• Title/Summary/Keyword: MGMT

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Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Quantitative Analysis for Win/Loss Prediction of 'League of Legends' Utilizing the Deep Neural Network System through Big Data

  • No, Si-Jae;Moon, Yoo-Jin;Hwang, Young-Ho
    • Journal of the Korea Society of Computer and Information
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    • v.26 no.4
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    • pp.213-221
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    • 2021
  • In this paper, we suggest the Deep Neural Network Model System for predicting results of the match of 'League of Legends (LOL).' The model utilized approximately 26,000 matches of the LOL game and Keras of Tensorflow. It performed an accuracy of 93.75% without overfitting disadvantage in predicting the '2020 League of Legends Worlds Championship' utilizing the real data in the middle of the game. It employed functions of Sigmoid, Relu and Logcosh, for better performance. The experiments found that the four variables largely affected the accuracy of predicting the match --- 'Dragon Gap', 'Level Gap', 'Blue Rift Heralds', and 'Tower Kills Gap,' and ordinary users can also use the model to help develop game strategies by focusing on four elements. Furthermore, the model can be applied to predicting the match of E-sports professional leagues around the world and to the useful training indicators for professional teams, contributing to vitalization of E-sports.

Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

  • Zekri, Abd El-Rahman Nabawy;Nassar, Auhood Abdel-Monem;El-Rouby, Mahmoud Nour El-Din;Shousha, Hend Ibrahim;Barakat, Ahmed Barakat;El-Desouky, Eman Desouky;Zayed, Naglaa Ali;Ahmed, Ola Sayed;Youssef, Amira Salah El-Din;Kaseb, Ahmed Omar;El-Aziz, Ashraf Omar Abd;Bahnassy, Abeer Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6721-6726
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    • 2013
  • Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

THE EFFECT OF GENETIC VARIATION IN THE DNA BASE REPAIR GENES ON THE RISK OF HEAD AND NECK CANCER (DNA 염기손상 치유유전자의 변이와 두경부암 발생 위험성)

  • Oh, Jung-Hwan;Yoon, Byung-Wook;Choi, Byung-Jun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.5
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    • pp.509-517
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    • 2008
  • DNA damage accumulates in cells as a result of exposure to exogenous agents such as benzopyrene, cigarette smoke, ultraviolet light, X-ray, and endogenous chemicals including reactive oxygen species produced from normal metabolic byproducts. DNA damage can also occur during aberrant DNA processing reactions such as DNA replication, recombination, and repair. The major of DNA damage affects the primary structure of the double helix; that is, the bases are chemically modified. These modification can disrupt the molecules'regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. DNA repair genes and proteins scan the global genome to detect and remove DNA damage and damage to single nucleotides. Direct reversal of DNA damage, base excision repair, double strand break. DNA repair are known relevant DNA repair mechanisms. Four different mechanisms are distinguished within excision repair: direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Genetic variation in DNA repair genes can modulate DNA repair capacity and alter cancer risk. The instability of a cell to properly regulate its proliferation in the presence of DNA damage increase risk of gene mutation and carcinogenesis. This article aimed to review mechanism of excision repair and to understand the relationship between genetic variation of excision repair genes and head and neck cancer.

Added Value of Contrast Leakage Information over the CBV Value of DSC Perfusion MRI to Differentiate between Pseudoprogression and True Progression after Concurrent Chemoradiotherapy in Glioblastoma Patients

  • Pak, Elena;Choi, Seung Hong;Park, Chul-Kee;Kim, Tae Min;Park, Sung-Hye;Won, Jae-Kyung;Lee, Joo Ho;Lee, Soon-Tae;Hwang, Inpyeong;Yoo, Roh-Eul;Kang, Koung Mi;Yun, Tae Jin
    • Investigative Magnetic Resonance Imaging
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    • v.26 no.1
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    • pp.10-19
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    • 2022
  • Purpose: To evaluate whether the added value of contrast leakage information from dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) is a better prognostic imaging biomarker than the cerebral blood volume (CBV) value in distinguishing true progression from pseudoprogression in glioblastoma patients. Materials and Methods: Forty-nine glioblastoma patients who had undergone MRI after concurrent chemoradiotherapy with temozolomide were enrolled in this retrospective study. Twenty features were extracted from the normalized relative CBV (nCBV) and extraction fraction (EF) map of the contrast-enhancing region in each patient. After univariable analysis, we used multivariable stepwise logistic regression analysis to identify significant predictors for differentiating between pseudoprogression and true progression. Receiver operating characteristic (ROC) analysis was employed to determine the best cutoff values for the nCBV and EF features. Finally, leave-one-out cross-validation was used to validate the best predictor in differentiating between true progression and pseudoprogression. Results: Multivariable stepwise logistic regression analysis showed that MGMT (O6-methylguanine-DNA methyltransferase) and EF max were independent differentiating variables (P = 0.004 and P = 0.02, respectively). ROC analysis yielded the best cutoff value of 95.75 for the EF max value for differentiating the two groups (sensitivity, 61%; specificity, 84.6%; AUC, 0.681 ± 0.08; 95% CI, 0.524-0.837; P = 0.03). In the leave-one-out cross-validation of the EF max value, the cross-validated values for predicting true progression and pseudoprogression accuracies were 69.4% and 71.4%, respectively. Conclusion: We demonstrated that contrast leakage information parameter from DSC MRI showed significance in differentiating true progression from pseudoprogression in glioblastoma patients.

Food Components Characteristic of Oysters Produced in Korea (국내 산지별 굴의 성분 특성)

  • Choi, Jong-Duck;Hwang, Seok-Min;Kang, Jin-Young;Kim, Sang-Hyun;Kim, Jeong-Gyun;Oh, Kwang-Soo
    • Journal of agriculture & life science
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    • v.46 no.6
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    • pp.105-115
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    • 2012
  • The detailed proximate, fatty/amino acid, mineral composition, texture, color, chemical and taste compounds of six oysters (four kinds of cultured oysters and two kinds of wild oysters) in Korea were investigated. Length and weight of the shell removed cultured and wild oysters were 4.7~5.1 and 3.0~4.2 cm, and 5.9~9.1 and 2.6~5.5 g, respectively. The proximate compositions were not significantly different between cultured and wild oysters. Amino nitrogen and volatile basic nitrogen content of these ones were 232.8~258.2 and 160.5~213.9 mg/100 g, 9.5~12.0 and 7.8~9.5 mg/100 g, respectively. As a texture characteristic of muscle, shearing force were 95~114 and 105~132 g. Amounts of total amino acids of cultured and wild oysters were 9,004~10,198 and 8,165~8,942 mg/100 g, respectively. Major amino acids and inorganic ions were aspartic acid, glutamic acid, proline, alanine, leucine, phenylalanine, lysine, arginine and K, Na, Ca, Fe, S, P, Zn. Major fatty acids of these ones were 16:0, 18:0, 16:1n-9, 18:1n-9, 22:1n-9, 16:4n-3, 20:5n-3 and 22:6n-3, and there was little difference between the two groups. Amounts of free amino acids of cultured and wild oysters extracts were 1,444~1,620 and 1,017~1,277 mg/100 g, respectively, and major ones were taurine, glutamic acid, glycine, alanine, tryptophan, ornithine and lysine. There is a little difference in glycine, tryptophan, ornithine and arginine contents, but TMAO and TMA contents were low in amount, and were not significantly different between the two groups.