scholarly journals Ion Channels in Glioblastoma

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Remco J. Molenaar
Keyword(s):  
Brain Tumor ◽  
Sodium Chloride ◽  
Ion Channels ◽  
Calcium Channels ◽  
Surgical Resection ◽  
Median Survival ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Potassium Sodium ◽  
Dismal Prognosis

Glioblastoma is the most common primary brain tumor with the most dismal prognosis. It is characterized by extensive invasion, migration, and angiogenesis. Median survival is only 15 months due to this behavior, rendering focal surgical resection ineffective and adequate radiotherapy impossible. At this moment, several ion channels have been implicated in glioblastoma proliferation, migration, and invasion. This paper summarizes studies on potassium, sodium, chloride, and calcium channels of glioblastoma. It provides an up-to-date overview of the literature that could ultimately lead to new therapeutic targets.

scholarly journals A Review of Newly Diagnosed Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Bryan Oronsky ◽  
Tony R. Reid ◽  
Arnold Oronsky ◽  
Navjot Sandhu ◽  
Susan J. Knox
Keyword(s):  
Brain Tumor ◽  
Surgical Resection ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Genetic Characteristics ◽  
Dismal Prognosis ◽  
Newly Diagnosed Glioblastoma ◽  
Temozolomide Chemotherapy

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.

scholarly journals GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoting Yu ◽  
Jing Jin ◽  
Yanwen Zheng ◽  
Hua Zhu ◽  
Hui Xu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Rna Interference ◽  
Tumor Growth ◽  
Survival Time ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Novel Target

AbstractGuanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

scholarly journals Impact of surgical resection of butterfly glioblastoma on survival: a meta-analysis based on comparative studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafał Chojak ◽  
Marta Koźba-Gosztyła ◽  
Katarzyna Słychan ◽  
Daniel Gajos ◽  
Marek Kotas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Tumor ◽  
Relative Risk ◽  
Corpus Callosum ◽  
Surgical Resection ◽  
Treatment Option ◽  
Meta Analysis ◽  
Random Effects Model ◽  
Benefit Ratio ◽  
Dismal Prognosis

AbstractButterfly glioblastoma (bGBM) is a rare brain tumor that invades both hemispheres by crossing the corpus callosum. bGBM is associated with a dismal prognosis with a median survival time of a few months. Surgical resection is a rare treatment option due to the unfavorable location and assumed poor risk-to-benefit ratio. Therefore, a biopsy-alone approach is considered the main treatment option. This meta-analysis aimed to systematically evaluate whether resection of bGBM is associated with improved overall survival compared with biopsy alone. We searched three databases to find studies that compare resection with biopsy in 6-, 12- and 18-months overall survival in patients with bGBM. We calculated the pooled relative risk (RR) of mortality using a random-effects model. Five studies with 194 patients were included in the meta-analysis. Mortality was decreased for resection compared with biopsy at 6-months (RR 0.63 [95% CI 0.44–0.91]). No significant differences in overall survival were found at 12 (RR 0.76 [95% CI 0.50–1.14]) and 18-months (RR 0.84 [95% CI 0.56–1.26]). Surgical resection of bGBM is associated with an improved 6-months overall survival compared with biopsy alone. We have not found strong evidence supporting the superiority of resection over biopsy alone in overall survival at 12 and 18-months.

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.

CSIG-03. GBP5 DRIVES MALIGNANCY OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi33-vi33
Author(s):  
Ming Li ◽  
Clark Chen
Keyword(s):  
Brain Tumor ◽  
Rna Interference ◽  
Tumor Growth ◽  
Survival Time ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Novel Target

Abstract Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

scholarly journals Challenges in Immunotherapy Presented by the Glioblastoma Multiforme Microenvironment

2011 ◽  
Vol 2011 ◽  
pp. 1-20 ◽  
Author(s):  
Christopher Jackson ◽  
Jacob Ruzevick ◽  
Jillian Phallen ◽  
Zineb Belcaid ◽  
Michael Lim
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Tumor Microenvironment ◽  
Median Survival ◽  
Immune Surveillance ◽  
Cell Types ◽  
Primary Brain Tumor ◽  
Cellular Level ◽  
Significant Challenge ◽  
Multiple Signaling

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite intensive treatment, the prognosis for patients with GBM remains grim with a median survival of only 14.6 months. Immunotherapy has emerged as a promising approach for treating many cancers and affords the advantages of cellular-level specificity and the potential to generate durable immune surveillance. The complexity of the tumor microenvironment poses a significant challenge to the development of immunotherapy for GBM, as multiple signaling pathways, cytokines, and cell types are intricately coordinated to generate an immunosuppressive milieu. The development of new immunotherapy approaches frequently uncovers new mechanisms of tumor-mediated immunosuppression. In this review, we discuss many of the current approaches to immunotherapy and focus on the challenges presented by the tumor microenvironment.

