- Keywords
- GLIOMA/diagnosis *,
- MeSH
- Glioma diagnosis MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
PURPOSE: Evaluate the effectiveness of treatment of patients with optic pathway glioma. MATERIALS AND METHODS: Comparison of literature research on neurofibromatosis and optic pathway glioma with a cohort of pediatric patients treated at the Childrens Ophthalmology Clinic of the University Hospital in Brno from January 2013 until June 2018. DISCUSSION: The main challenge of this and other retrospective studies is variable intervals between ophthalmologic examinations. In some pediatric patients it is also difficult to objectively assess visual functions. The main risk factors are age at the time of treatment and tumor localization. Tumor progression itself does not always correlate with worse visual acuity outcomes, and it remains to be evaluated whether some patients would be better off without treatment. As of now, there are no clinical biomarkers able to predict impending visual acuity loss. CONCLUSION: The cohort outcome agrees with literature. Chemotherapy remains a treatment of choice and its most likely outcome is visual acuity stabilization. In order to properly evaluate the treatments effectiveness, better collaboration between medical specialists and regular standardized ophthalmology examinations are required.
- Keywords
- chemotherapy, children, neurofibromatosis, optic pathway glioma, treatment,
- MeSH
- Child MeSH
- Optic Nerve Glioma therapy MeSH
- Humans MeSH
- Neurofibromatosis 1 therapy MeSH
- Vision Disorders MeSH
- Retrospective Studies MeSH
- Visual Acuity MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Major advances in the genomics and epigenomics of diffuse gliomas and glioblastoma to date have not been translated into effective therapy, necessitating pursuit of alternative treatment approaches for these therapeutically challenging tumors. Current knowledge of microtubules in cancer and the development of new microtubule-based treatment strategies for high-grade gliomas are the topic in this review article. Discussed are cellular, molecular, and pharmacologic aspects of the microtubule cytoskeleton underlying mitosis and interactions with other cellular partners involved in cell cycle progression, directional cell migration, and tumor invasion. Special focus is placed on (1) the aberrant overexpression of βIII-tubulin, a survival factor associated with hypoxic tumor microenvironment and dynamic instability of microtubules; (2) the ectopic overexpression of γ-tubulin, which in addition to its conventional role as a microtubule-nucleating protein has recently emerged as a transcription factor interacting with oncogenes and kinases; (3) the microtubule-severing ATPase spastin and its emerging role in cell motility of glioblastoma cells; and (4) the modulating role of posttranslational modifications of tubulin in the context of interaction of microtubules with motor proteins. Specific antineoplastic strategies discussed include downregulation of targeted molecules aimed at achieving a sensitization effect on currently used mainstay therapies. The potential role of new classes of tubulin-binding agents and ATPase inhibitors is also examined. Understanding the cellular and molecular mechanisms underpinning the distinct behaviors of microtubules in glioma tumorigenesis and drug resistance is key to the discovery of novel molecular targets that will fundamentally change the prognostic outlook of patients with diffuse high-grade gliomas.
- MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Glioma drug therapy genetics metabolism MeSH
- Carcinogenesis drug effects genetics metabolism MeSH
- Humans MeSH
- Microtubules drug effects genetics metabolism MeSH
- Neural Networks, Computer MeSH
- Gene Expression Regulation, Neoplastic drug effects genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Antineoplastic Agents MeSH
Glioma is the most pernicious cancer of the nervous system, with histological grade influencing the survival of patients. Despite many studies on the multimodal treatment approach, survival time remains brief. In this study, a novel two-stage ensemble of an ensemble-type machine learning-based predictive framework for glioma detection and its histograde classification is proposed. In the proposed framework, five characteristics belonging to 135 subjects were considered: human telomerase reverse transcriptase (hTERT), chitinase-like protein (YKL-40), interleukin 6 (IL-6), tissue inhibitor of metalloproteinase-1 (TIMP-1) and neutrophil/lymphocyte ratio (NLR). These characteristics were examined using distinctive ensemble-based machine learning classifiers and combination strategies to develop a computer-aided diagnostic system for the non-invasive prediction of glioma cases and their grade. In the first stage, the analysis was conducted to classify glioma cases and control subjects. Machine learning approaches were applied in the second stage to classify the recognised glioma cases into three grades, from grade II, which has a good prognosis, to grade IV, which is also known as glioblastoma. All experiments were evaluated with a five-fold cross-validation method, and the classification results were analysed using different statistical parameters. The proposed approach obtained a high value of accuracy and other statistical parameters compared with other state-of-the-art machine learning classifiers. Therefore, the proposed framework can be utilised for designing other intervention strategies for the prediction of glioma cases and their grades.
