• 제목/요약/키워드: MGMT

검색결과 46건 처리시간 0.016초

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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    • 제32권3호
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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
    • 한국컴퓨터정보학회논문지
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    • 제26권4호
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    • pp.213-221
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    • 2021
  • 이 논문은 League of Legends (LOL) 게임의 승패를 예측하기 위하여 Deep Neural Network Model 시스템을 제안한다. 이 모델은 다양한 LOL 빅데이터를 활용하여 TensorFlow 의 Keras에 의하여 설계하였다. 연구 방법으로 한국 서버의 챌린저 리그에서 행해진 약 26000 경기 데이터 셋을 분석하여, 경기 도중 데이터를 수집하여 그 중에서 드래곤 처치 수, 챔피언 레벨, 정령, 타워 처치 수가 게임 결과에 유의미한 영향을 끼치는 것을 확인하였다. 이 모델은 Sigmoid, ReLu 와 Logcosh 함수를 사용했을 때 더 높은 정확도를 얻을 수 있었다. 실제 LOL의 프로 게임 16경기를 예측한 결과 93.75%의 정확도를 도출했다. 게임 평균시간이 34분인 것을 고려하였을 때, 게임 중반 15분 정도에 게임의 승패를 예측할 수 있음이 증명되었다. 본 논문에서 설계한 이 프로그램은 전 세계 E-sports 프로리그의 활성화, 승패예측과 프로팀의 유용한 훈련지표로 활용 가능하다고 사료된다.

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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    • 제14권11호
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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.

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

  • 오정환;윤병욱;최병준
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제34권5호
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    • pp.509-517
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    • 2008
  • DNA 손상 치유 유전자 연구를 기초로 한 임상적 접근이 새로운 치료방법으로 떠오르고 있다. 많은 연구들이 중요한 DNA 수복유전자의 다형성을 찾아내어 각각의 단백질의 활동성에 대한 영향을 알아내고 특정한 치료법을 찾아내고 임상적 적용을 시도하고 결과를 평가하였다. 그 결과 암 치료에서 정상 세포와 암세포에서 DNA 수복 유전자의 발현 분석은 화학요법이나 방사선 치료에서 개인맞춤형 치료법을 가능하게 하고 있다. 예를 들어, NER이 결핍된 종양은 cisplatin 치료에 민감성을 나타내고, MMR 결핍세포는 알킬화 화학요법 약제에 높은 내성을 나타낸다. 선천성 비폴립성 결장암과 같은 MMR 결손종양 또한 알킬화 화학요법 약제에 의한 치료에 내성을 가진다. 신경교종(glioma)에서 MGMT 유전자 프로모터가 흔히 메틸화되는데 이것은 유전자 발현이 억제되고 알킬화 화학요법제에 대한 반응성을 증가시킨다. 향후 구강악안면외과 영역에서도 구강암의 발생의 위험성을 증가시킬 수 있는 더 많은 DNA 수복 유전자의 다형성을 발굴하고 임상적으로 개인맞춤형 치료법을 개발하고 적용할 수 있는 많은 연구가 필요할 것으로 사료된다.

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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    • 제26권1호
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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.

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

  • 최종덕;황석민;강진영;김상현;김정균;오광수
    • 농업생명과학연구
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    • 제46권6호
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    • pp.105-115
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    • 2012
  • 국내산 양식 및 천연산 굴의 가치 증진 및 보다 효율적인 활용을 위한 식품학적 자료를 얻기 위해 통영, 고성, 여수 및 사천만에서 수하식 및 반수하식으로 양식한 참굴 4종과 고흥, 서천의 해안가 조간대에 서식하는 천연산 참굴류 2종을 구입하여 이들의 영양성분과 풍미성분 조성을 분석 비교하였다. 탈각한 양식산 및 천연산 굴의 크기는 각각 길이 4.7~5.1 및 3.0~4.2 cm, 무게 5.9~9.1 및 2.6~5.5 g으로 산지에 따라 약간 차이가 있었으나, 일반성분 조성의 차이는 거의 없었다. 아미노질소 및 휘발성염기질소 함량은 각각 232.8~258.2 및 160.5~213.9 mg/100 g, 9.5~12.0 및 7.8~9.5 mg/100 g으로 산지에 따라 약간의 차이를 나타내어 맛과 냄새의 강도가 다소 차이가 있음을 확인하였다. 염도는 각각 1.5~1.7 및 1.5~1.8%, 절단력은 95~114 및 105~132 g으로 산지에 따른 차이는 거의 없었다. 양식산과 천연산 굴의 주요 구성지방산은 16:0, 18:0, 16:1n-9, 18:1n-9, 22:1n-9, 16:4n-3, 20:5n-3, 22:6n-3 등으로 산지에 따른 특별한 조성의 차이는 없었다. 총아미노산의 함량은 각각 9,004~10,198 및 8,165~8,942 mg/100 g으로 aspartic acid, glutamic acid, proline, alanine, leucine, phenylalanine, lysine 및 arginine이 주요 구성 아미노산이었고, 주요 무기이온은 K, Na, Ca, Fe, S, P 및 Zn 등으로 산지에 따라 차이를 보였다. 정미발현성분인 유리아미노산의 총함량은 각각 1,444~1,620 및 1,017~1,277 mg/100 g으로 taurine, glutamic acid, glycine, alanine, tryptophan, ornithin 및 lysine 등이 주요 유리아미노산이었으며, 산지에 따라 다소간의 차이를 나타내었다.