Salvage Magnetic Resonance Imaging-guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer.

Background And Objective: Toxicity from local salvage therapy for radiorecurrent prostate cancer (PCa) remains a concern. This phase 2 study evaluates the outcomes of salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA).

Methods: Men with biochemically relapsed, biopsy-proven PCa following definitive radiotherapy underwent whole- or partial-gland sTULSA (NCT03350529).

pSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.

Background: The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3) or serine at 727 (pSTAT3). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway.

Profiling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels: a cross-sectional study.

Background: Bladder cancer is a highly over-represented disease in males. The involvement of sex steroids in bladder carcinogenesis and the utilisation of steroid hormone action as a therapeutic target have been frequently proposed. However, the intratumoural steroid milieu remains unclear.

Lectin-nanoparticle concept for free PSA glycovariant providing superior cancer specificity.

Background: Using lectins to target cancer-associated modifications of PSA glycostructure for identification of clinically significant prostate cancers, e.g., Gleason score (GS) ≥ 7, from benign and indolent cancers (GS 6), is highly promising yet technically challenging.

H-NMR-based urine metabolomics of prostate cancer and benign prostatic hyperplasia.

Background: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are prevalent conditions affecting a significant portion of the male population, particularly with advancing age. Traditional diagnostic methods, such as digital rectal examination (DRE) and prostate-specific antigen (PSA) tests, have limitations in specificity and sensitivity, leading to potential overdiagnosis and unnecessary biopsies.

Significance: This study explores the effectiveness of H NMR urine metabolomics in distinguishing PCa from BPH and in differentiating various PCa grades, presenting a non-invasive diagnostic alternative with the potential to enhance early detection and patient-specific treatment strategies.

PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures.

Gene fusions are common in high-grade serous ovarian cancer (HGSC). Such genetic lesions may promote tumorigenesis, but the pathogenic mechanisms are currently poorly understood. Here, we investigated the role of a PIK3R1-CCDC178 fusion identified from a patient with advanced HGSC.

Intermediate filaments in the heart: The dynamic duo of desmin and lamins orchestrates mechanical force transmission.

The intermediate filament (IF) cytoskeleton supports cellular structural integrity, particularly in response to mechanical stress. The most abundant IF proteins in mature cardiomyocytes are desmin and lamins. The desmin network tethers the contractile apparatus and organelles to the nuclear envelope and the sarcolemma, while lamins, as components of the nuclear lamina, provide structural stability to the nucleus and the genome.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

Purpose: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2).

Methods: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed.

Histological findings in resected leiomyomas following MR-HIFU treatment, single-institution data from seven patients with unfavorable focal therapy.

Purpose: Magnetic resonance - high-intensity focused ultrasound (MR-HIFU) is a noninvasive treatment option for symptomatic uterine leiomyomas. Currently, pretreatment MRI is used to assess tissue characteristics and predict the most likely therapeutic response for individual patients. However, these predictions still entail significant uncertainties.

Prostate cancer detection and segmentation on MRI using non-local mask R-CNN with histopathological ground truth.

Background: Automatic detection and segmentation of intraprostatic lesions (ILs) on preoperative multiparametric-magnetic resonance images (mp-MRI) can improve clinical workflow efficiency and enhance the diagnostic accuracy of prostate cancer and is an essential step in dominant intraprostatic lesion boost.

Purpose: The goal is to improve the detection and segmentation accuracy of 3D ILs in MRI by a proposed a deep learning (DL)-based algorithm with histopathological ground truth.

Methods: This retrospective study included 262 patients with in vivo prostate biparametric MRI (bp-MRI) scans and were divided into three cohorts based on their data analysis and annotation.

STAT5b is a key effector of NRG-1/ERBB4-mediated myocardial growth.

The growth factor Neuregulin-1 (NRG-1) regulates myocardial growth and is currently under clinical investigation as a treatment for heart failure. Here, we demonstrate in several in vitro and in vivo models that STAT5b mediates NRG-1/EBBB4-stimulated cardiomyocyte growth. Genetic and chemical disruption of the NRG-1/ERBB4 pathway reduces STAT5b activation and transcription of STAT5b target genes Igf1, Myc, and Cdkn1a in murine cardiomyocytes.

A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies.

The NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and utilized it to conduct a pan-cancer analysis of oncogenic NRF2 signaling. We identified an immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T cell and macrophage infiltration in squamous malignancies of the lung, head and neck area, cervix and esophagus.

Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress.

The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here, we show that upon HS, lamin A/C was reversibly phosphorylated at serine 22 in concert with HSF1 activation in human cells, mouse cells and Drosophila melanogaster in vivo.

Transcripts of the Prostate Cancer-Associated Gene Are Retained in the Nuclei of Prostatic Epithelial Cells.

Prostate cancer affects millions of men globally. The prostate cancer-associated gene is downregulated in advanced prostate cancer, whereas benign tissue and low-grade cancer display varying expression levels. In this study, we assess the spatial correlation between mRNA and protein using fluorescent in situ hybridization and immunohistochemistry for the detection of mRNA and protein in parallel sections of tissue microarrays prepared from radical prostatectomy samples.

Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.

Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus.

Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques.

Established therapies for prostate cancer (PCa), surgery and radiotherapy, treat the entire gland regardless of the location of the cancerous lesion within the prostate. Although effective, these methods include a significant risk of worsening genitourinary outcomes. Targeted image-guided cancer therapy has gained acceptance through improved PCa detection, localization, and characterization by magnetic resonance imaging (MRI).

PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.

While organ-confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities.

Preclinical Evaluation of Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis.

Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated Zr-labeled bexmarilimab in rabbits.

A heterozygous p.S143P mutation in associates with proteasome dysfunction and enhanced autophagy-mediated degradation of mutant lamins A and C.

Lamins A and C are nuclear intermediate filament proteins that form a proteinaceous meshwork called lamina beneath the inner nuclear membrane. Mutations in the gene encoding lamins A and C cause a heterogenous group of inherited degenerative diseases known as laminopathies. Previous studies have revealed altered cell signaling pathways in lamin-mutant patient cells, but little is known about the fate of mutant lamins A and C within the cells.

Comprehensive genomic profiling of Finnish lung adenocarcinoma cohort reveals high clinical actionability and SMARCA4 altered tumors with variable histology and poor prognosis.

Introduction: Lung adenocarcinoma is the most common type of lung cancer and typically carries a high number of mutations. However, the genetic background of the tumors varies according to patients' ethnic background and smoking status. Little data is available on the mutational landscape and the frequency of actionable genomic alterations in lung adenocarcinoma in the Finnish population.

Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

Background: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.

Objective: To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).

Design, Setting, And Participants: The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.

Value of Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [F]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study.

Objectives: The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).

Methods: This phase I/II study was conducted in 30 biopsy-positive PCa subjects.

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator.

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools.

Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI.