IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.

Background: Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results: Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression.

Imaging Spectrum of the Developing Glioblastoma: A Cross-Sectional Observation Study.

Glioblastoma (GBM) has the typical radiological appearance (TRA) of a centrally necrotic, peripherally enhancing tumor with surrounding edema. The objective of this study was to determine whether the developing GBM displays a spectrum of imaging changes detectable on routine clinical imaging prior to TRA GBM. Patients with pre-operative imaging diagnosed with GBM (1 January 2014-31 March 2022) were identified from a neuroscience center.

Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.

Introduction: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema.

Developing consensus in Histopathology: the role of the Delphi method.

The Delphi method is a well-established research tool, used for consensus building across a number of fields. Despite its widespread use, and popularity in many medical specialities, there is a paucity of literature on the use of the Delphi method in Histopathology. This literature review seeks to critique the Delphi methodology and explore its potential applications to histopathology-based clinical and research questions.

Determining the real site of peroneal nerve injury with knee dislocation: Earlierier is easier.

Common peroneal nerve (CPN) injury is a recognised complication of traumatic knee dislocation with a direct association between the degree of ligamentous injury and the degree of CPN injury. It is essential explore and repair these injuries in good time to reduce morbidity. Often exploration only involves the portion of this nerve associated with the joint as it courses around the fibular head.

Can quantifying the extent of 'high grade' features help explain prognostic variability in anaplastic astrocytoma?

Purpose: Both phenotypic and genotypic variations now underpin glioma classification, thus helping to more accurately guide their clinical management. However, WHO Grade III anaplastic astrocytoma (AA) remains an unpredictable, heterogeneous entity; displaying a variable prognosis, clinical course and treatment response. This study aims to examine whether additional tumour characteristics influence either overall survival (OS) or 3-year survival in AA.

Correction to: Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia.

An amendment to this paper has been published and can be accessed via the original article.

DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study.

Background: Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments.

Methods: This population-based study assessed the diagnostic and clinical use of DNA methylation-based profiling in childhood CNS tumours using two large national cohorts in the UK.

Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations.

Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia.

Alzheimer's disease (AD)-related amyloid β-peptide (Aβ) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and undergoes qualitative changes in its composition of modified Aβ species throughout the pathogenesis of AD. It is not clear which of these aspects of Aβ pathology contribute to AD progression and to what extent amyloid positron emission tomography (PET) reflects each of these aspects. To address these questions three cohorts of human autopsy cases (in total n = 271) were neuropathologically and biochemically examined for the topographical distribution of Aβ pathology (plaques and CAA), its quantity and its composition.

Incidence of childhood CNS tumours in Britain and variation in rates by definition of malignant behaviour: population-based study.

Background: Intracranial and intraspinal tumours are the most numerous solid tumours in children. Some recently defined subtypes are relatively frequent in childhood. Many cancer registries routinely ascertain CNS tumours of all behaviours, while others only cover malignant neoplasms.

Estimation of amyloid distribution by [F]flutemetamol PET predicts the neuropathological phase of amyloid β-protein deposition.

The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer's disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging.

How to analyse the spatiotemporal tumour samples needed to investigate cancer evolution: A case study using paired primary and recurrent glioblastoma.

Many traits of cancer progression (e.g., development of metastases or resistance to therapy) are facilitated by tumour evolution: Darwinian selection of subclones with distinct genotypes or phenotypes that enable such progression.

Low-Grade Glioma with Foci of Early Transformation Does Not Necessarily Require Adjuvant Therapy After Radical Surgical Resection.

Background: Low-grade glioma (LGG) is a slow-growing tumor often found in young adults with minimal or no symptoms. As opposed to true low-grade lesions such as dysembryoplastic neuroepithelial tumors, they are associated with continuous growth and inevitable malignant transformation.

Methods: Case series of patients who have had en bloc resection of LGG with foci of anaplasia found embedded within the tumor specimen and not at margins.

Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection.

In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups.

Description and Validation of Histological Patterns and Proposal of a Dynamic Model of Inflammatory Infiltration in Giant-cell Arteritis.

The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.

High-content analysis of tumour cell invasion in three-dimensional spheroid assays.

Targeting infiltrating tumour cells is an attractive way of combating cancer invasion and metastasis. Here we describe a novel and reproducible method for high content analysis of invading cells using multicellular tumour spheroid assays in a high grade glioma model. Live cell imaging of spheroids generated from glioma cell lines, U87 and U251, gave insight into migration dynamics and cell morphology in response to anti-migratory drugs.

[(18)F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: specific detection of advanced phases of amyloid-β pathology.

Background: Amyloid positron emission tomography (PET) has become an important tool to identify amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. Here, we determined the diagnostic value of the amyloid PET tracer [(18)F]flutemetamol in relation to Aβ pathology at autopsy.

Methods: [(18)F]flutemetamol PET was carried out in a cohort of 68 patients included in a [(18)F]flutemetamol amyloid PET imaging end-of-life study (GE067-007).

Atypical teratoid rhabdoid tumour of the spine: report of a case and literature review.

Atypical teratoid rhabdoid tumour (ATRT) is a rare and highly aggressive malignant neoplasm of the central nervous system (CNS), which occurs predominantly in children less than 2 years of age. There are less than 50 cases described in adult. We report a case of primary spinal ATRT in a 65-year-old male who presented to us with cauda equina syndrome.

Carbon monoxide mediates the anti-apoptotic effects of heme oxygenase-1 in medulloblastoma DAOY cells via K+ channel inhibition.

Tumor cell survival and proliferation is attributable in part to suppression of apoptotic pathways, yet the mechanisms by which cancer cells resist apoptosis are not fully understood. Many cancer cells constitutively express heme oxygenase-1 (HO-1), which catabolizes heme to generate biliverdin, Fe(2+), and carbon monoxide (CO). These breakdown products may play a role in the ability of cancer cells to suppress apoptotic signals.

The conjugation of an AQP1-directed immunotoxin in the study of site-directed therapy within the CNS.

Purpose: The water channel, aquaporin (AQP)1, is highly specific to the choroid plexus (CP) epithelium within the brain. It is therefore a potential target through which therapeutic agents could be selectively directed to the CP. Here we describe the conjugation of a monoclonal antibody (mAb), raised against an extra-cellular domain of AQP1, to the A chain of ricin (RCA).