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      • SCIESCOPUSKCI등재

        Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation

        ( Gilbert J. Burckart ),( Felix W. Frueh ),( Lawrence J. Lesko ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.1

        The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of supporting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.

      • Epigenetic Changes in Gene Expression for Drug-Metabolizing Enzymes and Transporters

        Kim, In-Wha,Han, Nayoung,Burckart, Gilbert J.,Oh, Jung Mi Wiley (John WileySons) 2014 Pharmacotherapy Vol.34 No.2

        <P>Individual differences in drug response can be caused by genetic and epigenetic variability and disease determinants. Pharmacoepigenetics is a new field that studies the expression changes in pharmacogenes without changes in DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modification, small noncoding RNAs, and nucleosome remodeling. Researchers are actively attempting to identify epigenetic mechanisms for controlling the expression of enzymes and transporters affecting the metabolism and disposition of drugs. Current evidence suggests that epigenetic changes play a major role in cytochrome P450 enzyme expression, major transporter function, and in interactions with nuclear receptors. A thorough understanding of pharmacoepigenetics provides insight into new approaches to drug discovery and development, provides an understanding of previously observed actions of older drugs, and provides a pathway by which epigenetics can be harnessed to provide better patient-specific therapy.</P>

      • SCIESCOPUSKCI등재

        Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation

        Frueh, Felix W.,Lesko, Lawrence J.,Burckart, Gilbert J. The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.

        The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of sup-porting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.

      • SCIESCOPUSKCI등재

        Regulation of Pharmacogene Expression by microRNA in The Cancer Genome Atlas (TCGA) Research Network

        Han, Nayoung,Song, Yun-Kyoung,Burckart, Gilbert J.,Ji, Eunhee,Kim, In-Wha,Oh, Jung Mi The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.5

        Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.

      • SCIESCOPUSKCI등재

        Regulation of Pharmacogene Expression by microRNA in The Cancer Genome Atlas (TCGA) Research Network

        ( Nayoung Han ),( Yun-kyoung Song ),( Gilbert J. Burckart ),( Eunhee Ji ),( In-wha Kim ),( Jung Mi Oh ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.5

        Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.

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