- Keywords
- Biomarkers, Data analysis, Ensemble learning, Glioma, Machine learning,
- MeSH
- Glioma * diagnosis MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Neoplasms * diagnosis MeSH
- Machine Learning * MeSH
- Neoplasm Grading MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Malignant gliomas are among the most severe types of cancer, and the most common primary brain tumors. Treatment options are limited and the prognosis is poor. WNT-5A, a member of the WNT family of lipoglycoproteins, plays a role in oncogenesis and tumor progression in various cancers, whereas the role of WNT-5A in glioma remains obscure. Based on the role of WNT-5A as an oncogene, its potential to regulate microglia cells and the glioma-promoting capacities of microglia cells, we hypothesize that WNT-5A has a role in regulation of immune functions in glioma. We investigated WNT-5A expression by in silico analysis of the cancer genome atlas (TCGA) transcript profiling of human glioblastoma samples and immunohistochemistry experiments of human glioma tissue microarrays (TMA). Our results reveal higher WNT-5A protein levels and mRNA expression in a subgroup of gliomas (WNT-5A(high)) compared to non-malignant control brain tissue. Furthermore, we show a significant correlation between WNT-5A in the tumor and presence of major histocompatibility complex Class II-positive microglia/monocytes. Our data pinpoint a positive correlation between WNT-5A and a proinflammatory signature in glioma. We identify increased presence of microglia/monocytes as an important aspect in the inflammatory transformation suggesting a novel role for WNT-5A in human glioma.
- Keywords
- Glioma, Major histocompatibility complex II, Microglia, Tumor microenvironment, WNT-5A,
- MeSH
- Tissue Array Analysis MeSH
- Glioma metabolism pathology MeSH
- Humans MeSH
- Microglia metabolism pathology MeSH
- Monocytes metabolism pathology MeSH
- Wnt-5a Protein MeSH
- Wnt Proteins biosynthesis genetics metabolism MeSH
- Proto-Oncogene Proteins biosynthesis genetics metabolism MeSH
- Computational Biology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Wnt-5a Protein MeSH
- Wnt Proteins MeSH
- Proto-Oncogene Proteins MeSH
- WNT5A protein, human MeSH Browser
Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.
- Keywords
- GliMR 2.0, brain, contrasts, glioma, level of clinical validation, preoperative,
- MeSH
- Glioma * diagnostic imaging surgery pathology MeSH
- Contrast Media MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Neoplasms * diagnostic imaging surgery pathology MeSH
- Preoperative Period MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Contrast Media MeSH
BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.
- MeSH
- Diffuse Intrinsic Pontine Glioma genetics diagnosis blood MeSH
- Child MeSH
- Epigenesis, Genetic MeSH
- Glioma genetics diagnosis blood pathology diagnostic imaging MeSH
- Histones * genetics metabolism blood MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation MeSH
- Biomarkers, Tumor blood MeSH
- Brain Stem Neoplasms genetics diagnosis blood diagnostic imaging pathology metabolism MeSH
- Child, Preschool MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Histones * MeSH
- Biomarkers, Tumor MeSH
Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.
- Keywords
- GliMR 2.0, brain, contrasts, glioma, level of clinical validation, preoperative,
- MeSH
- Diffusion Magnetic Resonance Imaging MeSH
- Glioma * diagnostic imaging surgery pathology MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Magnetic Resonance Imaging methods MeSH
- Brain Neoplasms * diagnostic imaging surgery pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Research Support, N.I.H., Extramural MeSH
Changes in the size and dry mass of glioma C-6 intact cells in culture were investigated for 35-50 min at 5 min intervals by means of vital cytointerferometry. Rhythmic variations in the size, dry mass and protein concentration were thereby revealed in glioma cells. These variations fall into the category of circahoralian ones. While considerable variations in the cell area and dry mass were observed, changes in protein concentration were less pronounced. Addition of dibutyryl cylic AMP (db-cAMP), in a concentration of 10(-3) mol/l to the cultivation medium, produced no effect on the rhythm of the above parameters in glioma C-6 cells.
Single potassium channels in the membrane of human malignant glioma cells U-118MG were studied using the technique of patch clamp in cell-attached and inside-out configurations. Three types of potassium channels were found which differed from each other under conditions close to physiological in their conductance and gating characteristics. The lowest-conductance channel (20 pS near the reversal potential) showed a mild outward rectification up to 45 pS at positive voltages and spontaneous modes of high and low activity. At extreme values of potentials its activity was generally low. The intermediate conductance channel had an S-shaped I-V curve, giving a conductance of 63 pS at reversal, and a low and voltage independent opening probability. The high-conductance (215 pS) channel was found to be activated by both membrane potential and Ca2+ ions and blocked by internal sodium at high voltages. The current-voltage curves of all three channel types displayed saturation.
- MeSH
- Potassium pharmacokinetics MeSH
- Potassium Channels physiology MeSH
- Electrophysiology MeSH
- Ion Channel Gating drug effects MeSH
- Glioma metabolism MeSH
- Humans MeSH
- Membrane Potentials MeSH
- Tumor Cells, Cultured MeSH
- Sodium pharmacology MeSH
- Calcium pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Potassium MeSH
- Potassium Channels MeSH
- Sodium MeSH
- Calcium MeSH
