A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.

Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-regulated protein that regulates full-length AR and AR variants (ARVs) activity in PrCa. PBK overexpression in aggressive PrCa is associated with early biochemical relapse and poor clinical outcome.

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT).

Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target.

Background: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling.

Methods: Using genome-wide approaches, we interrogated all AR regulated kinases.

Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice.

Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms.

Respiratory distress syndrome due to a novel homozygous ABCA3 mutation in a term neonate.

The authors report, for the first time in the literature, a case of respiratory distress syndrome in a term baby due to homozygosity for a p.Trp308Arg/W308R substitution in the ATP-binding cassette transporter 3. The sequence was confirmed by genetic analysis of the baby and both parents.