Term
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Definition
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Term
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Definition
| microscopic DNA spots (or probes) attached to a solid surface (glass slide); high-throughput screening, measure the expression levels of large numbers of genes |
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Term
| DNA microarray analysis for cancer |
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Definition
| it is the analysis of tumor vs adjacent normal tissue |
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Term
| what are the gene expression differences when you over-express cells with gene X |
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Definition
| gene X vs. its plasmid control vector |
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Term
| What are the gene expression differences when you over-express cells with agent X? |
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Definition
| agent X vs. liquid the agent is dissolved in (termed ‘vehicle’) |
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Definition
| Refers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects |
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Term
| single nucleotide polymorphisms (SNPs) |
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Definition
| single base pair change and they may result in a change of a single amino acid within the coded protein |
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Term
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Definition
| does not change protein sequence but there is a change in the THIRD nucleotide |
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Term
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Definition
| change in protein may significantly impact protein function, there is a change in the SECOND nucleotide |
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Term
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Definition
| may be small or large, single base pair change causes a frame shift in the coding region, almost always results in significant alterations in or loss of activity and encompasses 'copy number varients' (CNVs) |
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Term
| Polymorphism/SNP detection |
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Definition
| PCR & restriction fragment length polymorphism(RFLP)analysis; Sequencing; Real-time PCR; Array-based assays; Genome-wide association studies (GWAS); Next-Generation (‘Next-Gen’) sequencing |
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Term
| Uridinediphosphate glucuronosyltransferase (UGT1A1) |
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Definition
| Phase II detoxification enzyme; Glucuronidates many xenobiotics & endogenous substrates; UDP-glucuronic acid as co-substrate |
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Term
| Polymorphism in UGT1A1 promoter designated UGT1A1*28 |
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Definition
| Causative mutation in Gilbert’s syndrome; TA repeats in TATA box increases from 5 to 8 in *28; Decreased transcription from UGT1A1*28 promoter; Associated with decreased glucuronidation activities; Jaundice from decreased billirubin glucuronidation activity |
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Term
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Definition
| WBCs, buccal cells from cheek swabs, tissue samples from surgery |
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Term
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Definition
| must express gene(s) of interest, RNAses may be presence and splicing varients |
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Term
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Definition
| "housekeeping gene," DNA contamination of RNA and vice versa |
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Term
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Definition
| binds to estrogen receptor that blocks estrogen which is used in breast cancer |
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Term
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Definition
| prevents CYP19 from converting testosterone androstenedione to estrone estradiol; used for breast cancer |
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Term
| Therapeutic efficacy of TAM |
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Definition
those that take it for 5 years exhibit a 30-50% reduction in both the rate of disease
recurrence after 10 years of patient follow-up, and in the occurrence of
contralateral breast cancer |
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Term
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Definition
| hot flashes (severe), endometrial cancer, thrombosis |
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Term
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Definition
| osteoporosis & bone fractures(decreased bone density), hot flashes, altered lipid profiles |
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Term
| TAM vs AI Pharmacogenetics |
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Definition
| targeted interventions for individualized cancer prevention and treatment; focus on metabolism of TAM and exemestane |
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Term
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Definition
| metabolite of tamoxifen that is active against breast cancer |
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Term
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Definition
| enzymes needed for the conversion of tamoxifen to its active metabolite endoxifen |
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Term
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Definition
| Phase I enzyme, hydroxylates variety of substrates; Important in the metabolism of a variety of drugs; Exhibits several polymorphic alleles, several of which have been linked to altered CYP2D6 expression or activity; Whole-gene deletion: 5% allelic prevalence |
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Term
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Definition
| major phase II metabolism pathway; increases water solubility for excretion; inactivation of agent; mainly hepatic, though some UGT enzymes found in extra-hepatic tissues including brease |
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Term
| working hypothesis for anti-breast cancer agents |
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Definition
| Altered patterns of glucuronidation of primary TAM metabolites contribute to inter-individual variability in patient response to TAM |
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Term
| UDP glucuronosyltransferases (UGTs) |
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Definition
| endogenous compounds, exogenous compounds |
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Term
| endogenous compounds broken down by UGT |
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Definition
| C18 and C19 steroids, bilirubin |
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Term
| Exogenous compounds broken down by UGTs |
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Definition
| drugs(eg, acetomeniphen, ibuprofen, morphine); carcinogens (PAHs, nitrosamines, heterocyclic amines); chemotherapeutic/preventive agents(eg, irinotecan, tamoxifen) |
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Term
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Definition
| how genetic makeup of an individual affects his/her response to drugs |
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Term
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Definition
| refers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects |
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Term
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Definition
| ensure maximum efficacy with minimal adverse events |
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Term
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Definition
| examine genetic variations against phenotype or disease symptom |
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Term
| gene regulation: epigenetic differences |
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Definition
| occurs at DNA level, example is methylation events |
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Term
| gene regulation: transcription alerations |
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Definition
| causes differences expression of mRNA |
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Term
| gene regulation: alternate splicing |
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Definition
| result in alterations of mRNA species |
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Term
| gene regulation: microRNA |
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Definition
| regulate the exression of mRNA species that code for proteins |
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Term
| gene regulation: translations |
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Definition
| translating messanger RNA into protiens |
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Term
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Definition
| extracellular signaling by cell-surface receptors or intracellular signaling by nuclear receptors |
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Term
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Definition
| inhibition of cell-cycle progression/ checkpoints and apoptosis |
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Term
| DNA replication and DNA repair |
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Definition
| control by checkpoint and blocking re-replication, maintenance of genomic stability |
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Term
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Definition
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Term
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Definition
| transporters that move compounds into and out of hepatic cell |
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Definition
| enzymes that gets rid of Bilirubin and if you do not get rid of it effectively |
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Term
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Definition
| major metabolite of exemestane; their goal was to try to see if this metabolite was active (meaning it is also an aromatase inhibitor) |
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