• 제목/요약/키워드: Target profiling

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Tyrosine Kinase Inhibitors in Ph+ Chronic Myeloid Leukemia Therapy: a Review

  • Shah, Krupa;Parikh, Sonia;Rawal, Rakesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3025-3033
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    • 2016
  • Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

MALDI-TOF MS System for the Identification of Microorganisms in Milk and Dairy Products (우유 및 유제품 중 미생물 동정을 위한 MALDI-TOFMS활용)

  • Kim, Hyoun Wook;Ham, Jun-Sang;Seol, Kuk-Hwan;Han, Sangha;Park, Beam Young;Oh, Mi-Hwa
    • Journal of Dairy Science and Biotechnology
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    • v.30 no.2
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    • pp.131-137
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    • 2012
  • Rapid and reliable identification of microorganisms is a key for tracing the relationship between the target bacteria and related infectious diseases. Various identification methods such as classical phenotypic analysis, numerical taxonomic analysis, and DNA sequencing have been widely used to classify microorganisms in milk and dairy products. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) identifies targeted bacteria in milk and milk products. Several studies have demonstrated that MALDI-TOF MS identification is an efficient and inexpensive method for the rapid and routine identification of isolated bacteria. MALDI-TOF MS could provide accurate identification of bacteria in milk and milk products at the serotype or strain level and enable antibiotic resistance profiling within minutes.

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CS Road Map unifying service quality managment, customer satisfaction and value creation (서비스 품질 관리를 통한 고객 만족과 가치 창출을 위한 Road Map)

  • 우지영;윤의탁;박상찬
    • Proceedings of the Korean Society for Quality Management Conference
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    • 2004.04a
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    • pp.371-375
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    • 2004
  • As the importance of customers has been emphasized, most companies began to operate various CRM strategies to understand and manage customers' needs. The investments that businesses are making are categorized into four areas. The first area of investments is in contact centers and channels to manage the voice of customers. The second area is in loyalty management, target marketing using segmentation, profiling, profitability analysis and targeting. The third one is involved in the measurement of customer satisfaction. The last one is planning to deliver products and services to appropriate customers. Despite the various efforts, it is lowering the efficiency of these investments and interrupting their value creation that these are being operated independently in different departments. All CRM activities of an enterprise should be processed interactively and consistently for a common goal; value creation, to overcome these shortcomings. In this research, we propose CS Road Map that systematizes the four kinds of CRM activities; VOC management, survey activities, loyalty management and planning. Under this road map, these four activities will achieve the improvement of service qualities, customer satisfaction and further value creation. This paper demonstrates the road map that is built for a service industry emphasizing the objectives and strategies of the four categories.

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Calibration of Structured Light Vision System using Multiple Vertical Planes

  • Ha, Jong Eun
    • Journal of Electrical Engineering and Technology
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    • v.13 no.1
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    • pp.438-444
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    • 2018
  • Structured light vision system has been widely used in 3D surface profiling. Usually, it is composed of a camera and a laser which projects a line on the target. Calibration is necessary to acquire 3D information using structured light stripe vision system. Conventional calibration algorithms have found the pose of the camera and the equation of the stripe plane of the laser under the same coordinate system of the camera. Therefore, the 3D reconstruction is only possible under the camera frame. In most cases, this is sufficient to fulfill given tasks. However, they require multiple images which are acquired under different poses for calibration. In this paper, we propose a calibration algorithm that could work by using just one shot. Also, proposed algorithm could give 3D reconstruction under both the camera and laser frame. This would be done by using newly designed calibration structure which has multiple vertical planes on the ground plane. The ability to have 3D reconstruction under both the camera and laser frame would give more flexibility for its applications. Also, proposed algorithm gives an improvement in the accuracy of 3D reconstruction.

A Universal Analysis Pipeline for Hybrid Capture-Based Targeted Sequencing Data with Unique Molecular Indexes

  • Kim, Min-Jung;Kim, Si-Cho;Kim, Young-Joon
    • Genomics & Informatics
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    • v.16 no.4
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    • pp.29.1-29.5
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    • 2018
  • Hybrid capture-based targeted sequencing is being used increasingly for genomic variant profiling in tumor patients. Unique molecular index (UMI) technology has recently been developed and helps to increase the accuracy of variant calling by minimizing polymerase chain reaction biases and sequencing errors. However, UMI-adopted targeted sequencing data analysis is slightly different from the methods for other types of omics data, and its pipeline for variant calling is still being optimized in various study groups for their own purposes. Due to this provincial usage of tools, our group built an analysis pipeline for global application to many studies of targeted sequencing generated with different methods. First, we generated hybrid capture-based data using genomic DNA extracted from tumor tissues of colorectal cancer patients. Sequencing libraries were prepared and pooled together, and an 8-plexed capture library was processed to the enrichment step before 150-bp paired-end sequencing with Illumina HiSeq series. For the analysis, we evaluated several published tools. We focused mainly on the compatibility of the input and output of each tool. Finally, our laboratory built an analysis pipeline specialized for UMI-adopted data. Through this pipeline, we were able to estimate even on-target rates and filtered consensus reads for more accurate variant calling. These results suggest the potential of our analysis pipeline in the precise examination of the quality and efficiency of conducted experiments.

GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways

  • Gang Wang;Baisha Ouyang;Fang Jing;Xiaoyan Dai
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.21-29
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    • 2023
  • The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

Mutational Analysis of Key EGFR Pathway Genes in Chinese Breast Cancer Patients

  • Tong, Lin;Yang, Xue-Xi;Liu, Min-Feng;Yao, Guang-Yu;Dong, Jian-Yu;Ye, Chang-Sheng;Li, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5599-5603
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    • 2012
  • Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

Tissue Microarrays in Biomedical Research

  • Chung, Joon-Yong;Kim, Nari;Joo, Hyun;Youm, Jae-Boum;Park, Won-Sun;Lee, Sang-Kyoung;Warda, Mohamad;Han, Jin
    • Bioinformatics and Biosystems
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    • v.1 no.1
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    • pp.28-37
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    • 2006
  • Recent studies in molecular biology and proteomics have identified a significant number of novel diagnostic, prognostic, and therapeutic disease markers. However, validation of these markers in clinical specimens with traditional histopathological techniques involves low throughput and is time consuming and labor intensive. Tissue microarrays (TMAs) offer a means of combining tens to hundreds of specimens of tissue onto a single slide for simultaneous analysis. This capability is particularly pertinent in the field of cancer for target verification of data obtained from cDNA micro arrays and protein expression profiling of tissues, as well as in epidemiology-based investigations using histochemical/immunohistochemical staining or in situ hybridization. In combination with automated image analysis, TMA technology can be used in the global cellular network analysis of tissues. In particular, this potential has generated much excitement in cardiovascular disease research. The following review discusses recent advances in the construction and application of TMAs and the opportunity for developing novel, highly sensitive diagnostic tools for the early detection of cardiovascular disease.

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Characterization of the Effects of Silver Nanoparticles on Liver Cell Using HR-MAS NMR Spectroscopy

  • Kim, Si-Won;Kim, So-Sun;Lee, Sang-Mi;Kwon, Bo-Bae;Choi, Jin-Hee;Hyun, Jin-Won;Kim, Suhk-Mann
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.2021-2026
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    • 2011
  • AgNPs (silver nanoparticles) has been widely used for the commercial products, which have antimicrobial agent, medical devices, food industry and cosmetics. Despite, AgNPs have been reported as toxic to the mammalian cell, lung, liver, brain and other organs and many researchers have investigated the toxicity of AgNPs. In this study, we investigated toxicity of the AgNPs to the liver cell using metabolomics based on HRMAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Resonance) technics, which could apply to the intact tissues or cells, to avoid the sample destruction. Target profiling and multivariative statistical analysis were performed to analyze the 1D $^1H$ spectrum. The results show that the concentrations of many metabolites were affected by the AgNPs in the liver cell. The concentrations of glutathione (GSH), lactate, taurine, and glycine were decreased and most of amino acids, choline analogues, and pyruvate were increased by the AgNPs. Moreover, the levels of the metabolites were recovered upto similar level of metabolites in the normal cell by the pre-treatment of NAC, external antioxidant. The results suggest that the depletion of the GSH by the AgNPs might induce the conversion of lactate and taurine to the pyruvate.

Circulating microRNA expression profiling in young obese Korean women

  • Choi, Won Hee;Ahn, Jiyun;Um, Min Young;Jung, Chang Hwa;Jung, Sung Eun;Ha, Tae Youl
    • Nutrition Research and Practice
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    • v.14 no.4
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    • pp.412-422
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    • 2020
  • BACKGROUND/OBJECTIVES: This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20-30 years old) in Korea. SUBJECTS/METHODS: We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/㎡) and 15 obese (BMI > 25 kg/㎡) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. RESULTS: The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324-3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = -0.5484, P = 0.0056; miR-378, r = -0.5538, P = 0.0050) and visceral fat content (miR-484, r = -0.6141, P = 0.0014; miR-378, r = -0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. CONCLUSION: Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.