Strategies for Improving Care of Patients with Acute Kidney Injury Requiring Dialysis (AKI-D) in the Outpatient Hemodialysis Setting.

Patients with acute kidney injury often require dialysis (AKI-D) in the outpatient setting following hospitalization. Management of the patient with AKI-D should focus on preventing further insult to the damaged kidney and recovery of kidney function. Clinical attention should include continuity of care, education, infection control, medication management, and fluid management.

Stable oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast cancer.

With the recent comprehensive mapping of cancer genomes, there is now a need for functional approaches to edit the aberrant epigenetic state of key cancer drivers to reprogram the epi-pathology of the disease. In this study we utilized a programmable DNA-binding methyltransferase to induce targeted incorporation of DNA methylation (DNAme) in the SOX2 oncogene in breast cancer through a six zinc finger (ZF) protein linked to DNA methyltransferase 3A (ZF-DNMT3A). We demonstrated long-lasting oncogenic repression, which was maintained even after suppression of ZF-DNMT3A expression in tumor cells.

Dysregulation of the epigenome in human breast cancer: contributions of gene-specific DNA hypermethylation to breast cancer pathobiology and targeting the breast cancer methylome for improved therapy.

Triple-negative breast cancers (including basal-like and claudin-low molecular subtypes) represent 20% to 25% of all breast cancers, but disproportionately contribute to breast cancer-associated death. We have identified a novel fundamental biological property of triple-negative breast cancers: most triple-negative breast cancers express aberrant DNA hypermethylation due to overexpression of DNA methyltransferase 3b (and hyperactivity of the DNA methyltransferase enzymes). DNA methyltransferase 3b overexpression occurs secondary to loss of miRNA-mediated post-transcriptional regulation.

Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer.

Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation.

Dysregulation of the epigenome in triple-negative breast cancers: basal-like and claudin-low breast cancers express aberrant DNA hypermethylation.

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers.