Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer.
We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (
Authors: Miranti CK, Moore S, Kim Y, Chappeta VR, Wu K, De B, Gokhale V, Hurley LH, Reyes-Reyes EM Abstract The androgen receptor (AR) is a major driver of prostate cancer development and progression. Men who develop advanced prostate cancer often have long-term cancer control when treated with androgen-deprivation therapies (ADT). Still, their disease inevitably becomes resistant to ADT and progresses to castration-resistant prostate cancer (CRPC). ADT involves potent competitive AR antagonists and androgen synthesis inhibitors. Resistance to these types of treatments emerges, primarily through the maintenance of ...
ConclusionThere is an acute worsening of urinary symptoms among men receiving modern post-prostatectomy radiation. Worsening of urgency is associated with bladder dosimetry while flow, frequency, nocturia, and dysuria are not. This data can be used during treatment planning to reduce acute urinary toxicity during post-prostatectomy radiation.
PROSTATE cancer has overtaken breast cancer to become the UK's most commonly diagnosed form of the disease. The development comes 10 years earlier than predicted after cases more than doubled in the past two decades, said Prostate Cancer UK.
Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.9b02008
Ground-breaking research, together with greater awareness - highlighted by the Daily Mail's End The Needless Prostate Deaths campaign - is changing the outlook for men with the condition.
MCL1 has critical antiapoptotic functions and its levels are tightly regulated by ubiquitylation and degradation, but mechanisms that drive this degradation, particularly in solid tumors, remain to be established. We show here in prostate cancer cells that increased NOXA, mediated by kinase inhibitor activation of an integrated stress response, drives the degradation of MCL1, and identify the mitochondria-associated ubiquitin ligase MARCH5 as the primary mediator of this NOXA-dependent MCL1 degradation. Therapies that enhance MARCH5-mediated MCL1 degradation markedly enhance apoptosis in response to a BH3 mimetic agent tar...
AbstractPurposeWe evaluated efficacy and safety profile of patients with anticoagulation therapy (AT) undergoing holmium laser enucleation of the prostate (HoLEP).MethodsWithin our prospective institutional database (11/2017 to 11/2019), we analyzed functional outcomes and 30-day complication rates of HoLEP patients according to Clavien –Dindo classification (CLD), stratified according to specific AT vs. no AT. Further analyses consisted of uni- and multivariate logistic regression models (LRM) predicting complications.ResultsOf 268 patients undergoing HoLEP, 104 (38.8%) received AT: 25.7% were treated with platelet ...
ConclusionsLaparo-endoscopic inguinal hernia mesh repair has a significant impact on performing a radical prostatectomy and PLND. Surgeons should postpone the inguinal hernia repair of patients in the workup for a radical prostatectomy, with the preferable option of performing the radical prostatectomy and inguinal hernia repair in the same procedure. Alternatively, a Lichtenstein repair can be performed.
Volume 9, Issue 1, January 2020 .
ConclusionFocal ablation using IRE for PCa in the distal apex appears safe and feasible with acceptable early QoL and oncologic outcomes.