Deglucohellebrin: A Potent Agent for Glioblastoma Treatment

2020 ◽  
Vol 20 (1) ◽  
pp. 103-110
Author(s):  
Evrysthenis Vartholomatos ◽  
George A. Alexiou ◽  
Georgios S. Markopoulos ◽  
Diamanto Lazari ◽  
Olga Tsiftsoglou ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Primary Brain Tumor ◽  
Behavioral Alterations ◽  
Endemic Plant ◽  
M Cell ◽  
Apoptotic Pathway ◽  
Cycle Arrest ◽  
Dismal Prognosis ◽  
Mitochondrial Membrane Depolarization ◽  
Induced Changes

Background: Glioblastoma is the most common primary brain tumor in adults with a dismal prognosis. To date, several anticancer agents have been isolated from plants. Helleborus odorus subsp. Cyclophyllus is an endemic plant of the Balcan flora. Herewith, we investigated for the first time, the anti-glioma effect of deglucohellebrin (DGH) extracted from the roots of Helleborus. Methods: We investigated the effect of DGH in U251MG, T98G and U87G glioblastoma cell lines. We selected the T98G cells because of their inherent temozolomide resistance. Results: The IC50 value of reduced viability for DGH was 7x10-5M in U251MG cells, 5x10-5M for the T98G cells and 4x10-5M in U87G cells during 72h treatment. DGH induced G2/M cell cycle arrest, caspace-8 activation and significant mitochondrial membrane depolarization, suggesting the activation of the intrinsic, mitochondrial- dependent apoptotic pathway. DGH and temozolomide induced changes in CDs’ expression in U251MG and T98G cells. In zebrafish, DGH did not induce toxicity or behavioral alterations. Conclusion: The present study is the first to determine the anti-glioma activity of DGH. DGH may be a potent agent for glioblastoma treatment and further studies are needed.

scholarly journals NCMP-13. LEPTOMENINGEAL DISEASE FOLLOWING RESECTION OF INTRAVENTRICULAR MELANOMA METASTASIS DIAGNOSED THROUGH CIRCULATING TUMOR CELLS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii125-ii125
Author(s):  
Christopher Wang ◽  
Melissa Limia ◽  
Peter Forsyth ◽  
James Liu
Keyword(s):  
Early Intervention ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Surgical Resection ◽  
Tumor Resection ◽  
Leptomeningeal Disease ◽  
Melanoma Metastasis ◽  
Tumor Seeding ◽  
Csf Analysis ◽  
Dismal Prognosis

Abstract Leptomeningeal disease in the setting of malignant melanoma metastatic to the brain provides a dismal prognosis. The relationship between intraventricular metastatic tumor seeding following surgical resection and development of leptomeningeal disease (LMD) is not completely clear, although there appears to be correlation. While the mechanisms that drive the development of LMD is not well understood, monitoring of cerebrospinal fluid (CSF) for circulating tumor cells (CTCs) in high risk patients may allow for early intervention for LMD prior to radiographical diagnosis. This report describes a patient with metastatic melanoma who developed ventricular trapping from an intraventricular melanoma metastasis. The patient underwent endoscopic assisted resection of the tumor. Due to concern for leptomeningeal seeding given the location of the tumor and use of surgical resection, CSF analysis was performed. CTC count was increased shortly after surgical resection along with cytology that was suspicious for malignancy. Due to the increase in CTCs, the patient was treated for LMD with whole brain radiation therapy and intrathecal pembrolizumab. Subsequent CSF analysis revealed clearing of malignant cells in the CSF. The patient developed symptoms consistent with LMD approximately 9 months after the surgery and died 21 months after resection of his brain metastasis. This case illustrates a rare occurrence of an intraventricular melanoma metastasis, and the use of CTC presence within the CSF to diagnose LMD for early intervention. This emphasizes that the risk of developing LMD must be considered with intraventricular metastasis or ventricular exposure during tumor resection, and that CTCs may be an effective factor to monitor for early development of disease with possible prolonged survival benefit.

Prognostic histopathologic features of canine glial tumors

2021 ◽  
pp. 030098582110257
Author(s):  
Joshua L. Merickel ◽  
G. Elizabeth Pluhar ◽  
Aaron Rendahl ◽  
M. Gerard O’Sullivan
Keyword(s):  
Brain Tumor ◽  
Median Survival ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Translational Model ◽  
Poor Survival ◽  
Whole Brain ◽  
Tumor Types ◽  
Tumor Biopsies ◽  
Prognostic Data

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( P < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( P < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.

scholarly journals Prospects of immune checkpoint blockade and vaccine-based immunotherapy for glioblastoma

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stefanie Tietze ◽  
Susanne Michen ◽  
Gabriele Schackert ◽  
Achim Temme
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Primary Brain Tumor ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Therapeutic Vaccines ◽  
Dismal Prognosis ◽  
Tumor Parenchyma ◽  
Immunosuppressive Microenvironment

Abstract Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor endowed with a dismal prognosis. Nowadays, immunotherapy in a particular immune checkpoint blockade and therapeutic vaccines are being extensively pursued. Yet, several characteristics of GBM may impact such immunotherapeutic approaches. This includes tumor heterogeneity, the relatively low mutational load of primary GBM, insufficient delivery of antibodies to tumor parenchyma and the unique immunosuppressive microenvironment of GBM. Moreover, standard treatment of GBM, comprising temozolomide chemotherapy, radiotherapy and in most instances the application of glucocorticoids for management of brain edema, results in a further increased immunosuppression. This review will provide a brief introduction to the principles of vaccine-based immunotherapy and give an overview of the current clinical studies, which employed immune checkpoint inhibitors, oncolytic viruses-based vaccination, cell-based and peptide-based vaccines. Recent experiences as well as the latest developments are reviewed. Overcoming obstacles, which limit the induction and long-term immune response against GBM when using vaccination approaches, are necessary for the implementation of effective immunotherapy of GBM.

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