• Title/Summary/Keyword: Target Identification

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Discovery of Urinary Biomarkers in Patients with Breast Cancer Based on Metabolomics

  • Lee, Jeongae;Woo, Han Min;Kong, Gu;Nam, Seok Jin;Chung, Bong Chul
    • Mass Spectrometry Letters
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    • v.4 no.4
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    • pp.59-66
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    • 2013
  • A metabolomics study was conducted to identify urinary biomarkers for breast cancer, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), analyzed by principal components analysis (PCA) as well as a partial least squares-discriminant analysis (PLS-DA) for a metabolic pattern analysis. To find potential biomarkers, urine samples were collected from before- and after-mastectomy of breast cancer patients and healthy controls. Androgens, corticoids, estrogens, nucleosides, and polyols were quantitatively measured and urinary metabolic profiles were constructed through PCA and PLS-DA. The possible biomarkers were discriminated from quantified targeted metabolites with a metabolic pattern analysis and subsequent screening. We identified two biomarkers for breast cancer in urine, ${\beta}$-cortol and 5-methyl-2-deoxycytidine, which were categorized at significant levels in a student t-test (p-value < 0.05). The concentrations of these metabolites in breast cancer patients significantly increased relative to those of controls and patients after mastectomy. Biomarkers identified in this study were highly related to metabolites causing oxidative DNA damage in the endogenous metabolism. These biomarkers are not only useful for diagnostics and patient stratification but can be mapped on a biochemical chart to identify the corresponding enzyme for target identification via metabolomics.

Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models

  • Vinayak, Rashmi;Puttananjaiah, Shilpa;Chatterji, Anil;Salimath, Bharati
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.377-385
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    • 2014
  • BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

Identification and Functional Analysis of Differentially Expressed Genes Related to Metastatic Osteosarcoma

  • Niu, Feng;Zhao, Song;Xu, Chang-Yan;Chen, Lin;Ye, Long;Bi, Gui-Bin;Tian, Gang;Gong, Ping;Nie, Tian-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10797-10801
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    • 2015
  • Background: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. Materials and Methods: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). Results: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. Conclusions: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS.

Identification of Histone Deacetylase 1 Protein Complexes in Liver Cancer Cells

  • Farooq, Muhammad;Hozzein, Wael N.;Elsayed, Elsayed A.;Taha, Nael A.;Wadaan, Mohammad A.M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.915-921
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    • 2013
  • Background: Hepatocellular carcinoma is one of the leading causes of mortalities worldwide. The search for new therapeutic targets is of utmost importance for improved treatment. Altered expression of HDAC1 in hepatocellular carcinoma (HCC) and its requirement for liver formation in zebrafish, suggest that it may regulate key events in liver carcinogenesis and organogenesis. However, molecular mechanisms of HDAC1 action in liver carcinogenesis are largely unknown. The present study was conducted to identify HDAC1 interacting proteins in HepG2 cells using modified SH-double-affinity purification coupled with liquid mass spectrophotemetery. Materials and Methods: HepG2 cells were transfected with a construct containing HDAC1 with a C-terminal strepIII-HA tag as bait. Bait proteins were confirmed to be expressed in HepG2 cells by western blotting and purified by double affinity columns and protein complexes for analysis on a Thermo LTQ Orbitrap XL using a C18 nano flow ESI liquid chromatography system. Results: There were 27 proteins which showed novel interactions with HDAC1 identified only in this study, while 14 were among the established interactors. Various subunits of T complex proteins (TCP1) and prefoldin proteins (PFDN) were identified as interacting partners that showed high affinity with HDAC1 in HepG2 cells. Conclusions: The double affinity purification method adopted in this study was very successful in terms of specificity and reproducibility. The novel HDAC1 complex identified in this study could be better therapeutic target for treatment of hepatocellular carcinoma.

