Chondroitin Sulphate Proteoglycans in the Tumour Microenvironment.

Proteoglycans are macromolecules that are essential for the development of cells, human diseases and malignancies. In particular, chondroitin sulphate proteoglycans (CSPGs) accumulate in tumour stroma and play a key role in tumour growth and invasion by driving multiple oncogenic pathways in tumour cells and promoting crucial interactions in the tumour microenvironment (TME). These pathways involve receptor tyrosine kinase (RTK) signalling via the mitogen-activated protein kinase (MAPK) cascade and integrin signalling via the activation of focal adhesion kinase (FAK), which sustains the activation of extracellular signal-regulated kinases 1/2 (ERK1/2).

Chondroitin Sulphate Proteoglycan 4 (NG2/CSPG4) Localization in Low- and High-Grade Gliomas.

Background: Neuron glial antigen 2 or chondroitin sulphate proteoglycan 4 (NG2/CSPG4) is expressed by immature precursors/progenitor cells and is possibly involved in malignant cell transformation. The aim of this study was to investigate its role on the progression and survival of sixty-one adult gliomas and nine glioblastoma (GB)-derived cell lines.

Methods: NG2/CSPG4 protein expression was assessed by immunohistochemistry and immunofluorescence.

Regulation of R1 Plasmid Transfer by H-NS, ArcA, TraJ, and DNA Sequence Elements.

In conjugative elements such as integrating conjugative elements (ICEs) or conjugative plasmids (CPs) transcription of DNA transfer genes is a prerequisite for cells to become transfer competent, i.e., capable of delivering plasmid DNA via bacterial conjugation into new host bacteria.

Validation of Thiosemicarbazone Compounds as P-Glycoprotein Inhibitors in Human Primary Brain-Blood Barrier and Glioblastoma Stem Cells.

P-glycoprotein (Pgp) is highly expressed on blood-brain barrier (BBB) and glioblastoma (GB) cells, particularly on cancer stem cells (SC). Pgp recognizes a broad spectrum of substrates, limiting the therapeutic efficacy of several chemotherapeutic drugs in eradicating GB SC. Finding effective and safe inhibitors of Pgp that improve drug delivery across the BBB and target GB SC is open to investigation.

SEL1L plays a major role in human malignant gliomas.

Suppressor of Lin-12-like (C. elegans) (SEL1L) participates in the endoplasmic reticulum-associated protein degradation pathway, malignant transformation and stem cell biology. We explored the role of SEL1L in 110 adult gliomas, of different molecular subtype and grade, in relation to cell proliferation, stemness, glioma-associated microglia/macrophages (GAMs), prognostic markers and clinical outcome.

Glioblastoma: Microenvironment and Niche Concept.

The niche concept was originally developed to describe the location of normal neural stem cells (NSCs) in the subependymal layer of the sub-ventricular zone. In this paper, its significance has been extended to the location of tumor stem cells in glioblastoma (GB) to discuss the relationship between GB stem cells (GSCs) and endothelial cells (ECs). Their interaction is basically conceived as responsible for tumor growth, invasion and recurrence.

Carbonic Anhydrase XII Inhibitors Overcome P-Glycoprotein-Mediated Resistance to Temozolomide in Glioblastoma.

The role of carbonic anhydrase XII (CAXII) in the chemoresistance of glioblastoma is unexplored. We found CAXII and P-glycoprotein (Pgp) coexpressed in neurospheres derived from 3 of 3 patients with different genetic backgrounds and low response to temozolomide (time to recurrence: 6-9 months). CAXII was necessary for the Pgp efflux of temozolomide and second-line chemotherapeutic drugs, determining chemoresistance in neurospheres.

Correction: SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.

[This corrects the article DOI: 10.18632/oncotarget.3611.

The Significance of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Human Gliomas.

Neuron glial antigen 2 (NG2) is a chondroitin sulphate proteoglycan 4 (CSPG4) that occurs in developing and adult central nervous systems (CNSs) as a marker of oligodendrocyte precursor cells (OPCs) together with platelet-derived growth factor receptor α (PDGFRα). It behaves variably in different pathological conditions, and is possibly involved in the origin and progression of human gliomas. In the latter, NG2/CSPG4 induces cell proliferation and migration, is highly expressed in pericytes, and plays a role in neoangiogenesis.

Microglia immunophenotyping in gliomas.

Microglia, once assimilated to peripheral macrophages, in gliomas has long been discussed and currently it is hypothesized to play a pro-tumor role in tumor progression. Uncertain between M1 and M2 polarization, it exchanges signals with glioma cells to create an immunosuppressive microenvironment and stimulates cell proliferation and migration. Four antibodies are currently used for microglia/macrophage identification in tissues that exhibit different cell forms and cell localization.

Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies.

Aim: To develop an innovative delivery system for temozolomide (TMZ) in solid lipid nanoparticles (SLN), which has been preliminarily investigated for the treatment of melanoma.

Materials And Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma.

Comparison among conventional and advanced MRI, F-FDG PET/CT, phenotype and genotype in glioblastoma.

Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique.

