• 제목/요약/키워드: Receptor-based approach

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대장암 세포에서 5-FU(Fluorouracil)의 세포독성과 관련된 단백체 분석 (Proteomic Approach to the Cytotoxicity of 5-FU(Fluorouracil) in Colon Cancer Cells)

  • 이서영;송진수;노시훈;김근태;홍순선;김희준;권성원;박정일
    • 약학회지
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    • 제53권3호
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    • pp.145-150
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    • 2009
  • We evaluated cytotoxic effect based on the MTT assay and identified altered proteins in 5-FU(fluorouracil) treated HT29 cells using two-dimensional gel electrophoresis and MALDI-TOF/TOF-MS. As proteins inducing apoptosis, siah binding protein 1 and p47 protein isoform a were up-regulated and tumor protein translationally-controlled 1 was down-regulated by 5-FU treatment. And mannose 6 phosphate receptor binding protein 1 controls DNA mismatch repair system was increased. We suggest 5-FU promotes a cytotoxicity under the action of these proteins in colon cancer cells.

Artificial Intelligence in the Pathology of Gastric Cancer

  • Sangjoon Choi;Seokhwi Kim
    • Journal of Gastric Cancer
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    • 제23권3호
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    • pp.410-427
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    • 2023
  • Recent advances in artificial intelligence (AI) have provided novel tools for rapid and precise pathologic diagnosis. The introduction of digital pathology has enabled the acquisition of scanned slide images that are essential for the application of AI. The application of AI for improved pathologic diagnosis includes the error-free detection of potentially negligible lesions, such as a minute focus of metastatic tumor cells in lymph nodes, the accurate diagnosis of potentially controversial histologic findings, such as very well-differentiated carcinomas mimicking normal epithelial tissues, and the pathological subtyping of the cancers. Additionally, the utilization of AI algorithms enables the precise decision of the score of immunohistochemical markers for targeted therapies, such as human epidermal growth factor receptor 2 and programmed death-ligand 1. Studies have revealed that AI assistance can reduce the discordance of interpretation between pathologists and more accurately predict clinical outcomes. Several approaches have been employed to develop novel biomarkers from histologic images using AI. Moreover, AI-assisted analysis of the cancer microenvironment showed that the distribution of tumor-infiltrating lymphocytes was related to the response to the immune checkpoint inhibitor therapy, emphasizing its value as a biomarker. As numerous studies have demonstrated the significance of AI-assisted interpretation and biomarker development, the AI-based approach will advance diagnostic pathology.

약물부작용 감시를 위한 공통데이터모델 기반 임상데이터웨어하우스 구축 (Development and Lessons Learned of Clinical Data Warehouse based on Common Data Model for Drug Surveillance)

  • 노미정
    • 한국병원경영학회지
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    • 제28권3호
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    • pp.1-14
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    • 2023
  • Purposes: It is very important to establish a clinical data warehouse based on a common data model to offset the different data characteristics of each medical institution and for drug surveillance. This study attempted to establish a clinical data warehouse for Dankook university hospital for drug surveillance, and to derive the main items necessary for development. Methodology/Approach: This study extracted the electronic medical record data of Dankook university hospital tracked for 9 years from 2013 (2013.01.01. to 2021.12.31) to build a clinical data warehouse. The extracted data was converted into the Observational Medical Outcomes Partnership Common Data Model (Version 5.4). Data term mapping was performed using the electronic medical record data of Dankook university hospital and the standard term mapping guide. To verify the clinical data warehouse, the use of angiotensin receptor blockers and the incidence of liver toxicity were analyzed, and the results were compared with the analysis of hospital raw data. Findings: This study used a total of 670,933 data from electronic medical records for the Dankook university clinical data warehouse. Excluding the number of overlapping cases among the total number of cases, the target data was mapped into standard terms. Diagnosis (100% of total cases), drug (92.1%), and measurement (94.5%) were standardized. For treatment and surgery, the insurance EDI (electronic data interchange) code was used as it is. Extraction, conversion and loading were completed. R language-based conversion and loading software for the process was developed, and clinical data warehouse construction was completed through data verification. Practical Implications: In this study, a clinical data warehouse for Dankook university hospitals based on a common data model supporting drug surveillance research was established and verified. The results of this study provide guidelines for institutions that want to build a clinical data warehouse in the future by deriving key points necessary for building a clinical data warehouse.

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생물학적 자극 통제 수단으로서 활용하기 위한 돼지 페로몬성 냄새 물질의 탐색: I. 5$\alpha$-androst-16-en-3-one 유사체들의 리간드에 기초한 분자 유사성과 물리화학 파라미터 (The Search of fig Pheromonal Odorants for Biostimulation Control System Technologies: I. Ligand Based Molecular Shape Similarity of 5$\alpha$-androst-16-en-3-one Analogous and Their Physicochemical Parameters)

  • 성낙도;김철호;진동일;박창식
    • Reproductive and Developmental Biology
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    • 제28권1호
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    • pp.45-52
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    • 2004
  • To search a new porcine pheromonal odorants, this research for biostimulation and role of pheromone was augmented by means of "control system technologies" to offer a potentially useful and practical way to improve reproductive efficiency in livestock species. Therefore the 13 physicochemical parameters such as similarity indice (S), hydrophobicity (logP) and van der Waals molecule volume (MV) etc. of 54 steroid analogues, which are analogous of substrate molecules, 5$\alpha$-androst-16-en-3-one (P1) and 5$\alpha$-androst-16-en-3-ol (P2) of lipocalin as receptor of pig pheromones were calculated and discussed. The physicochemical properties of these steroid analogues were mainly followed by steric dissimilar of A and D ring in steroid nucleus. And we found that from correlation with S values and MV constants of molecules, the more MV constants are small, the more S values tend to approach 1. Based on this results, the S-values of 4-androsten-3,17-dione (P1-1) and 5 $\alpha$ -androstan-3-one (P2-1) were 1.0, respectively. The two compounds of them were chosen because they showed the same value each other at a side of hydrophobicity, molar refractivity and molecular volume. It is expected that the new two compounds will be able to substitute for P1 and P2, porcine pheromonal odorants.

토양생태계 위해성평가기법 비교연구: 토양생태준거치 산정을 중심으로 (Comparative study of Ecological Risk Assessment : Deriving Soil Ecological Criteria)

  • 이우미;김신웅;정승우;안윤주
    • 한국지하수토양환경학회지:지하수토양환경
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    • 제17권5호
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    • pp.1-9
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    • 2012
  • The purpose of ecological risk assessment in soil ecosystem is to protect ecological receptors and to provide a scheme of efficient management for soil contaminants. Developed countries have already prepared the methodologies of ecological risk assessment by considering their soil properties, land use, and ecological receptors. In this study, we compared the soil ecological risk assessment processes in the similarity and differences in methodology. Four countries, except for USA, adjusted the toxicological data for ecological risk assessment, based on their representative soil properties because the soil properties affect toxic effects to ecological receptors. The soil ecological risk assessment methodology of Netherlands and UK was based on 'Technical guidance document on risk assessment (TGD)' of European Chemical Bureau (ECB). Australia, USA, and Canada developed their autonomous methodology. In the Netherlands, UK, Australia, and Canada, they employed the species sensitivity distribution (SSD) approach if sufficient toxicity data are available. The USA determined the ecological soil screening level by obtaining the geometric mean of toxicological data for three species. Furthermore, all countries consider secondary poisoning in their soil ecological risk assessment. The latest risk assessment methodology of soil ecosystem that this study investigated can be used to explore what Korea needs to develop the Korean ecological risk assessment methodology of soil ecosystem in the future.

피부 섬유아세포에서 다이드제인의 파이토에스트로겐 효과 (The Phytoestrogenic Effect of Daidzein in Human Dermal Fibroblasts)

  • 김미선;홍찬영;이상화
    • 대한화장품학회지
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    • 제40권3호
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    • pp.279-287
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    • 2014
  • 폐경 이후 여성에서 발생되는 에스트로겐의 감소는 피부노화와 밀접한 관련이 있으며, 피부의 정상적 상태와 기능을 저하시키게 된다. 지난 10여 년간 보고된 많은 연구결과를 살펴보면, 에스트로겐은 폐경 이후 여성의 피부에서 콜라겐 감소를 막아주고, 탄력을 회복시키며, 건조한 피부를 개선시키는 등의 피부 안티에이징 효능을 가지는 것을 알 수 있다. 에스트로겐과 유사한 구조로 인해 파이토에스트로겐이라 알려진 이소플라본은 자외선에 의해 유도된 피부 손상을 보호하는 기작이 널리 알려져 왔으나 피부세포에서 에스트로겐과 유사한 안티에이징 효능을 가지는지에 대해서는 많은 연구가 진행되지 않았다. 이에 본 연구에서는 콩류 등에 많이 함유된 이소플라본인 다이드제인이 에스트로겐과 유사한 활성 및 효능을 가지는지 밝히고자 하였다. 먼저 에스트로겐 수용체와의 결합을 통한 transcriptional activity에 미치는 효과를 luciferase assay를 통해 살펴본 결과, 다이드제인은 대조군에 비해 농도 의존적으로 estrogen receptor-dependent transcriptional activity를 유의하게 증가시켰다. 다음으로 사람의 피부 섬유아세포를 이용하여 다이드제인이 세포외 기질단백질 성분들의 발현에 미치는 효과를 조사한 결과, 다이드제인은 콜라겐 타입 I, 콜라겐 타입 IV, 엘라스틴 및 피브릴린-1의 발현을 유의하게 증가시키는 것을 확인할 수 있었다. 모든 실험조건에서 에스트로겐 단독 효능과의 비교 분석을 통해 다이드제인은 에스트로겐과 유사한 효능을 가진다는 것을 확인할 수 있었다. 본 연구 결과를 통해 다이드제인은 기존에 알려진 이소플라본의 광보호 효능과 더불어 파이토에스트로겐 효능을 가짐으로써 갱년기 여성의 피부 안티에이징을 위해 활용할 수 있을 것이라 제안한다.

공기괴 역궤적 모델의 통계 분석을 통한 이산화탄소 배출 지역 추정 (Statistical Back Trajectory Analysis for Estimation of CO2 Emission Source Regions)

  • 이선란;박선영;박미경;조춘옥;김재연;김지윤;김경렬
    • 대기
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    • 제24권2호
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    • pp.245-251
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    • 2014
  • Statistical trajectory analysis has been widely used to identify potential source regions for chemically and radiatively important chemical species in the atmosphere. The most widely used method is a statistical source-receptor model developed by Stohl (1996), of which the underlying principle is that elevated concentrations at an observation site are proportionally related to both the average concentrations on a specific grid cell where the observed air mass has been passing over and the residence time staying over that grid cell. Thus, the method can compute a residence-time-weighted mean concentration for each grid cell by superimposing the back trajectory domain on the grid matrix. The concentration on a grid cell could be used as a proxy for potential source strength of corresponding species. This technical note describes the statistical trajectory approach and introduces its application to estimate potential source regions of $CO_2$ enhancements observed at Korean Global Atmosphere Watch Observatory in Anmyeon-do. Back trajectories are calculated using HYSPLIT 4 model based on wind fields provided by NCEP GDAS. The identified $CO_2$ potential source regions responsible for the pollution events observed at Anmyeon-do in 2010 were mainly Beijing area and the Northern China where Haerbin, Shenyang and Changchun mega cities are located. This is consistent with bottom-up emission information. In spite of inherent uncertainties of this method in estimating sharp spatial gradients within the vicinity of the emission hot spots, this study suggests that the statistical trajectory analysis can be a useful tool for identifying anthropogenic potential source regions for major GHGs.