Development of Korean Consonant Perception Test (자음지각검사 (KCPT)의 개발)

  • Kim, Jin-Sook;Shin, Eun-Yeong;Shin, Hyun-Wook;Lee, Ki-Do
    • The Journal of the Acoustical Society of Korea
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    • v.30 no.5
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    • pp.295-302
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    • 2011
  • The purpose of this study was to develop Korean Consonant Perception Test (KCPT), that is a phonemic level including elementary data to evaluate speech and consonant perception ability of the normal and the hearing impaired qualitatively and quantitatively. KCPT was completed with meaningful monosyllabic words out of possible all Korean monosyllabic words, considering articulation characteristics, the degree of difficulty, and the frequency of the phonemic appearance, after assembling a tentative initial and final consonants testing items using four multiple-choice method which were applied to the seven final consonant regulation and controlled with the familiarity of the target words. Conclusively, the final three hundred items were developed including two- and one-hundred items for initial and final testing items, respectively, with the evaluation of the 20 normal hearing adults. Through this process, the final KCPT was composed upon the colloquial frequency following identification of no speakers' variances statistically and elimination of the highly difficult items. The 30 hearing impaired were tested with KCPT and found that the half lists, A and B, were not different statistically and the initial and final testing items were appropriate for evaluating initial and final consonants, respectively.

Identification, Fermentation, and Bioactivity Against Xanthomonas oryzae of Antimicrobial Metabolites Isolated from Phomopsis longicolla S1B4

  • Lim, Chae-Sung;Kim, Ji-Young;Choi, Jung-Nam;Ponnusamy, Kannan;Jeon, Yul-Taek;Kim, Soo-Un;Kim, Jeong-Gu;Lee, Choong-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.20 no.3
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    • pp.494-500
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    • 2010
  • Bacterial blight, an important and potentially destructive bacterial disease in rice, is caused by Xanthomonas oryzae. Recently, this organism has developed resistance to available antibiotics, prompting scientists to find a suitable alternative. This study focused on secondary metabolites of Phomopsis longicolla to target X. oryzae. Five bioactive compounds were isolated by activity-guided fractionation from ethyl acetate extracts of mycelia and were identified by LC/MS and NMR spectroscopy as dicerandrol A, dicerandrol B, dicerandrol C, deacetylphomoxanthone B, and fusaristatin A. This is the first time fusaristatin A has been isolated from Phomopsis sp. Deacetylphomoxanthone B showed a higher antibacterial effect against X. oryzae KACC 10331 than the positive control (2,4-diacetyphloroglucinol). Dicerandrol A also showed high antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and yeast (Candida albicans). In addition, high production yields of these compounds were obtained at the stationary and death phases.

Source Identification and Quantification of Coarse and Fine Particles by TTFA and PMF

  • Hwang, In-Jo;Bong, Choon-Keun;Lee, Tae-Jung;Kim, Dong-Sool
    • Journal of Korean Society for Atmospheric Environment
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    • v.18 no.E4
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    • pp.203-213
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    • 2002
  • Receptor modeling is one of statistical methods to achieve reasonable air pollution strategies. In order to maintain and manage ambient air quality, it is necessary to identify sources and to apportion its sources for ambient particulate matters. The main purpose of the study was to survey seasonal trends of inorganic elements in the coarse and fine particles. Second, this study has attempted emission sources qualitatively by a receptor method, the PMF mo-del. After that. both PMF (positive matrix factorization) model and TTFA (target transformation factor analysis) model were applied to compare and to estimate mass contribution of coarse and fine particle sources at the receptor. A total of 138 sets of samples was collected from 1989 to 1996 by a low volume cascade impactor with 9 size fraction stages at Kyung Hee University in Korea. Sixteen chemical species (Si, Ca, Fe, K, Pb, Na, Zn, Mg, Ba, Ni, V, Mn, Cr, Br, Cu. Co) were characterized by XRF. The study result showed that the weighted arithmetic mean of coarse and fine particles were 51.3 and 54.4 $\mu\textrm{g}$/㎥, respectively. Contribution of both particle fractions were esti-mated using TTFA and PMF models. The number of estimated sources was seven according to TTFA model and 8 according to PMF model. Comparison of TTFA and PMF revealed that both methodologies exhibited similar trends in their contribution pattern. However, large differences between contributions were observed in some sour-ces. The results of this study may help to suggest control strategies in local countries where known source profiles do not exist.

