Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

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Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v18i2.99 ◽

2020 ◽

Vol 18 (2) ◽

Author(s):

Md Dzali NB ◽

Wan Taib WR ◽

Zahary MN ◽

Abu Bakar NH ◽

Abd Latif AZ ◽

...

Keyword(s):

Brain Tissue ◽

Brain Tumour ◽

Brain Tumours ◽

East Coast ◽

Rna Extraction ◽

Slight Modification ◽

Low Grade ◽

Normal Brain ◽

Sox9 Expression ◽

Sox9 Gene

Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

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Segmentation of Brain Images by Optimizing Clustering of Convolution Based Features

E3S Web of Conferences ◽

10.1051/e3sconf/202122901034 ◽

2021 ◽

Vol 229 ◽

pp. 01034

Author(s):

Vikas Kumar

Keyword(s):

Brain Tumour ◽

Brain Tumours ◽

Normal Brain ◽

Resonance Imaging ◽

Comprehensive Overview ◽

Brain Images ◽

Non Invasive ◽

Tumour Segmentation ◽

Tissue Contrast ◽

Brain Tumour Segmentation

Brain tumour segmentation aims to separate the various types of tumour tissues like active cells, necrotic core, and edema from normal brain tissues of substantia alba (WM), grey matter (GM), and spinal fluid (CSF). Magnetic Resonance Imaging based brain tumour segmentation studies are attracting more and more attention in recent years thanks to non-invasive imaging and good soft tissue contrast of resonance Imaging (MRI) images. With the event of just about two decades, the ingenious approaches applying computer-aided techniques for segmenting brain tumour are getting more and more mature and coming closer to routine clinical applications. the aim of this paper is to supply a comprehensive overview for MRIbased brain tumour segmentation methods. Firstly, a quick introduction to brain tumours and imaging modalities of brain tumours is given in this proposed research, convolution based optimization. These stepwise step refine the segmentation and improve the classification parameter with the assistance of particle swarmoptimization.

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An in vivo multimodal feasibility study in a rat brain tumour model using flexible multinuclear MR and PET systems

10.21203/rs.3.rs-19775/v1 ◽

2020 ◽

Author(s):

Chang-Hoon Choi ◽

Carina Stegmayr ◽

Aliaksandra Shymanskaya ◽

Wieland A. Worthoff ◽

Nuno A da Silva ◽

...

Keyword(s):

Brain Tumour ◽

Small Animal ◽

Optimal Combination ◽

Small Animal Pet ◽

Molecular Profile ◽

Genetic Profile ◽

Normal Brain ◽

Valuable Insight ◽

Wide Range

Abstract Background : In addition to the structural information afforded by 1 H MRI, the use of X-nuclei, such as sodium-23 ( 23 Na) or phosphorus-31 ( 31 P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models.Methods : In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET). This enabled in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET.Results : High-quality in vivo images and spectra including high-resolution 1 H imaging, 23 Na-weighted imaging, detection of 31 P metabolites and 18 F-FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a normal brain. These parameters have been shown to be useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy.Conclusions : The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.

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Metabolic Plasticity of Astrocytes and Aging of the Brain

International Journal of Molecular Sciences ◽

10.3390/ijms20040941 ◽

2019 ◽

Vol 20 (4) ◽

pp. 941 ◽

Cited By ~ 11

Author(s):

Mitsuhiro Morita ◽

Hiroko Ikeshima-Kataoka ◽

Marko Kreft ◽

Nina Vardjan ◽

Robert Zorec ◽

...

