scholarly journals Fusion Genes Altered in Adult Malignant Gliomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Gan You ◽  
Xing Fan ◽  
Huimin Hu ◽  
Tao Jiang ◽  
Clark C. Chen
Keyword(s):  
Genetic Background ◽  
Molecular Genetic ◽  
Malignant Gliomas ◽  
Therapeutic Targets ◽  
High Grade ◽  
Gene Fusions ◽  
Fusion Genes ◽  
High Grade Gliomas ◽  
The Many

Malignant gliomas are highly heterogeneous brain tumors in molecular genetic background. Despite the many recent advances in the understanding of this disease, patients with adult high-grade gliomas retain a notoriously poor prognosis. Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets to date. Understanding the gene fusions and how they regulate oncogenesis and malignant progression will contribute to explore new approaches for personalized treatment. By now, studies on gene fusions in gliomas remain limited. However, some current clinical trials targeting fusion genes have presented exciting preliminary findings. The aim of this review is to summarize all the reported fusion genes in high-grade gliomas so far, discuss the characterization of some of the most popular gene fusions occurring in malignant gliomas, as well as their function in tumorigenesis, and the underlying clinical implication as therapeutic targets.

scholarly journals Sonodynamic Therapy for the Treatment of Intracranial Gliomas

2021 ◽  
Vol 10 (5) ◽  
pp. 1101
Author(s):  
Antonio D’Ammando ◽  
Luca Raspagliesi ◽  
Matteo Gionso ◽  
Andrea Franzini ◽  
Edoardo Porto ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
High Grade ◽  
Sonodynamic Therapy ◽  
Treatment Protocols ◽  
Ultrasound Waves ◽  
High Grade Gliomas ◽  
Preclinical And Clinical Studies

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas

2003 ◽  
Vol 21 (12) ◽  
pp. 2299-2304 ◽  
Author(s):  
Howard A. Fine ◽  
Patrick Y. Wen ◽  
Elizabeth A. Maher ◽  
Elene Viscosi ◽  
Tracy Batchelor ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Malignant Gliomas ◽  
Cytotoxic Agents ◽  
Clinical Activity ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Antiangiogenic Agent ◽  
Histologic Diagnosis ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas

Purpose: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. Patients and Methods: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. Results: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. Conclusion: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.

TH-E-ValB-06: Quantitative Characterization of Tumor Vascular Dysfunction in High-Grade Gliomas Prior to and During Radiotherapy

2006 ◽  
Vol 33 (6Part23) ◽  
pp. 2290-2290
Author(s):  
V Nagesh ◽  
T Chenevert ◽  
L Junck ◽  
C Tsien ◽  
T Lawrence ◽  
...  
Keyword(s):  
Vascular Dysfunction ◽  
High Grade ◽  
Quantitative Characterization ◽  
High Grade Gliomas

scholarly journals Applications of Radiomics and Radiogenomics in High-Grade Gliomas in the Era of Precision Medicine

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5921
Author(s):  
Anahita Fathi Kazerooni ◽  
Stephen J. Bagley ◽  
Hamed Akbari ◽  
Sanjay Saxena ◽  
Sina Bagheri ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Extent Of Resection ◽  
Target Area ◽  
High Grade ◽  
Future Directions ◽  
Mri Scans ◽  
High Grade Gliomas ◽  
Changes Over Time

Machine learning (ML) integrated with medical imaging has introduced new perspectives in precision diagnostics of high-grade gliomas, through radiomics and radiogenomics. This has raised hopes for characterizing noninvasive and in vivo biomarkers for prediction of patient survival, tumor recurrence, and genomics and therefore encouraging treatments tailored to individualized needs. Characterization of tumor infiltration based on pre-operative multi-parametric magnetic resonance imaging (MP-MRI) scans may allow prediction of the loci of future tumor recurrence and thereby aid in planning the course of treatment for the patients, such as optimizing the extent of resection and the dose and target area of radiation. Imaging signatures of tumor genomics can help in identifying the patients who benefit from certain targeted therapies. Specifying molecular properties of gliomas and prediction of their changes over time and with treatment would allow optimization of treatment. In this article, we provide neuro-oncology, neuropathology, and computational perspectives on the promise of radiomics and radiogenomics for allowing personalized treatments of patients with gliomas and discuss the challenges and limitations of these methods in multi-institutional clinical trials and suggestions to mitigate the issues and the future directions.

scholarly journals Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas

2016 ◽  
Vol 11 (1) ◽  
Author(s):  
Lina Mörén ◽  
Carl Wibom ◽  
Per Bergström ◽  
Mikael Johansson ◽  
Henrik Antti ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
High Grade ◽  
High Grade Gliomas

