LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression

Бузук Георгий Николаевич

юбилеиученыеВРАЧ

Increased CK5/CK8-Positive Intermediate Cells with Stromal Smooth Muscle Cell Atrophy in the Mice Lacking Prostate Epithelial Androgen Receptor

Results from tissue recombination experiments documented well that stromal androgen receptor (AR) plays essential roles in prostate development, but epithelial AR has little roles in prostate development. Using cell specific knockout AR strategy, we generated pes-ARKO mouse with knock out of AR only in the prostate epithelial cells and demonstrated that epithelial AR might also play important roles in the development of prostate gland. We found mice lacking the prostate epithelial AR have increased apoptosis in epithelial CK8-positive luminal cells and increased proliferation in epithelial CK5-positive basal cells. The consequences of these two contrasting results could then lead to the expansion of CK5/CK8-positive intermediate cells, accompanied by stromal atrophy and impaired ductal morphogenesis. Molecular mechanism dissection found AR target gene, TGF-β1, might play important roles in this epithelial AR-to-stromal morphogenesis modulation. Collectively, these results provided novel information relevant to epithelial AR functions in epithelial-stromal interactions during the development of normal prostate, and suggested AR could also function as suppressor in selective cells within prostate

Isotactic-Polypropylene/Atactic-Polystyrene Miktoarm Star Copolymers: Synthesis and Aggregation Morphology

In this work, a series of isotactic-polypropylene/atactic-polystyrene (iPP/aPS) miktoarm star copolymers, PxSy, was synthesized via an arm-first approach. Varied star macromolecule architectures were fabricated by designing the arm length and the arm numbers (x and y). These miktoarm stars were able to form micelles in selective solvent (N,N′-dimethylformamide (DMF)), in which the insoluble iPP arms formed the core and the soluble aPS arms formed the shell. The miktoarm polymers aggregated to micro-nanoscale binary structures (MNBSes) in the casting process, and their morphologies, including the MNBS shape and size, were greatly influenced by the PxSy architectures. The MNBSes endowed the material surface with superhydrophobic performance with a water contact angle of 157.0° and a sliding angle of 1.5°

Hem-o-lok-free and Retzius-sparing robot-assisted laparoscopic radical prostatectomy with retrograde release of the neurovascular bundle

Abstract. Background:. Robot-assisted laparoscopic radical prostatectomy (RARP) has gradually become the standard surgical procedure for prostate cancer. This video aimed to demonstrate a new and improved surgical approach for prostate cancer that passes through the pouch of Douglas and allows retrograde release of the neurovascular bundle (NVB). The technique is Hem-o-lok-free and Retzius-sparing and is performed without opening the pelvic floor fascia during RARP. Methods:. A 69-year-old man was diagnosed with prostate cancer (clinical stage T2bN0M0). We followed the process of Retzius-sparing RARP [published by Galfano et al. in 2013] and did some modification. The critical technical points associated with this technique included locating the fascial layer at the prostatic apex and performing complete retrograde release of the NVB along the anatomical structure. We used diathermy to perform precision hemostasis on large vessels, especially those around the basal part of prostate, with relatively less damage. In addition, Hem-o-lok was not used in this procedure. Results:. Negative surgical margin and stage T2bN0M0 were confirmed. Continence was achieved immediately after cathter removal. One month after surgery, prostate specific antigen was undetectable. Erectile function was preserved 3 months postoperatively. Conclusions:. Hem-o-lok-free and Retzius-sparing RARP is a feasible surgical approach that combines the benefits of complete retrograde release of the NVB, preserving the nerves and vascular structures around the prostate, protecting the pelvic floor structure, and ensuring rapid recovery of micturition control

Correction: A-Methylacyl-CoA Racemase (AMACR) and Prostate-Cancer Risk: A Meta-Analysis of 4,385 Participants.

[This corrects the article DOI: 10.1371/journal.pone.0074386.]

Joint Intra/Inter-Slot Code Design for Unsourced Multiple Access in 6G Internet of Things

Unsourced multiple access (UMA) is the technology for massive, low-power, and uncoordinated Internet-of-Things in the 6G wireless system, improving connectivity and energy efficiency on guaranteed reliability. The multi-user coding scheme design is a critical problem for UMA. This paper proposes a UMA coding scheme based on the T-Fold IRSA (irregular repetition slotted Aloha) paradigm by using joint Intra/inter-slot code design and optimization. Our scheme adopts interleave-division multiple access (IDMA) to enhance the intra-slot coding gain and the low-complexity joint intra/inter-slot SIC (successive interference cancellation) decoder structure to recover multi-user payloads. Based on the error event decomposition and density evolution analysis, we build a joint intra/inter-slot coding parameter optimization algorithm to minimize the SNR (signal-to-noise ratio) requirement at an expected system packet loss rate. Numerical results indicate that the proposed scheme achieves energy efficiency gain by balancing the intra/inter-slot coding gain while maintaining relatively low implementation complexity