Publications by authors named "Weller M"

Background: EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being among its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signaling compared with wildtype EGFR.

Methods: To better understand the oncogenic role of EGFRvIII, we leveraged 4 large datasets into 1 large glioblastoma transcriptome dataset (n = 741) alongside 81 whole-genome samples from 2 datasets.

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Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers.

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The trafficking of illegal drugs by criminal networks at borders, harbors, or airports is an increasing issue for public health as these routes ensure the main supply of illegal drugs. The prevention of drug smuggling, including the installation of scanners and other analytical devices to detect small traces of drugs within a reasonable time frame, remains a challenge. The presented immunosensor is based on a monolithic affinity column with a large excess of immobilized hapten, which traps fluorescently labeled antibodies as long as the analyte cocaine is absent.

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Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach.

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Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank.

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Objective: The My Baby's Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (the MBM intervention).

Design: Stepped-wedge cluster-randomised controlled trial.

Setting: Twenty-seven maternity hospitals in Australia and New Zealand.

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Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma.

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We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%.

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Purpose: There is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting.

Methods: We retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2-4) at the University Hospital Zurich, Switzerland, in the years 2005-2019.

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Recent therapeutic advances involving the use of systemic targeted treatments and immunotherapeutic agents in patients with advanced cancers have translated into improved survival rates. Despite the emergence of such promising pharmacological therapies and extended survival, the frequency of metastases in the central nervous system has steadily increased. Effective medical and surgical therapies are available for many patients with brain metastases and need to be incorporated into multi-disciplinary care protocols.

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The allergenic and inflammatory potential of proteins can be enhanced by chemical modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms and kinetics of such modifications, however, have not yet been fully resolved. We investigated the oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O), nitrogen dioxide (NO), and peroxynitrite (ONOO).

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Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy.

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Background: The incidence of spinal cord gliomas, particularly in adults is low, and the role of chemotherapy has remained unclear.

Methods: We performed a multicenter, retrospective study of 21 patients diagnosed with spinal cord glioma who received chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by magnetic resonance imaging.

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Background: The Response Assessment in Neuro-Oncology Patient-Reported Outcome (RANO-PRO) working group aims to provide guidance on the use of PROs in brain tumor patients. PRO measures should be of high quality, both in terms of relevance and other measurement properties. This systematic review aimed to identify PRO measures that have been used in brain tumor studies to date.

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Background And Purpose: Delirium is a common severe complication of stroke. We aimed to determine the cost-of-illness and risk factors of poststroke delirium (PSD).

Methods: This prospective single-center study included n=567 patients with acute stroke from a hospital-wide delirium cohort study and the Swiss Stroke Registry in 2014.

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Article Synopsis
  • * The majority of non-study patients received high dose methotrexate (HDMTX), but their overall survival was significantly lower (6 months) compared to study patients who also received HDMTX (20-21 months).
  • * Key factors for better prognosis in non-study patients included younger age, receiving HDMTX, and a positive early response in MRI results; these findings suggest potential for long-term control of the disease even in those not qualified for trials
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This review article outlines the current development of emerging treatment strategies for primary central nervous system lymphoma, a rare brain tumor with, thus far, limited therapeutic options. Small molecule targeted tyrosine kinase inhibitors, immunomodulatory agents, and immune checkpoint inhibitors will be discussed. The mechanisms of action, results of completed clinical studies, ongoing clinical trials, and future perspectives are summarized.

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Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma.

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Article Synopsis
  • This document aims to update the 2000 AAN guidelines on using anticonvulsants in patients with newly diagnosed brain tumors.
  • A systematic review of relevant studies showed that most evidence was of lower quality (class II and III) with a few high-quality studies (class I).
  • Key recommendations include not prescribing antiepileptic drugs for seizure prevention in patients without seizures and limited evidence for using specific drugs to improve survival or reduce seizure risk during surgery.
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Background: The Safer Baby Bundle (SBB) eLearning is an online education module that addresses practice gaps in stillbirth prevention in Australia. It provides healthcare professionals with evidence-based resources for: smoking cessation; fetal growth restriction; decreased fetal movements; maternal safe going-to-sleep position; and timing of birth for women with risk factors for stillbirth.

Aims: To determine whether participants' reported knowledge and confidence in providing care designed to reduce stillbirth changed following completion of the module.

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Article Synopsis
  • Computational tools are increasingly used to identify biological targets of natural products with anticancer effects, particularly the natural product piperlongumine (PL), which interacts with the hTRPV2 channel.
  • Cryo-electron microscopy revealed how PL binds to an allosteric pocket of the rat TRPV2 channel, showcasing a novel anticancer mechanism against glioblastoma (GBM), where the hTRPV2 channel is overexpressed.
  • Research demonstrated that downregulating hTRPV2 decreases sensitivity to PL, and treating GBM in mouse models with PL formulated in a scaffold significantly reduced tumor growth and improved survival, suggesting a new approach for cancer treatment.
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Background: For patients with recurrent glioblastoma (rGBM), there are few options following treatment failure with radiotherapy plus temozolomide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 antibody blocking PD-L1.

Methods: In this phase I, open-label expansion cohort (NCT02517398), patients with rGBM that progressed after radiotherapy plus temozolomide received bintrafusp alfa 1200 mg Q2W until disease progression, unacceptable toxicity, or trial withdrawal.

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