Search results for "Pharmacogenomics"
showing 10 items of 53 documents
Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in C…
2017
ABSTRACT Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions. Here we investigated chemoprofiles of three Curcuma species and observed a great variety of phytochemicals with curcumin being among the few present in all three species. On the other hand ascorbic acid (AA) was a compound that was solely found in Curcuma longa. In the present study we explored the cytotoxic effect of a curcumin/AA combination toward human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model. The drug combination showed additive cytotoxicity towards CCRF-CEM and CEM/ADR…
A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests
2021
The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction t…
OSAnalyzer: A Bioinformatics Tool for the Analysis of Gene Polymorphisms Enriched with Clinical Outcomes.
2016
Background: The identification of biomarkers for the estimation of cancer patients’ survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants. Methods: In order to provide support …
TLR2 and age-related diseases: potential effects of Arg753Gln and Arg677Trp polymorphisms in acute myocardial infarction.
2008
ABSTRACT Inflammation is a key component of immune system. It is involved in both defense and pathophysiological events maintaining the dynamic homeostasis of host organism. Its function is controlled by innate immunity genes. Both their polymorphisms and environmental conditions give rise to different phenotypes in human population. Proinflammatory genotype may be beneficial in early life but not in old people. With advancing age, indeed, it increases the vulnerability and the intensity to inflammatory reactions responsible for the chronic inflammatory diseases, such as atherosclerosis and myocardial infarction (MI). Several studies have looked for detecting a genetic risk profile that mig…
Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics.
2008
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory c…
The experience of physicians in pharmacogenomic clinical decision support within eight German university hospitals.
2017
Aim: The aim of this study was to assess the physicians’ attitude, their knowledge and their experience in pharmacogenomic clinical decision support in German hospitals. Materials & methods: We conducted an online survey to address physicians of 13 different medical specialties across eight German university hospitals. In total, 564 returned questionnaires were analyzed. Results: The remaining knowledge gap, the uncertainty of test reimbursement and the physicians’ lack of awareness of existing pharmacogenomic clinical decision support systems (CDSS) are the major barriers for implementing pharmacogenomic CDSS into German hospitals. Furthermore, pharmacogenomic CDSS are most effective …
Alzheimer’s disease and genetics of inflammation: a pharmacogenomic vision
2007
Inflammation plays a key role in Alzheimer disease, and dissecting the genetics of inflammation may provide an answer to the possible treatment. The next-generation therapy is based on a pharmacogenomics that will reconure new approaches to a drug used on definite people with specific dosage. The translation of pharmacogenomics into clinical practice will allow bold steps to be taken toward personalized medicine. In response to tissue injury elicited by trauma or infection, the inflammatory response sets in as a complex network of molecular and cellular interactions, directed to facilitate a return to physiological homeostasis and tissue repair. The role of an individual’s genetic backgroun…
Broad-spectrum Cross-resistance to Anticancer Drugs Mediated by Epidermal Growth Factor Receptor
2019
BACKGROUND The oncogenic role of epidermal growth factor receptor (EGFR) has been intensively studied. However, its emerging role in drug resistance has not been fully addressed. MATERIALS AND METHODS This study systematically investigated the correlation of mRNA and protein expression of EGFR, as well as gene amplification and mutations with the log-transformed half-maximal inhibitory concentration (log10IC50) values obtained from the NCI panel of 60 human tumor cell lines against 83 standard anticancer agents and the top 10 natural cytotoxic products previously screened by us. RESULTS EGFR protein expression, rather than other measurements, was most frequently associated with drug respons…
Pharmacogenomics of Cameroonian traditional herbal medicine for cancer therapy
2011
Abstract Ethnopharmacological relevance A socio-economic burden associated with cancers is reported in Africa. Ethnopharmacological usages such as immune and skin disorders, inflammatory, and others chould be considered when selecting plants used to treat cancer, since these reflect disease states bearing relevance to cancer or a cancer symptoms. Materials and methods Documented compounds of Cameroonian medicinal plants were used as keywords in the National Cancer Institute (NCI) database to establish a library of cytotoxic compounds. Cellular and pharmacogenomic profiling was then performed for the 10 most cytotoxic natural products. By COMPARE and hierarchical cluster analyses, candidate …
Pharmacogenomics: a tool to prevent and cure coronary heart disease.
2007
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- …