scholarly journals Mechanisms of Invasion in Glioblastoma: Extracellular Matrix, Ca2+ Signaling, and Glutamate

2021 ◽  
Vol 15 ◽  
Author(s):  
Jae-Seon So ◽  
Hyeono Kim ◽  
Kyung-Seok Han
Keyword(s):  
Extracellular Matrix ◽  
Brain Tumor ◽  
Primary Brain Tumor ◽  
Therapeutic Interventions ◽  
Signaling Cascades ◽  
Migration And Invasion ◽  
Cellular Mechanisms ◽  
Brain Tumor Cells ◽  
Complete Surgical Resection ◽  
The Brain

Glioblastoma (GBM) is the most common and malignant form of primary brain tumor with a median survival time of 14–16 months in GBM patients. Surgical treatment with chemotherapy and radiotherapy may help increase survival by removing GBM from the brain. However, complete surgical resection to eliminate GBM is almost impossible due to its high invasiveness. When GBM cells migrate to the brain, they interact with various cells, including astrocytes, neurons, endothelial cells, and the extracellular matrix (ECM). They can also make their cell body shrink to infiltrate into narrow spaces in the brain; thereby, they can invade regions of the brain and escape from surgery. Brain tumor cells create an appropriate microenvironment for migration and invasion by modifying and degrading the ECM. During those processes, the Ca2+ signaling pathway and other signaling cascades mediated by various ion channels contribute mainly to gene expression, motility, and invasion of GBM cells. Furthermore, GBM cells release glutamate, affecting migration via activation of ionotropic glutamate receptors in an autocrine manner. This review focuses on the cellular mechanisms of glioblastoma invasion and motility related to ECM, Ca2+ signaling, and glutamate. Finally, we discuss possible therapeutic interventions to inhibit invasion by GBM cells.

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

Extracellular matrix in plasticity and epileptogenesis

2008 ◽  
Vol 4 (3) ◽  
pp. 235-247 ◽  
Author(s):  
Alexander Dityatev ◽  
Tommaso Fellin
Keyword(s):  
Extracellular Matrix ◽  
Developmental Plasticity ◽  
Mossy Fibers ◽  
Long Term Potentiation ◽  
Therapeutic Interventions ◽  
Neural Cells ◽  
Dependent Manner ◽  
Extracellular Proteases ◽  
Mature Brain ◽  
The Brain

Extracellular matrix (ECM) in the brain is composed of molecules synthesized and secreted by neurons and glial cells in a cell-type-specific and activity-dependent manner. During development, ECM plays crucial roles in proliferation, migration and differentiation of neural cells. In the mature brain, ECM undergoes a slow turnover and supports multiple physiological processes, while restraining structural plasticity. In the first part of this review, we discuss the contribution of ECM molecules to different forms of plasticity, including developmental plasticity in the cortex, long-term potentiation and depression in the hippocampus, homeostatic scaling of synaptic transmission and metaplasticity. In the second part, we focus on pathological changes associated with epileptogenic mutations in ECM-related molecules or caused by seizure-induced remodeling of ECM. The available data suggest that ECM components regulating physiological plasticity are also engaged in different aspects of epileptogenesis, such as dysregulation of excitatory and inhibitory neurotransmission, sprouting of mossy fibers, granule cell dispersion and gliosis. At the end, we discuss combinatorial approaches that might be used to counteract seizure-induced dysregulation of both ECM molecules and extracellular proteases. By restraining ECM modification and preserving the status quo in the brain, these treatments might prove to be valid therapeutic interventions to antagonize the progression of epileptogenesis.

scholarly journals Novel delivery methods bypassing the blood-brain and blood-tumor barriers

2015 ◽  
Vol 38 (3) ◽  
pp. E10 ◽  
Author(s):  
Benjamin K. Hendricks ◽  
Aaron A. Cohen-Gadol ◽  
James C. Miller
Keyword(s):  
Primary Brain Tumor ◽  
Pathological Process ◽  
Therapeutic Interventions ◽  
Delivery Methods ◽  
Ongoing Research ◽  
Functional Capabilities ◽  
Blood Brain ◽  
Natural Protection ◽  
The Brain ◽  
Brain Homeostasis

Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM. In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.

scholarly journals Opportunities and challenges of glioma organoids

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiangdong Xu ◽  
Lingfei Li ◽  
Linting Luo ◽  
Lingling Shu ◽  
Xiaoli Si ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Animal Models ◽  
3D Structure ◽  
Primary Brain Tumor ◽  
Surgical Removal ◽  
Human Tissues ◽  
Cell Models ◽  
Cell Dynamics ◽  
Research Platform ◽  
The Brain

AbstractGlioma is the most common primary brain tumor and its prognosis is poor. Despite surgical removal, glioma is still prone to recurrence because it grows rapidly in the brain, is resistant to chemotherapy, and is highly aggressive. Therefore, there is an urgent need for a platform to study the cell dynamics of gliomas in order to discover the characteristics of the disease and develop more effective treatments. Although 2D cell models and animal models in previous studies have provided great help for our research, they also have many defects. Recently, scientific researchers have constructed a 3D structure called Organoids, which is similar to the structure of human tissues and organs. Organoids can perfectly compensate for the shortcomings of previous glioma models and are currently the most suitable research platform for glioma research. Therefore, we review the three methods currently used to establish glioma organoids. And introduced how they play a role in the diagnosis and treatment of glioma. Finally, we also summarized the current bottlenecks and difficulties encountered by glioma organoids, and the current efforts to solve these difficulties.