A comparative review of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia: exploring the factors behind epinephrine's prevalence in the US

  • Navkiran Deol;Gerardo Alvarez;Omar Elrabi;Gavin Chen;Nalton Ferraro
    • Journal of Dental Anesthesia and Pain Medicine
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    • 제23권6호
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    • pp.293-302
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    • 2023
  • This review paper delves into the comparative study of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia, exploring their histories, pharmacological properties, and clinical applications. The study involved a comprehensive literature search, focusing on articles that directly compared the two agents in terms of efficacy, safety, and prevalence in dental anesthesia. Epinephrine, with its broad receptor profile, has been a predominant choice, slightly outperforming in the context of prolonging dental anesthesia and providing superior hemostasis, which is crucial for various dental procedures. However, the stimulation of beta-adrenergic receptors caused by epinephrine poses risks, especially to patients with cardiovascular conditions. Phenylephrine, a selective alpha-1 adrenergic agonist, emerges as a safer alternative for such patients, avoiding the cardiovascular risks associated with epinephrine. Moreover, its vasoconstrictive effect may not be as deleterious as that of epinephrine, due to its selective action. This review reveals that despite the potential benefits of phenylephrine, epinephrine continues to dominate in clinical settings, due to its historical familiarity, availability, and cost-effectiveness. The lack of commercially available pre-made phenylephrine dental carpules in most countries, except Brazil, and a knowledge gap within dental academia regarding phenylephrine, contribute to its limited use. This review concludes that while both agents are effective, the choice between them should be based on individual patient conditions, availability, and the practitioner's knowledge and familiarity with the agents. The underuse of other vasoconstrictors like levonordefrin and the unavailability of phenylephrine in pre-mixed dental cartridges in many countries highlights the need for further exploration and research in this field. Furthermore, we also delve into the role of levonordefrin and examine the rationale behind the exclusion of phenylephrine from commercially available pre-mixed local anesthetic carpules, suggesting a need for a responsive approach from pharmaceutical manufacturers to the distinct needs of the dental community.

Ligand Based Pharmacophore Identification and Molecular Docking Studies for Grb2 Inhibitors

  • Arulalapperumal, Venkatesh;Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Lee, Yun-O;Meganathan, Chandrasekaran;Hwang, Swan;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • 제33권5호
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    • pp.1707-1714
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    • 2012
  • Grb2 is an adapter protein involved in the signal transduction and cell communication. The Grb2 is responsible for initiation of kinase signaling by Ras activation which leads to the modification in transcription. Ligand based pharmacophore approach was applied to built the suitable pharmacophore model for Grb2. The best pharmacophore model was selected based on the statistical values and then validated by Fischer's randomization method and test set. Hypo1 was selected as a best pharmacophore model based on its statistical values like high cost difference (182.22), lowest RMSD (1.273), and total cost (80.68). It contains four chemical features, one hydrogen bond acceptor (HBA), two hydrophobic (HY), and one ring aromatic (RA). Fischer's randomization results also shows that Hypo1 have a 95% significant level. The correlation coefficient of test set was 0.97 which was close to the training set value (0.94). Thus Hypo1 was used for virtual screening to find the potent inhibitors from various chemical databases. The screened compounds were filtered by Lipinski's rule of five, ADMET and subjected to molecular docking studies. Totally, 11 compounds were selected as a best potent leads from docking studies based on the consensus scoring function and critical interactions with the amino acids in Grb2 active site.

Differentially Expressed Proteins in ER+ MCF7 and ER- MDA-MB-231 Human Breast Cancer Cells by RhoGDI-α Silencing and Overexpression

  • Hooshmand, Somayeh;Ghaderi, Abbas;Yusoff, Khatijah;Thilakavathy, Karuppiah;Rosli, Rozita;Mojtahedi, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3311-3317
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    • 2014
  • Background: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDI${\alpha}$) activity on migration and invasion of estrogen receptor positive ($ER^+$) and negative ($ER^-$) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDI${\alpha}$ and other proteins interacting directly or indirectly with RhoGDI${\alpha}$ in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. Materials and Methods: $ER^+$ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDI${\alpha}$ using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDI${\alpha}$. Results: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDI${\alpha}$ in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDI${\alpha}$ in MCF7, while only one protein was identified in the upregulation of RhoGDI${\alpha}$ in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-${\alpha}$ activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Conclusions: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDI${\alpha}$ with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.