MRI characteristics predict risk of pathological upgrade in patients with ISUP grade group 1 prostate cancer.

Objective: This study aims to analyse multiparametric MRI (mpMRI) characteristics of patients diagnosed with ISUP grade group (GG) 1 prostate cancer (PC) on initial target plus systematic MRI/TRUS fusion-guided biopsy and investigate histopathological progression during follow-up.

Methods: A retrospective single-centre cohort analysis was conducted on consecutive patients with mpMRI visible lesions (PI-RADS ≥ 3) and detection of ISUP-1-PC at the time of initial biopsy. The study assessed clinical, mpMRI, and histopathological parameters.

MRI in-bore biopsy following MRI/US fusion-guided biopsy in patients with persistent suspicion of clinically significant prostate cancer.

Purpose: Patients with suspicion of clinically significant prostate cancer (csPC) on multiparametric prostate MRI (mpMRI) but negative or inconclusive MRI/US fusion-guided biopsy (FB) can be challenging in clinical practice. To assess the utility of MRI in-bore biopsy (IB) in patients with discordant imaging and histopathological findings after FB.

Methods: Consecutive patients with Prostate Imaging Reporting and Data System (PI-RADS) category 4 or 5 on mpMRI at 3T after FB without histologically confirmed csPC who underwent IB between 01/2014 and 05/2022, were retrospectively included.

MRI characteristics and oncological follow-up of patients with ISUP grade group 4 or 5 prostate cancer.

Objectives: To analyze multiparametric MRI (mpMRI) characteristics of patients with International Society of Urological Pathology (ISUP) grade group (GG) 4 or 5 prostate cancer (PC) and to correlate MRI parameters with the occurrence of biochemical recurrence (BCR) after radical prostatectomy (RPE).

Methods: In this single-center cohort study consecutive patients with mpMRI and ISUP GG 4 or 5 PC were retrospectively analyzed. Clinical, MR-guided biopsy, and diagnostic mpMRI parameter were assessed.

Multiparametric MRI characteristics of prostatitis and atrophy in the peripheral zone in men without prostate cancer.

Purpose: To analyse multiparametric magnetic resonance imaging (mpMRI) characteristics and appearance of histopathologically proven non-cancerous intraprostatic findings focussing on quantity of prostatitis and atrophy in the peripheral zone.

Method: In this retrospective analysis consecutive patients with mpMRI followed by MRI/TRUS-fusion biopsy comprising targeted (TB) and systematic biopsy (SB) cores without prostate cancer (PC) at histopathology were included. Subgroup analysis was performed in younger men (≤50 years).

A year in review: brain barriers and brain fluids research in 2022.

This aim of this editorial is to highlight progress made in brain barrier and brain fluid research in 2022. It covers studies on the blood-brain, blood-retina and blood-CSF barriers (choroid plexus and meninges), signaling within the neurovascular unit and elements of the brain fluid systems. It further discusses how brain barriers and brain fluid systems are impacted in CNS diseases, their role in disease progression and progress being made in treating such diseases.

Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity.

This editorial highlights advances in brain barrier and brain fluid research in 2021. It covers research on components of the blood-brain barrier, neurovascular unit and brain fluid systems; how brain barriers and brain fluid systems are impacted by neurological disorders and their role in disease progression; and advances in strategies for treating such disorders.

Brain Endothelial Cells: Metabolic Flux and Energy Metabolism.

The neurovascular unit (NVU) consists of multiple cell types including brain endothelial cells, pericytes, astrocytes, and neurons that function collectively to maintain homeostasis within the CNS microenvironment. As the principal barrier-forming component of the NVU, the endothelial cells perform an array of complex functions that require substantial energy resources. The principal metabolic pathways for producing ATP are glycolysis and mitochondrial oxidative phosphorylation.

Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.

This editorial discusses advances in brain barrier and brain fluid research in 2020. Topics include: the cerebral endothelium and the neurovascular unit; the choroid plexus; the meninges; cerebrospinal fluid and the glymphatic system; disease states impacting the brain barriers and brain fluids; drug delivery to the brain. This editorial also highlights the recently completed Fluids Barriers CNS thematic series entitled, 'Advances in in vitro modeling of the blood-brain barrier and neurovascular unit'.

Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors.

Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood-brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood-tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a "whole brain" approach to the treatment of brain tumors might be beneficial.

Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging.

Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. [F]FACH was recently developed and showed very promising preclinical results as a potential positron emission tomography (PET) radiotracer for imaging of MCTs. Given that [F]FACH did not show high blood-brain barrier permeability, the current work is aimed to investigate whether more lipophilic analogs of FACH could improve brain uptake for imaging of gliomas, while retaining binding to MCTs.

