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Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or… (More)
The use of patient-specific data in drug and dose selection is becoming an increasingly important component in cancer therapy. Basing drug choice on molecular aspects of the tumor is consistent with the identification of cancer as a molecular disease or diseases, even within the same histological type, and its treatment specific to the background from which… (More)
Reversible changes in gene expression independent of the genetic code can be transmitted from one generation to the next via poorly understood mechanisms. In worms, a histone-modifying enzyme is necessary to keep small RNA-guided transgenerational gene silencing in check.
Germline-expressed endogenous small interfering RNAs (endo-siRNAs) transmit multigenerational epigenetic information to ensure fertility in subsequent generations. In Caenorhabditis elegans, nuclear RNAi ensures robust inheritance of endo-siRNAs and deposition of repressive H3K9me3 marks at target loci. How target silencing is maintained in subsequent… (More)
piRNAs silence foreign genes, such as transposons, to preserve genome integrity, but they also target endogenous mRNAs by mechanisms that are poorly understood. Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway. To assess the dysregulation of gene silencing caused by lack… (More)