Keyword(s):

Systemic Circulation ◽

Brain Parenchyma ◽

Acid Oxidation ◽

Normal Brain ◽

Atp Production ◽

Metabolic Plasticity ◽

Neuronal Synapses ◽

Age Related ◽

Pathologic Processes ◽

The Brain

As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions. In astrocytes, glycolysis and glycogenesis are regulated by noradrenaline and insulin, respectively, while mitochondrial ATP production and fatty acid oxidation are influenced by the thyroid hormone. These regulations are essential for maintaining normal brain activities, and impairments of these processes may lead to neurodegeneration and cognitive decline. Metabolic plasticity is also associated with (re)activation of astrocytes, a process associated with pathologic events. It is likely that the recently described neurodegenerative and neuroprotective subpopulations of reactive astrocytes metabolize distinct energy substrates, and that this preference is supposed to explain some of their impacts on pathologic processes. Importantly, physiologic and pathologic properties of astrocytic metabolic plasticity bear translational potential in defining new potential diagnostic biomarkers and novel therapeutic targets to mitigate neurodegeneration and age-related brain dysfunctions.

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CMET-14. BRAIN METASTASES: A NEW PATHOPHYSIOLOGY, A NEW TREATMENT PARADIGM, AND, PERHAPS, A NEW PROGNOSIS

Neuro-Oncology ◽

10.1093/neuonc/noz175.215 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi54-vi54

Author(s):

Richard Dowd ◽

Tao Ouyang ◽

Krishnamoorthy Thamburaj ◽

Dawit Aregawi ◽

Howard Safran ◽

...

Keyword(s):

Brain Metastases ◽

Substantial Reduction ◽

Blood Stream ◽

Brain Parenchyma ◽

Neoplastic Meningitis ◽

Normal Brain ◽

Malignant Cells ◽

Therapeutic Implications ◽

Treatment Paradigm ◽

Pre Treatment

Abstract INTRODUCTION Brain metastases are widely held to reach the CNS through the blood stream. We provide evidence that the initial site of most CNS metastases is the CSF, with subsequent invasion of brain parenchyma. We also model the therapeutic implications of this novel hypothesis. METHODS Two neuro-radiologists independently assessed whether brain metastases were contiguous with CSF spaces in 200 consecutive patients using pre-treatment MRI. CSF was examined for malignant cells in 66 newly diagnosed, previously untreated patients. We contoured normal brain MRIs of 3 patients to calculate the percentage of brain within 5 mm of a CSF space. We queried an international neoplastic meningitis database to document response of brain metastases to intra-CSF chemotherapy. RESULTS Mean age was 64.2. One hundred patients were male; 143 had lung cancer, 15 melanoma, 12 gastrointestinal, 11 breast, 9 renal, 7 bladder. Mean number of metastases was 4.63. Eighty-five percent of metastases touched a CSF space. In 67% of patients, all metastases touched a CSF space. Neither histology, number or size of metastases, nor patient age predicted contiguity with CSF spaces. In our consecutive subset of patients, 44% (10/23) with one, 46% (5/11) with two, 63% (5/8) with three, and 71% (17/24) with >3 metastases had malignant cells in the CSF (R2=0.93, p=0.037). Five of 7 patients with both brain and CSF metastases receiving only IT chemotherapy experienced a substantial reduction in the size of at least some metastases. Up to 75% of the brain parenchyma lies within 5 mm of CSF spaces. CONCLUSIONS Our data suggest that brain metastases may access the CNS through the CSF rather than the bloodstream. IT chemotherapy may treat brain metastases. We suggest that the CSF should be monitored in all patients with, or at risk for, brain metastases. True cures may require treatment of the CSF space.

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Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma

Journal of Experimental Medicine ◽

10.1084/jem.20111102 ◽

2011 ◽

Vol 208 (13) ◽

pp. 2657-2673 ◽

Cited By ~ 35

Author(s):

Ming Li ◽

Akitake Mukasa ◽

Maria del-Mar Inda ◽

Jianhua Zhang ◽

Lynda Chin ◽

...

Keyword(s):

Cell Lines ◽

Cell Invasion ◽

Glioma Cell ◽

Binding Protein ◽

Brain Parenchyma ◽

Normal Brain ◽

Matrix Metalloproteinase 1 ◽

Egfr Expression ◽

Egfr Activation ◽

Guanylate Binding Protein

Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.

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