scholarly journals Dense Hierarchical CNN – A Unified Approach for Brain Tumor Segmentation

2021 ◽  
Vol 35 (3) ◽  
pp. 223-233
Author(s):  
Roohi Sille ◽  
Tanupriya Choudhury ◽  
Piyush Chauhan ◽  
Durgansh Sharma
Keyword(s):  
Brain Tumor ◽  
Signal To Noise Ratio ◽  
Imaging Techniques ◽  
Tumor Segmentation ◽  
Neoplastic Tissue ◽  
Brain Tumor Segmentation ◽  
Brain Tumor Cells ◽  
Segmentation Algorithms ◽  
Heterogeneous Nature ◽  
The Brain

Brain tumor segmentation is an essential and challenging task because of the heterogeneous nature of neoplastic tissue in spatial and imaging techniques. Manual segmentation of the tumor in MRI images is prone to error and time-consuming tasks. An efficient segmentation mechanism is vital to the accurate classification and segmentation of tumorous cells. This study presents an efficient hierarchical clustering-based dense CNN approach for accurately classifying and segmenting the brain tumor cells in MRI images. The research focuses on improving the efficiency of the segmentation algorithms by considering the qualitative measures such as the dice score coefficient using quantitative parameters such as mean square error and peak signal to noise ratio. The experimental analysis states the efficacy and prominence of the proposed technique compared to other models are tabulated within the paper.

scholarly journals Acanthosis nigricans and the sign of leser-trelat associated with primary brain tumor: Case report

2008 ◽  
Vol 16 (3-4) ◽  
pp. 81-83
Author(s):  
Slobodan Stojanovic ◽  
Pavle Jeremic ◽  
Mirjana Poljacki
Keyword(s):  
Brain Tumor ◽  
Acanthosis Nigricans ◽  
Neck Region ◽  
Primary Brain Tumor ◽  
Skin Tumors ◽  
Low Grade ◽  
Seborrheic Keratosis ◽  
Skin Changes ◽  
Clinical Changes ◽  
The Brain

The authors present a case of a female patient a 26-year old pensioner from Zmajevo, who developed skin changes in the neck region, armpits and groins, as well as in submammal folds during the 10 years period. The changes include dark-brown hyper?pigmentation associated with sudden eruption of a large number of benign skin tumors and dark-brown seborrheic keratosis on trunk and extremities. In 1998, after magnetic resonance imaging, primary brain tumor of astrocytoma type with low grade of malignity was discovered in thalamus region. The patient developed the above-mentioned skin changes since then. According to neurosurgical findings, the brain tumor is inoperable, so skin changes are persistent and stationary. Clinical changes correspond to paraneoplastic form of acanthosis nigricans. Numerous skin tumors histopathologically match seborrheic keratosis and reveal the clinical features of the sign of Leser-Trelat. It is interesting that in the same patient there are both, obligatory and optional, paraneoplastic dermatoses associated with malignant brain tumor.

scholarly journals The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

2020 ◽  
Vol 21 (19) ◽  
pp. 7358
Author(s):  
Fiona A. Desland ◽  
Adília Hormigo
Keyword(s):  
T Cells ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Modulation ◽  
Primary Brain Tumor ◽  
Cellular Heterogeneity ◽  
Checkpoint Molecule ◽  
Engineered T Cells ◽  
Immunosuppressive Tumor Microenvironment ◽  
The Brain

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.

scholarly journals ANALYSIS OF TUMOR DETECTION USING UNETS AND VGG16 WEIGHTS

2021 ◽  
Vol 10 (4) ◽  
pp. 3191-3195
Author(s):  
V Kakulapati
Keyword(s):  
Brain Tumor ◽  
Brain Mri ◽  
Diagnostic Testing ◽  
Medical Science ◽  
Tumor Detection ◽  
Therapeutic Interventions ◽  
Computer Algorithms ◽  
Tumor Identification ◽  
Time Image ◽  
The Brain

Tumor detection from Brain MRI images Abstract: Detecting tumors in the human brain has become the most challenging medical science issue. Recognition of tumors in MRIs is vital as it offers the aberrant relevant data for therapeutic interventions. MRI includes details on malignant tissue. An abnormal tissue growing and multiplying in the brain is a brain tumor. Physical examination is the standard approach for brain tumor identification, which takes much time and is not accurate every time. So, automated brain tumor identification methods are establishing to save time. Image segmentation utilizes to detect the brain's abnormal portion, which gives the tumor's location. This work uses the UNETS with VGG16 weights model to see and segment tumors from the rest of the brain tissue. The accurate detection of the tumors helps reduce the delay between diagnostic testing and therapy. Therefore, there is a significant demand for computer algorithms to be precise, speedy, time-efficient, and dependable. The technology described relates to detecting and analyzing brain cancers automatically via U-Net and the VGG16 CNN.

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