The neuropathological basis to the functional role of microglia/macrophages in gliomas.

The paper wants to be a tracking shot of the main recent acquisitions on the function and significance of microglia/macrophages in gliomas. The observations have been principally carried out on in vitro cultures and on tumor transplants in animals. Contrary to what is deduced from microglia in non-neoplastic pathologic conditions of central nervous system (CNS), most conclusions indicate that microglia acts favoring tumor proliferation through an immunosuppression induced by glioma cells.

Chemotherapeutic Drugs: DNA Damage and Repair in Glioblastoma.

Despite improvements in therapeutic strategies, glioblastoma (GB) remains one of the most lethal cancers. The presence of the blood-brain barrier, the infiltrative nature of the tumor and several resistance mechanisms account for the failure of current treatments. Distinct DNA repair pathways can neutralize the cytotoxicity of chemo- and radio-therapeutic agents, driving resistance and tumor relapse.

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic.

Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment.

Aim: Methotrexate-loaded biocompatible nanoparticles were tested for preliminary efficacy in glioma treatment.

Materials & Methods: Behenic acid nanoparticles, prepared by the coacervation method, were loaded with the ester prodrug didodecylmethotrexate, which was previously tested in vitro against glioblastoma human primary cultures. Nanoparticle conjugation with an ApoE mimicking chimera peptide was performed to obtain active targeting to the brain.

Diagnostic revision of 206 adult gliomas (including 40 oligoastrocytomas) based on ATRX, IDH1/2 and 1p/19q status.

The diagnosis of 206 low and high grade adult gliomas, including 40 oligoastrocytomas, was revised based on the immunohistochemical reactivity for the ATRX protein, IDH1/2 mutation status and 1p/19q chromosomal status. All oligodendrogliomas kept the initial diagnosis. Astrocytomas did not change diagnosis in 30 of 36 cases (83.

Myeloperoxidase-responsive materials for infection detection based on immobilized aminomethoxyphenol.

There is a strong need for simple and fast diagnostic tools for the detection of wound infection. Immune system-derived enzymes like myeloperoxidase are efficient biomarkers for wound infection that emerge in the early stage infection process. In this study, 5-amino-2-methoxyphenol was functionalized with alkoxysilane to allow visual detection of MPO on carrier materials, for example, in test strips.

Mesenchymal/radioresistant traits in granular astrocytomas: evidence from a combined clinical and molecular approach.

Aims: Granular-cell astrocytomas (GCAs) are morphologically characterized by a prominent component of granular periodic acid-Schiff-positive cells, and show increased aggressiveness as compared with 'ordinary' astrocytomas. The aim of this study was to investigate, in a small series of three GCAs, the expression of mesenchymal/radioresistance-associated biomarkers [such as chitinase-3-like protein 1 (YKL-40), hepatocyte growth factor receptor (c-Met), and caveolin 1 (Cav1)] that could contribute to the poor outcome associated with this glioma subgroup.

Methods And Results: Our results show that GCAs, according to the new molecular glioma classifications, consistently show a prognostically negative molecular trait (IDH1wt-ATRX noloss-1p/19q nocodeletion).

WNT/β-catenin Signaling Pathway and Downstream Modulators in Low- and High-grade Glioma.

Background: Aberrant activation of the canonical Wingless-type MMTV integration site family (WNT)/β-catenin signaling pathway is critical for gliomas.

Materials And Methods: In 74 gliomas of different histological grade and in 24 glioblastoma cell lines, protein expression of WNT member 3a (WNT3a), β-catenin and transcription factor 4 (TCF4) was investigated by immunohistochemistry, western blotting, immunofluorescence and immunocytochemistry. In tumors and cell lines, WNT3A expression was assessed at the mRNA level by quantitative real-time polymerase chain reaction.

The Microenvironment in Gliomas: Phenotypic Expressions.

The microenvironment of malignant gliomas is described according to its definition in the literature. Beside tumor cells, a series of stromal cells (microglia/macrophages, pericytes, fibroblasts, endothelial cells, normal and reactive astrocytes) represents the cell component, whereas a complex network of molecular signaling represents the functional component. Its most evident expressions are perivascular and perinecrotic niches that are believed to be the site of tumor stem cells or progenitors in the tumor.

Fast Blue RR-Siloxane Derivatized Materials Indicate Wound Infection Due to a Deep Blue Color Development.

There is a strong need for simple and fast methods for wound infection determination. Myeloperoxidase, an immune system-derived enzyme was found to be a suitable biomarker for wound infection. Hence, alkoxysilane-derivatized Fast Blue RR was immobilized via simple hydrolytic polymerization.

Neuroscience, the microscope and the truth: personal philosophical considerations by a professor emeritus of neuropathology and neurology.

The article starts from the conception that the world is introduced in our mind though linguistic categories and that between us and the world there is always the language. This implies that to denominate still means to know. The visual pathway is described from the retina to the occipital cortex with the related phenomena of the recognition of the external world, through the Gestalt psychology, the reciprocal influence of sign/receptor, the mental images or patterns, the cognition, the conscience and memory.