm에서는 15.8 %, 5 mm 이상에서 0.5 %였다. 마지막으로 SI 방향에 대한 오차범위 0-1 mm에서 26.3 %, 1-3 mm에서 50.2 %, 3-5 mm에서 22.4 %, 5 mm 이상에서 1.1 %였다. 결 론: Setup error는 SI 방향에서 $2.01{\pm}1.40mm$로 가장 컸으며 오차 빈도는 모든 방향에서 50 % 이상 오차 범위 1-3 mm에 들어온 것으로 확인되었다. $Clarity^{TM}$ Auto scan을 이용한 초음파영상유도 방사선치료는 치료 전에 방광의 전처치 상태, target의 구조 등을 관찰이 가능하고, 치료 중 target의 움직임을 실시간으로 monitoring하여 빠른 repositioning이 가능하다. 결과적으로 초음파를 이용한 실시간 영상유도방사선치료는 치료의 재현성을 높일 수 있을 것으로 사료된다.

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분할 정위방사선 치료 시스템 개발 연구 (Development of A Fractionated Stereotactic Radiotherapy System)

  • 이동한;지영훈;이동훈;조철구;김미숙;유형준;류성렬
    • 한국의학물리학회지:의학물리
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    • 제13권1호
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    • pp.9-14
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    • 2002
  • 두부 프레임을 지지하는 방식으로 pedestal mounting system과 couch mounting system의 장점을 수용한, 새로운 형태의 분할 정위방사선 치료 시스템을 개발하였다. 두부 고정을 위한 프레임은 두랄루민으로 제작하였고, 카우치에 부착되게 하였다. 프레임 내에서 환자의 두부를 고정하기 위해 치아 고정장치와 3.2 mm 열프라스틱으로 전두부와 후두부에 마스크를 제작할 수 있다. 정위 좌표 구현을 위한 전산화 단층촬영 localizer는 각 병원에서 많이 사용하고 있는 Brown-Roberts-Walls(B.R.W) 시스템을 사용할 수 있게 하여, 개발된 시스템의 신뢰성을 높이고 제작 단가도 낮추고자 하였다. 프레임 mounting system은 pedestal mounting system을 수정, 보완한 형태로 개발하였다. 시스템은 카우치를 지지하는 바닥 면에 고정되어 카우치에 부착된 프레임과 결합할 수 있고, 시스템과 카우치의 잠금 장치를 푼 채 자유롭게 x, y축으로 유동할 수 있다. 프레임 mounting system의 중심축은 상, 하 방향으로 이동 가능한 포인터 형태로 제작하여, 치료기의 구동 정확성을 검증하는 정도 관리에 응용 가능하다. 개발된 시스템의 재현성과 정확도 검증을 위해 아크릴 팬텀과 포인터를 제작하였고, 전산화 단층촬영 영상에서 획득한 팬텀 내 목표점의 정위 좌표를 dial-gauge와 E.C.L 필름으로 검증하였다. 실험의 결과 x축 방향의 재현성 오차는 0.71$\pm$0.19 mm, y축 방향은 0.45$\pm$0.15 mm, z축 방향 재현성 오차는 0.63$\pm$0.18 mm로 나타났고, 최대 1.3 mm 이내의 우수한 재현성을 보였다. 연구 결과로 개발된 분할 정위방사선 치료 시스템은 재현성이 우수하고, 전체 중량이 가벼워 사용하기 쉽게 제작되었다. 특히 수정된 pedestal frame mounting system으로 설계되어 후두부 방사선 조사가 가능한 장점이 있다.

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