Current strategies for the treatment of malignant gliomas – experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw

2020 ◽  
Vol 92 (4) ◽  
pp. 1-5
Author(s):  
Grzegorz Turek ◽  
Tomasz Pasterski ◽  
Krzysztof Bankiewicz ◽  
Sebastian Dzierzęcki ◽  
Mirosław Ząbek
Keyword(s):  
Brain Tumors ◽  
San Francisco ◽  
Malignant Gliomas ◽  
High Grade ◽  
Current Standard ◽  
Convection Enhanced Delivery ◽  
Surgical Methods ◽  
High Grade Gliomas ◽  
Standard Medical Treatment ◽  
Intraoperative Electrical Stimulation

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. Material and methods: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management – from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. Results: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. Discussion: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

scholarly journals ONCOLYTIC VIRUSES IN HIGH-GRADE GLIOMAS TREATMENT

2015 ◽  
Vol 6 (2) ◽  
pp. 46-59 ◽  
Author(s):  
V P Baklaushev ◽  
S A Goryainov ◽  
А А Potapov ◽  
G V Pavlova ◽  
V P Chehonin
Keyword(s):  
Clinical Trials ◽  
Clinical Guidelines ◽  
Laboratory Tests ◽  
State Of The Art ◽  
Malignant Gliomas ◽  
Point Of View ◽  
Oncolytic Viruses ◽  
High Grade ◽  
Preclinical Trials ◽  
High Grade Gliomas

The review examines the state of the art of diagnosis and therapy of high-grade gliomas both by currently existing clinical guidelines, and from the point of view of the most promising approaches of currently undergoing laboratory tests and the first clinical trials. One of the most promising approach for the treatment of malignant gliomas is the nonpathogenic oncolytic viruses (OV) application. The data of preclinical trials of OV and the first preliminary results of clinical trials are discussed.

scholarly journals Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 71597-71617 ◽  
Author(s):  
Aurélia Nguyen ◽  
François Marie Moussallieh ◽  
Alan Mackay ◽  
A. Ercument Cicek ◽  
Andres Coca ◽  
...  
Keyword(s):  
Metabolic Responses ◽  
High Grade ◽  
High Grade Gliomas

scholarly journals Analysis of genetic aberrations in pediatric high-grade gliomas

2020 ◽  
Vol 7 (3) ◽  
pp. 37-47
Author(s):  
M. A. Zaytseva ◽  
A. P. Shekhtman ◽  
L. I. Papusha ◽  
E. F. Valiakhmetova ◽  
L. A. Yasko ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Clinical Care ◽  
Molecular Genetic ◽  
Driver Mutations ◽  
High Grade ◽  
Missense Mutations ◽  
Genetic Aberrations ◽  
Genomic Landscape ◽  
Wide Range ◽  
High Grade Gliomas

Background. High-grade gliomas are characterized by a wide range of genetic abnormalities. The heterogeneous genomic landscape of pediatric high-grade gliomas allows identifying distinct subgroups of the disease in children and young adults. Most importantly, these subgroups differ by clinical course and prognosis, as well as treatment response to standard therapy.Objective: to assess the profile of molecular genetic markers of high-grade gliomas in children.Materials and methods. In the current study, we examine the frequency of H3F3A, Hist1H3B, BRAF, IDH1 / 2 mutations, the copy number alterations of CDKN2A / 2B genes and the expression of ETV6‑NTRK3 fusion gene in a cohort of 53 pediatric high-grade gliomas.Results. Driver mutations and CDKN2A / 2B deletions were observed in 24 (45 %) and 15 (28 %) of 53 tumors, respectively. Overall, the studied high-grade gliomas harbored 41 genetic aberrations including 24 (58.5 %) somatic missense mutations, 1 (2.4 %) genetic variant of unknown clinical significance, 1 (2.4 %) oncogenic fusion gene and 15 (36.6 %) deletions of the tumor suppressor genes.Conclusion. These findings point to the importance of molecular profiling of tumors for the optimal clinical care and development of new approaches to treatment aimed at molecular targets for personalized anticancer therapies.

scholarly journals Ion Channels as Therapeutic Targets in High Grade Gliomas

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3068
Author(s):  
Michaela Griffin ◽  
Raheela Khan ◽  
Surajit Basu ◽  
Stuart Smith
Keyword(s):  
Ion Channels ◽  
Treatment Options ◽  
Cell Cycle Control ◽  
Therapeutic Targets ◽  
High Grade ◽  
Neoplastic Progression ◽  
Invasion And Migration ◽  
Average Survival ◽  
High Grade Gliomas ◽  
And Migration

Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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