Preoperative PET imaging and fluorescence-guided surgery of human glioblastoma using dual-labeled antibody targeting ET receptors in a preclinical mouse model: A theranostic approach.

Glioblastoma (GBM) poses significant challenges regarding complete tumor removal due to its heterogeneity and invasiveness, emphasizing the need for effective therapeutic options. In the last two decades, fluorescence-guided surgery (FGS), employing fluorophores such as 5-aminolevulinic acid (5-ALA) to enhance tumor delineation, has gained attraction among neurosurgeons. However, some low-grade tumors do not show any accumulation of the tracers, and the lack of patient stratification represents an important limitation.

Synthesis and Preclinical Fluorescence Imaging of Dually Functionalized Antibody Conjugates Targeting Endothelin Receptor-Positive Tumors.

For the past two decades, the emerging role of the endothelin (ET) axis in cancer has been extensively investigated, and its involvement in several mechanisms described as "hallmarks of cancer" has clearly highlighted its potential as a therapeutic target. Despite the growing interest in finding effective anticancer drugs, no breakthrough treatment has successfully made its way to the market. Recently, our team reported the development of a new immuno-positron emission tomography probe targeting the ET A receptor (ET, one of the ET receptors) that allows the successful detection of ET glioblastoma, paving the way for the elaboration of novel antibody-based strategies.

Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring.

Unlabelled: Glioblastomas (GBM) are heterogeneous tumors with high metabolic plasticity. Their poor prognosis is linked to the presence of glioblastoma stem cells (GSC), which support resistance to therapy, notably to temozolomide (TMZ). Mesenchymal stem cells (MSC) recruitment to GBM contributes to GSC chemoresistance, by mechanisms still poorly understood.

Persistence of FoxJ1 Pax6 Sox2 ependymal cells throughout life in the human spinal cord.

Ependymal cells lining the central canal of the spinal cord play a crucial role in providing a physical barrier and in the circulation of cerebrospinal fluid. These cells express the FOXJ1 and SOX2 transcription factors in mice and are derived from various neural tube populations, including embryonic roof and floor plate cells. They exhibit a dorsal-ventral expression pattern of spinal cord developmental transcription factors (such as MSX1, PAX6, ARX, and FOXA2), resembling an embryonic-like organization.

ImmunoPET imaging-based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model.

Background: The resistance of glioblastoma stem cells (GSCs) to treatment is one of the causes of glioblastoma (GBM) recurrence. Endothelin A receptor (ET) overexpression in GSCs constitutes an attractive biomarker for targeting this cell subpopulation, as illustrated by several clinical trials evaluating the therapeutic efficacy of endothelin receptor antagonists against GBM. In this context, we have designed an immunoPET radioligand combining the chimeric antibody targeting ET, chimeric-Rendomab A63 (xiRA63), with Zr isotope and evaluated the abilities of xiRA63 and its Fab (ThioFab-xiRA63) to detect ET tumors in a mouse model xenografted orthotopically with patient-derived Gli7 GSCs.

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics.

One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of "biomarker signatures" that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.

Glioma invasion along white matter tracts: A dilemma for neurosurgeons.

Invasive growth along white matter (WM) tracts is one of the most prominent clinicopathological features of glioma and is also an important reason for surgical treatment failure in glioma patients. A full understanding of relevant clinical features and mechanisms is of great significance for finding new therapeutic targets and developing new treatment regimens and strategies. Herein, we review the imaging and histological characteristics of glioma patients with WM tracts invasion and summarize the possible molecular mechanism.

SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme.

Glioblastomas (GBM) are high-grade brain tumors, containing cells with distinct phenotypes and tumorigenic potentials, notably aggressive and treatment-resistant multipotent glioblastoma stem cells (GSC). The molecular mechanisms controlling GSC plasticity and growth have only partly been elucidated. Contact with endothelial cells and the Notch1 pathway control GSC proliferation and fate.

Isolation and Culture of Precursor Cells from the Adult Human Spinal Cord.

We demonstrated the presence of neural stem cells and/or progenitor cells in the adult human spinal cord. This chapter provides materials and methods to harvest high-quality samples of thoracolumbar, lumbar, and sacral adult human spinal cord and human dorsal root ganglia isolated from brain-dead patients who had agreed before passing to donate their bodies to science for therapeutic and scientific advances. The methods to culture precursor cells from the adult human spinal cord are also described.

Isolate and Culture Neural Stem Cells from the Mouse Adult Spinal Cord.

Whereas neural stem cells and their niches have been extensively studied in the brain, little is known on these cells, their environment, and their function in the adult spinal cord. Adult spinal cord neural stem cells are located in a complex niche surrounding the central canal, and these cells expressed genes which are specifically expressed in the caudal central nervous system (CNS). In-depth characterization of these cells in vivo and in vitro will provide interesting clues on the possibility to utilize this endogenous cell pool to treat spinal cord damages.

Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing.

Background: Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma, remains after resection and radiotherapy and the tumoral microenvironment become stiffer. GSC invasion is reported as stiffness sensitive and associated with altered N-glycosylation pattern. Glycocalyx thickness modulates integrins mechanosensing, but details remain elusive and glycosylation enzymes involved are unknown.

hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma.

RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation.

Transformation Foci in IDH1-mutated Gliomas Show STAT3 Phosphorylation and Downregulate the Metabolic Enzyme ETNPPL, a Negative Regulator of Glioma Growth.

IDH1-mutated gliomas are slow-growing brain tumours which progress into high-grade gliomas. The early molecular events causing this progression are ill-defined. Previous studies revealed that 20% of these tumours already have transformation foci.

A novel 3D nanofibre scaffold conserves the plasticity of glioblastoma stem cell invasion by regulating galectin-3 and integrin-β1 expression.

Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown.