• Title/Summary/Keyword: molecular profile

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Descriptor-Based Profile Analysis of Kinase Inhibitors to Predict Inhibitory Activity and to Grasp Kinase Selectivity

  • Park, Hyejin;Kim, Kyeung Kyu;Kim, ChangHoon;Shin, Jae-Min;No, Kyoung Tai
    • Bulletin of the Korean Chemical Society
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    • v.34 no.9
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    • pp.2680-2684
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    • 2013
  • Protein kinases (PKs) are an important source of drug targets, especially in oncology. With 500 or more kinases in the human genome and only few kinase inhibitors approved, kinase inhibitor discovery is becoming more and more valuable. Because the discovery of kinase inhibitors with an increased selectivity is an important therapeutic concept, many researchers have been trying to address this issue with various methodologies. Although many attempts to predict the activity and selectivity of kinase inhibitors have been made, the issue of selectivity has not yet been resolved. Here, we studied kinase selectivity by generating predictive models and analyzing their descriptors by using kinase-profiling data. The 5-fold cross-validation accuracies for the 51 models were between 72.4% and 93.7% and the ROC values for all the 51 models were over 0.7. The phylogenetic tree based on the descriptor distance is quite different from that generated on the basis of sequence alignment.

Construction and Validation of Human cDNA Microarray for Estimation of Endocrine Disrupting Chemicals (KISTCHIP-400 ver. 1.0)

  • Ryu, Jae-Chun;Kim, Youn-Jung
    • Molecular & Cellular Toxicology
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    • v.1 no.1
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    • pp.52-61
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    • 2005
  • Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an awareness of endocrine disrupting chemicals (EDCs) and their potential screening methods to identify endocrine activity have been increased. Here we developed an in-house cDNA microarray, named KISTCHIP-400 ver. 1.0, with 416 clones, based on public database and research papers. These clones contained estrogen, androgen, thyroid hormone & receptors, sex hormone signal transduction & regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. Also, to validate the KISTCHIP-400 ver. 1.0, we investigated gene expression profiles with reference hormones, $10^{8}\;M\;17{\beta}-estradiol,\;10^{-7}\;M\;testosterone\;and\;10^{-7}\;M$ progesterone in MCF-7 cell line. As the results, gene expression profiles of three reference hormones were distinguished from each other with significant and identified 33 $17{\beta}-estradiol$ responsive genes. This study is in first step of validation for KISTCHIP-400 ver. 1.0, as following step transcriptional profile analysis on not only low concentrations of EDCs but suspected EDCs using KISTCHIP-400 ver. 1.0 is processing. Our results indicate that the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

Gene Expression Profile in Iprobenfos Exposed Medaka Fish by Microarray Analysis

  • Woo, Seon-Ock;Son, Sung-Hee;Ryu, Jae-Chun;Yum, Seung-Shic
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.132-137
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    • 2008
  • Differential gene expression profiling was carried out in the hepatic tissue of medaka fish, Oryzias latipes, after exposure to an organophosphorus pesticide (OPP), Iprobenfos (IBP), a widely used pesticide in agri- and fish-culture, using a medaka cDNA micro array. Twenty six kinds of differentially expressed candidate genes, with 15 and 11 induced and repressed in their gene expressions, respectively, were associated with cytoskeleton (3.8%), development (7.7%), immune (7.7%), metabolism (30.8%), nucleic acid/protein binding (42.3%) and reproduction (7.7%). Of these genes, changes at the transcription level of five were re-evaluated by real-time quantitative PCR (qRT-PCR). Considering the known function of authentic genes, the effects of IBP on the biological activity and pathological aspects in medaka fish were discussed. The identified genes could be used as molecular biomarkers for biological responses to OPPs contamination in an aquatic environment.

Manifestation of metabolic Aberration in Rat urine Following Hypothalamic Lesions

  • Anbar, Michel;Kim, Kyoung-Rae
    • Archives of Pharmacal Research
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    • v.7 no.2
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    • pp.101-107
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    • 1984
  • The concentrations of metabolites of low molecular weights (90 to 310 amu) present in rat urine were determined by field ionization mass spectrometry. Three groups of rats were examined; intact controls, sham-operated rats and rats with selective lesions in their hypothalamus. The latter lesions are shown to induce characteristic aberrations in the metabolic profile, demonstrable five weeks after treatment, which are distinct from those induced by a sham operation.

