Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence.

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS.

Screening of metabolic modulators identifies new strategies to target metabolic reprogramming in melanoma.

The prognosis of metastatic melanoma remains poor due to de novo or acquired resistance to immune and targeted therapies. Previous studies have shown that melanoma cells have perturbed metabolism and that cellular metabolic pathways represent potential therapeutic targets. To support the discovery of new drug candidates for melanoma, we examined 180 metabolic modulators, including phytochemicals and anti-diabetic compounds, for their growth-inhibitory activities against melanoma cells, alone and in combination with the BRAF inhibitor vemurafenib.

Noninvasive Detection of High Grade Prostate Cancer by DNA Methylation Analysis of Urine Cells Captured by Microfiltration.

Purpose: With the aim of developing a noninvasive test to detect clinically significant prostate cancer we investigated the potential of capturing cells from urine by microfiltration coupled with analysis of DNA methylation biomarkers.

Materials And Methods: In this prospective study urine from men suspected of having prostate cancer who were scheduled for transrectal ultrasound guided biopsy of the prostate was collected before digital rectal examination in 99, after digital rectal examination in 58 and from a urethral catheter in 7. Cells were isolated from whole volume voided urine using a filtration device containing a membrane filter with a pore size of 8 μm.

Inhibition of retinoic acid receptor β signaling confers glycolytic dependence and sensitization to dichloroacetate in melanoma cells.

Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis.

A Prospective Blinded Evaluation of Urine-DNA Testing for Detection of Urothelial Bladder Carcinoma in Patients with Gross Hematuria.

Unlabelled: Retrospective studies have provided proof of principle that bladder cancer can be detected by testing for the presence of tumor DNA in urine. We have conducted a prospective blinded study to determine whether a urine-based DNA test can replace flexible cystoscopy in the initial assessment of gross hematuria. A total of 475 consecutive patients underwent standard urological examination including flexible cystoscopy and computed tomography urography, and provided urine samples immediately before (n=461) and after (n=444) cystoscopy.