The Emerging Predictive and Prognostic Role of Aggressive-Variant-Associated Tumor Suppressor Genes Across Prostate Cancer Stages.

Aggressive variant prostate cancer (AVPC) is characterized by a molecular signature involving combined defects in , , and/or (AVPC-TSGs), identifiable through immunohistochemistry or genomic analysis. The reported prevalence of AVPC-TSG alterations varies widely, reflecting differences in assay sensitivity, treatment pressure, and disease stage evolution. Although robust clinical evidence is still emerging, the study of AVPC-TSG alterations in prostate cancer (PCa) is promising.

Discovery of UCB9386: A Potent, Selective, and Brain-Penetrant Nuak1 Inhibitor Suitable for Pharmacological Studies.

Nuak1 (NUAK family SnF1-like kinase-1) is a serine-threonine kinase and a member of the AMPK family. Interest in Nuak1 has increased over the years due to the role it plays in several biological processes, from tumor cell invasion and proliferation to Tau stabilization. Nuak1 is expressed in many cancer cell lines and many reports describe this target as an oncogene, the inhibition of which is hypothesized to be valuable for treating various cancer types including glioma.

Synthetic DNA-based Swimmers Driven by Enzyme Catalysis.

Here, we report DNA-based synthetic nanostructures decorated with enzymes (hereafter referred to as DNA-enzyme swimmers) that self-propel by converting the enzymatic substrate to the product in solution. The DNA-enzyme swimmers are obtained from tubular DNA structures that self-assemble spontaneously by the hybridization of DNA tiles. We functionalize these DNA structures with two different enzymes, urease and catalase, and show that they exhibit concentration-dependent movement and enhanced diffusion upon addition of the enzymatic substrate (i.

Stock profiling using time-frequency-varying systematic risk measure.

This study proposes a wavelets approach to estimating time-frequency-varying betas in the capital asset pricing model (CAPM) framework. The dynamic of systematic risk across time and frequency is analyzed to investigate stock risk-profile robustness. Furthermore, we emphasize the effect of an investor's investment horizon on the robustness of portfolio characteristics.

Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

Background: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking.

Percutaneous Intervention With GuideLiner Catheter in 4 Patients With Anomalous Coronary Artery Originating From Opposite Sinus of Valsalva.

Percutaneous intervention in anomalous coronary arteries originating from the opposite sinus of Valsalva is complicated by their unusual location and course, which makes selective cannulation difficult. The GuideLiner (Vascular Solutions, Inc.) is a monorail guide extension catheter designed to advance beyond the tip of a mother guide catheter to enable deep intubation of a coronary artery, provide extra support, and improve coaxial alignment.

Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.

Background: STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival.

Methods: Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy.

Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity.

Malaria remains a prevalent infectious disease in developing countries. The first-line therapeutic options are based on combinations of fast-acting artemisinin derivatives and longer-acting synthetic drugs. However, the emergence of resistance to these first-line treatments represents a serious risk, and the discovery of new effective drugs is urgently required.

Engineering transient dynamics of artificial cells by stochastic distribution of enzymes.

Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior.

Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.

The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice.

3D-bioengineered model of human skeletal muscle tissue with phenotypic features of aging for drug testing purposes.

Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics.

Biohybrid soft robots with self-stimulating skeletons.

Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers).

Biohybrid robotics: From the nanoscale to the macroscale.

Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems.

Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer.

Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH.

Current evidence between hospital volume and perioperative outcome: Prospective assessment of robotic radical prostatectomy safety profile in a regional center of medium annual caseload.

Introduction: We aimed to present the safety profile of robotic radical prostatectomy (RARP) performed in a single center of medium surgical volume since its introduction and identify predictors of postoperative complications.

Methods: We prospectively collected clinical data from 317 consecutive patients undergoing RARP between August 2011 and November 2019 in a medium-volume center. Surgical procedures were performed by a single experienced surgeon.

Ionic Species Affect the Self-Propulsion of Urease-Powered Micromotors.

Enzyme-powered motors self-propel through the catalysis of bioavailable fuels, which makes them excellent candidates for biomedical applications. However, fundamental issues like their motion in biological fluids and the understanding of the propulsion mechanism are critical aspects to be tackled before a future application in biomedicine. Herein, we investigated the physicochemical effects of ionic species on the self-propulsion of urease-powered micromotors.

Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial).

Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies.

Fundamental Aspects of Enzyme-Powered Micro- and Nanoswimmers.

Self-propulsion at the nanoscale constitutes a challenge due to the need for overcoming viscous forces and Brownian motion. Inspired by nature, artificial micro- and nanomachines powered by catalytic reactions have been developed. Due to the toxicity of the most commonly used fuels, enzyme catalysis has emerged as a versatile and biocompatible alternative to generate self-propulsion.

Noncontinuous Super-Diffusive Dynamics of a Light-Activated Nanobottle Motor.

We report a carbonaceous nanobottle (CNB) motor for near infrared (NIR) light-driven jet propulsion. The bottle structure of the CNB motor is fabricated by soft-template-based polymerization. Upon illumination with NIR light, the photothermal effect of the CNB motor carbon shell causes a rapid increase in the temperature of the water inside the nanobottle and thus the ejection of the heated fluid from the open neck, which propels the CNB motor.

Miniaturized soft bio-hybrid robotics: a step forward into healthcare applications.

Soft robotics is an emerging discipline that employs soft flexible materials such as fluids, gels and elastomers in order to enhance the use of robotics in healthcare applications. Compared to their rigid counterparts, soft robotic systems have flexible and rheological properties that are closely related to biological systems, thus allowing the development of adaptive and flexible interactions with complex dynamic environments. With new technologies arising in bioengineering, the integration of living cells into soft robotic systems offers the possibility of accomplishing multiple complex functions such as sensing and actuating upon external stimuli.