Wearable Robot System Enabling Gaze Tracking and 3D Position Acquisition for Assisting a Disabled Person with Disabled Limbs (시선위치 추적기법 및 3차원 위치정보 획득이 가능한 사지장애인 보조용 웨어러블 로봇 시스템)

  • Seo, Hyoung Kyu;Kim, Jun Cheol;Jung, Jin Hyung;Kim, Dong Hwan
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.37 no.10
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    • pp.1219-1227
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    • 2013
  • A new type of wearable robot is developed for a disabled person with disabled limbs, that is, a person who cannot intentionally move his/her legs and arms. This robot can enable the disabled person to grip an object using eye movements. A gaze tracking algorithm is employed to detect pupil movements by which the person observes the object to be gripped. By using this gaze tracking 2D information, the object is identified and the distance to the object is measured using a Kinect device installed on the robot shoulder. By using several coordinate transformations and a matching scheme, the final 3D information about the object from the base frame can be clearly identified, and the final position data is transmitted to the DSP-controlled robot controller, which enables the target object to be gripped successfully.

Limits of Direct PCR Amplification from Seaweeds Using Arbitrary and ITS Primers (해조류로부터 Arbitrary 및 ITS Primer들을 사용한 직접 PCR 유전자 증폭반응의 한계)

  • 김용국;진형주;박선미;진덕희;홍용기
    • Journal of Life Science
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    • v.9 no.1
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    • pp.15-21
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    • 1999
  • The random amplified ploymorphic DNAs (RAPD) assay is a simple and useful tool in identification of appropriate genetic markers, that requires no knowledge of target DNA sequence. RAPD products were generated directly from seaweed tissues, without prior nucleic acid extraction, of Porphyra yezoensis, Ulva pertusa and Undaria pinnatifida. The nuclear rDNA internal transcribed spacer (ITS) fragment however was not amplified directly from the seaweed tissues. Using DNA extracted by the LiCl method, both the ITS and RAPD's have been amplified by the polymerase chain reaction. RAPD of P yezoensis, thallus (n) and conchocelis (2n) produced lots of different polymorphic bands (36-50$\%$) depending on the arbitrary primers used. Difference was also observed between direct tissues amplification and DNA extracts amplification (53-57$\%$). Thus it is important to use the same ploidy of tissue for DNA extraction and as a RAPD template.

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Identification of Salmonella Enteritidis and S. Typhimurium by multiplex polymerase chain reaction (Multiplex PCR 기법을 이용한 Salmonella Enteritidis와 S. Typhimurium의 특이적 검출에 관한 연구)

  • Lee, Woo-Won;Lee, Seung-Mi;Lee, Gang-Rok;Lee, Dong-Soo;Park, Ho-Kuk
    • Korean Journal of Veterinary Service
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    • v.32 no.2
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    • pp.147-153
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    • 2009
  • Salmonella species are the most important etiologic agents of food-borne acute gastroenteritis. The most common serotypes isolated from humans are Salmonella enterica serotype Typhimurium (S. Typhimurium) and S. Enteritidis. Traditional detection methods for Salmonella are based on cultures using selective media and characterization of suspicious colonies by biochemical and serological tests. These methods are generally time-consuming and not so highly sensitive. Recently, the polymerase chain reaction (PCR) has been used as a highly sensitive, specific, and rapid test for the presence of pathogenic bacteria. In this study, a multiplex PCR (m-PCR) was used to detect S. Typhimurium and S. Enteritidis. We selected m-PCR target genes, which were the spv (virulence plasmid specific for S. Enteritidis) and sefA (S. Enteritidis fimbrial antigen) genes, fliC (H1-i antigen specific for S. Typhimurium) and a randomly cloned sequence specific for the genus Salmonella. With m-PCR, random sequence was detected from all strains of Salmonella spp, spv and sefA were detected from all strains of S. Enteritidis (100%), and fliC was detected from all strains of S. Typhimurium (100%). This assay indicate that the specificity of the m-PCR make them potentially valuable tools for detection of S. Typhimurium and S. Enteritidis.