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Free molecule transmission probability of a conical tube with wall sorption

  • 인상렬
    • Journal of Korean Vacuum Science & Technology
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    • v.2 no.1
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    • pp.1-8
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    • 1998
  • The uniform distributed pumping model is used to derive analytic expressions of the pressure profile for the molecular flow regime in linearly tapered or flared(conical or pyramidal) tubes with wall sorption. The concept of transmission conductance for sticky tubes of arbitrary shape is newly introduced to calculate the transmission probability using the pressure profile. The transmission probability obtained analytically for a conical sticky tube is compared with that from the Monte Carlo simulation.

The Interaction of Phenylthiourea Derivatives as Catechol Oxidase Inhibitors by Molecular Mechanics Simulation (페닐티오우레아 유도체와 카테콜 산화효소와의 상호작용에 대한 분자역학적 모의실험)

  • Park, Kyung Lae
    • YAKHAK HOEJI
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    • v.60 no.2
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    • pp.78-84
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    • 2016
  • N-Phenylthiourea derivatives and catechol oxidase receptor complex was studied using molecular mechanics method. The starting structure was adopted from the protein databank and the calculation of energy minimization and molecular dynamics was performed with AMBER package. The molecular dynamics showed that the simulation time span of 20 ns was long enough to observe the interaction profile and stationary ligand-receptor configuration in the complex. The conformation of the ligand was related to the interaction to the receptor and the efficacy was also interpreted in this context.

Simulation of Molecular Flows Inside a Guide Block in the OLED Deposition Process (OLED 박막 증착공정에서 유도로 내부의 분자유동 해석)

  • Sung, Jae-Yong;Lee, Eung-Ki
    • Transactions of the Korean Society of Machine Tool Engineers
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    • v.17 no.2
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    • pp.45-50
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    • 2008
  • Molecular flows inside a guide block in the OLED(organic luminescent emitting device) deposition process have been simulated using DSMC(direct simulation Monte Carlo) method. Because the organic materials are evaporated under vacuum, molecules flow at a high Knudsen number of the free molecular regime, where the continuum mechanics is not valid. A guide block is designed as a part of the linear cell source to transport the evaporated materials to a deposition chamber, When solving the flows, the inlet boundary condition is proved to affect significantly the whole flow pattern. Thus, it is proposed that the pressure should be specified at the inlet. From the analysis of the density distributions at the nozzle exit of the guide block, it is shown that the longer nozzle can emit molecules more straightly. Finally, a nondimensionalized mass flow profile is obtained by numerical experiments, where various nozzle widths and inlet pressures are tested.

Molecular Classification of Hepatocellular Carcinoma and Its Impact on Prognostic Prediction and Personized Therapy

  • Dhruba Kadel;Lun-Xiu Qin
    • Journal of Digestive Cancer Research
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    • v.5 no.1
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    • pp.5-15
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    • 2017
  • Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related death in the world. The aggressive but not always predictable pattern of HCC causes the limited treatment option and poorer outcome. Many researches had already proven the heterogeneity of HCC is one of the major challenges for treatment option and prognosis prediction. Molecular subtyping of HCC and selection of patient based on molecular profile can provide the optimization in the treatment and prognosis prediction. In this review, we have tried to summarize the molecular classification of HCC proposed by different valuable researches presented in the logistic way.

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Lifestyle and Sporadic Colorectal Cancer in India

  • Sinha, Rupal;Doval, Dinesh Chandra;Hussain, Showket;Kumar, Kapil;Singh, Shivendra;Basir, Seemi Farhat;Bharadwaj, Mausumi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7683-7688
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    • 2015
  • Background: The study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population. Materials and Methods: One hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded. Results: The majority of the patients had colonic cancer (68%), advanced tumor stage 3 & 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value <0.001), difficulty in micturition (p-value 0.012) and constipation (p-value 0.007) were found to be statistically significant. Abdominal pain was more frequently reported in patients with metastasis (p-value 0.031). Loss of weight statistically correlated with absence of lymphatic invasion (p-value 0.047). Associations between tumor stage and alcohol intake (p-value 0.050) and non vegetarian diet (p-value 0.006); lymphatic invasion and intake of spicy food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020). Conclusions: Minimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.