The economic costs of precision medicine for clinical translational research among children with high-risk cancer.

Embedding precision medicine in paediatric oncology shows promise to have a positive impact on how children with cancer will be treated in the future. While there are a number of studies of precision medicine in childhood cancer, there is limited evidence available on the cost of implementing the related testing. This is the first Australian study that systematically measures the cost of using precision medicine in the care of high-risk childhood cancers, through the Zero Childhood Cancer Precision Medicine Programme.

SNP rs16906252C>T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer.

Purpose: Methylation of the MGMT promoter is the major cause of O-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues.

Experimental Design: By applying a molecular pathologic epidemiology case-control study design, associations between rs16906252C>T and risk for colorectal cancer overall, and colorectal cancer stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of colorectal cancer cases and controls.

The chemopreventive activity of the butyric acid prodrug tributyrin in experimental rat hepatocarcinogenesis is associated with p53 acetylation and activation of the p53 apoptotic signaling pathway.

The reversibility of non-genotoxic phenotypic alterations has been explored in order to develop novel preventive and therapeutic approaches for cancer control. Previously, it has been demonstrated that histone deacetylase (HDAC) inhibitor tributyrin, a butyric acid prodrug, to have chemopreventive effects on rat hepatocarcinogenesis. The goal of this study was to determine molecular mechanisms associated with the chemopreventive activity of tributyrin.

Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis.

The chemopreventive effects of tributyrin (TB) and vitamin A (VA), alone or in combination, were investigated during the promotion phase of rat hepatocarcinogenesis. Compared to diethylnitrosamine control rats, TB and TB+VA-treated rats, but not VA-treated rats, presented a lower incidence and mean number of hepatocyte nodules and a smaller size of persistent preneoplastic lesions (pPNLs). In addition, TB and TB+VA-treated rats exhibited a higher apoptotic body index in pPNL and remodeling PNL, whereas VA-treated rats presented only a higher apoptotic body index in remodeling PNL.

Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: efficacy of tributyrin, a butyric acid prodrug.

Hepatocellular carcinoma (HCC) ranks in prevalence and mortality among top 10 cancers worldwide. Butyric acid (BA), a member of histone deacetylase inhibitors (HDACi) has been proposed as an anticarcinogenic agent. However, its short half-life is a therapeutical limitation.