This was the year that was: brain barriers and brain fluid research in 2019.

This editorial highlights advances in brain barrier and brain fluid research published in 2019, as well as addressing current controversies and pressing needs. Topics include recent advances related to: the cerebral endothelium and the neurovascular unit; the choroid plexus, arachnoid membrane; cerebrospinal fluid and the glymphatic hypothesis; the impact of disease states on brain barriers and brain fluids; drug delivery to the brain; and translation of preclinical data to the clinic. This editorial also mourns the loss of two important figures in the field, Malcolm B.

Development of Novel Silyl Cyanocinnamic Acid Derivatives as Metabolic Plasticity Inhibitors for Cancer Treatment.

Novel silyl cyanocinnamic acid derivatives have been synthesized and evaluated as potential anticancer agents. In vitro studies reveal that lead derivatives 2a and 2b have enhanced cancer cell proliferation inhibition properties when compared to the parent monocarboxylate transporter (MCT) inhibitor cyano-hydroxycinnamic acid (CHC). Further, candidate compounds exhibit several-fold more potent MCT1 inhibition properties as determined by lactate-uptake studies, and these studies are supported by MCT homology modeling and computational inhibitor-docking studies.

A novel MCT1 and MCT4 dual inhibitor reduces mitochondrial metabolism and inhibits tumour growth of feline oral squamous cell carcinoma.

Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC.

Novel N,N-dialkyl cyanocinnamic acids as monocarboxylate transporter 1 and 4 inhibitors.

Potent and dual monocarboxylate transporter (MCT) 1 and 4 inhibitors have been developed for the first time as potential anticancer agents based on α-cyanocinnamic acid structural template. Candidate inhibitors 1-9 have been evaluated for cell proliferation against MCT1 and MCT4 expressing cancer cell lines. Potential MCT1 and MCT4 binding interactions of the lead compound 9 have been studied through homology modeling and molecular docking prediction.

Development and radiosynthesis of the first F-labeled inhibitor of monocarboxylate transporters (MCTs).

Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers.

The year in review: progress in brain barriers and brain fluid research in 2018.

This editorial focuses on the progress made in brain barrier and brain fluid research in 2018. It highlights some recent advances in knowledge and techniques, as well as prevalent themes and controversies. Areas covered include: modeling, the brain endothelium, the neurovascular unit, the blood-CSF barrier and CSF, drug delivery, fluid movement within the brain, the impact of disease states, and heterogeneity.

Vascular dysfunction-The disregarded partner of Alzheimer's disease.

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology.

mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction.

Mammalian/mechanistic target of rapamycin (mTOR) signaling controls cell growth, proliferation, and metabolism in dividing cells. Less is known regarding its function in postmitotic neurons in the adult brain. Here we created a conditional knockout mouse model to address this question.

Progress in brain barriers and brain fluid research in 2017.

The past year, 2017, has seen many important papers published in the fields covered by Fluids and Barriers of the CNS. This article from the Editors highlights some.

Neurovascular Unit: Basic and Clinical Imaging with Emphasis on Advantages of Ferumoxytol.

Physiological and pathological processes that increase or decrease the central nervous system's need for nutrients and oxygen via changes in local blood supply act primarily at the level of the neurovascular unit (NVU). The NVU consists of endothelial cells, associated blood-brain barrier tight junctions, basal lamina, pericytes, and parenchymal cells, including astrocytes, neurons, and interneurons. Knowledge of the NVU is essential for interpretation of central nervous system physiology and pathology as revealed by conventional and advanced imaging techniques.

Hibernation-based blood loss therapy increases survivability of lethal hemorrhagic shock in rats.

A small-volume (1 ml/kg) resuscitation fluid based on metabolic adaptations in hibernating mammals was optimized using a rat model of hemorrhagic shock. A previous study of this therapy tested only one concentration of three specific components: 4 M D-stereoisomer of beta-hydroxybutyrate (BHB), 43 mM melatonin, and 20% DMSO. In this study, we considered the range of concentrations of BHB and melatonin seen during the physiological extremes of rapid arousal from hypothermic torpor in natural hibernators and applied these to the non-hibernating Sprague-Dawley rat model.

Brain barriers and brain fluid research in 2016: advances, challenges and controversies.

This editorial highlights some of the advances that occurred in relation to brain barriers and brain fluid research in 2016. It also aims to raise some of the attendant controversies and challenges in such research.