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Future Oncology (London, England) May 2022We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Glioma patients...
We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12 and 24 months. We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n = 68, 52.3%), long-term memory (n = 46, 35.3%) and short-term memory (n = 39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.
Topics: Brain Neoplasms; Cognition; Glioma; Humans; Neuropsychological Tests
PubMed: 35196869
DOI: 10.2217/fon-2021-0963 -
Laboratory Investigation; a Journal of... Jul 2022Comprehensive molecular profiling has dramatically transformed the diagnostic neuropathology of brain tumors. Diffuse gliomas, the most common and deadly brain tumor... (Review)
Review
Comprehensive molecular profiling has dramatically transformed the diagnostic neuropathology of brain tumors. Diffuse gliomas, the most common and deadly brain tumor variants, are now classified by highly recurrent biomarkers instead of histomorphological characteristics. Several of the key molecular alterations driving glioma classification involve epigenetic dysregulation at a fundamental level, implicating fields of biology not previously thought to play major roles glioma pathogenesis. This article will review the major epigenetic alterations underlying malignant gliomas, their likely mechanisms of action, and potential strategies for their therapeutic targeting.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; Epigenesis, Genetic; Glioma; Humans
PubMed: 35152274
DOI: 10.1038/s41374-022-00741-7 -
Neurologia I Neurochirurgia Polska 2022Haemostasis in brain surgery is mandatory to avoid postoperative re-bleeding and a poor outcome. Postoperative intra-cavity haemorrhage is a frequent complication,...
INTRODUCTION
Haemostasis in brain surgery is mandatory to avoid postoperative re-bleeding and a poor outcome. Postoperative intra-cavity haemorrhage is a frequent complication, especially in surgery of malignant gliomas because of the fragility of pathological vessels.
MATERIAL AND METHODS
In this technical note, we describe our 'compression' technique used to achieve haemostasis in adult patients who underwent surgery for supratentorial malignant gliomas (GBM) at our Institute from January 2019 to January 2022. Peri-operative work-up included clinical status, laboratory data and contrast brain CT, performed at 24 hours after surgery, or earlier for patients with neurological worsening.
RESULTS
A total of 82 patients was included in this study, 46 males (57%) and 36 females (43%). A post-operative intra-cavity haemorrhage was documented by postoperative CT-scan in 3/82 patients (3.65%), and the mean surgical time was 3.66 hours. No late bleeding was observed 48 hours after surgery.
CONCLUSIONS
We have documented the good results of our technique to achieve haemostasis in patients operated for malignant glioma (GBM). The technique described in this study seems to be safe and useful to avoid post-operative bleeding in the surgery of cerebral GBM.
Topics: Adult; Male; Female; Humans; Treatment Outcome; Hemorrhage; Glioma; Hemostatic Techniques; Brain Neoplasms
PubMed: 36458803
DOI: 10.5603/PJNNS.a2022.0074 -
Seminars in Cancer Biology Jan 2021Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases... (Review)
Review
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Discovery; Drug Repositioning; Glioma; Humans
PubMed: 31734137
DOI: 10.1016/j.semcancer.2019.10.018 -
Expert Review of Anticancer Therapy Sep 2022The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the... (Review)
Review
INTRODUCTION
The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the heterogenic genetic landscape of glioblastoma strongly influences cell expansion, proliferation, and therapeutic resistance. Identification of immune evasion pathways opens the way to novel immune-based strategies. This review intends to explore the emerging immunotherapies for HGGs. The immunosuppressive mechanisms related to the tumor microenvironment and future perspectives to overcome glioma immunity barriers are also debated.
AREAS COVERED
An extensive literature review was performed on the PubMed/Medline and ClinicalTrials.gov databases. Only highly relevant articles in English and published in the last 20 years were selected. Data about immunotherapies coming from preclinical and clinical trials were summarized.
EXPERT OPINION
The overall level of evidence about the efficacy and safety of immunotherapies for HGGs is noteworthy. Monoclonal antibodies have been approved as second-line treatment, while peptide vaccines, viral gene strategies, and adoptive technologies proved to boost a vivid antitumor immunization. Malignant brain tumor-treating fields are ever-changing in the upcoming years. Constant refinements and development of new routes of drug administration will permit to design of novel immune-based treatment algorithms thus improving the overall survival.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Immunotherapy; Tumor Microenvironment
PubMed: 35924820
DOI: 10.1080/14737140.2022.2110072 -
Pharmacological Reports : PR Apr 2024Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the... (Review)
Review
Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the median survival rate of GBM patients remains low and equals about 14 months. Due to this fact, there are intensive efforts to find drugs that would help combat GBM. Nowadays cannabinoids are becoming more and more important in the field of cancer and not only because of their properties of antiemetic drugs during chemotherapy. These compounds may have a direct cytotoxic effect on cancer cells. Studies indicate GBM has disturbances in the endocannabinoid system-changes in cannabinoid metabolism as well as in the cannabinoid receptor expression. The GBM cells show expression of cannabinoid receptors 1 and 2 (CB1R and CB2R), which mediate various actions of cannabinoids. Through these receptors, cannabinoids inhibit the proliferation and invasion of GBM cells, along with changing their morphology. Cannabinoids also induce an intrinsic pathway of apoptosis in the tumor. Hence the use of cannabinoids in the treatment of GBM may be beneficial to the patients. So far, studies focusing on using cannabinoids in GBM therapy are mainly preclinical and involve cell lines and mice. The results are promising and show cannabinoids inhibit GBM growth. Several clinical studies are also being carried out. The preliminary results show good tolerance of cannabinoids and prolonged survival after administration of these drugs. In this review, we describe the impact of cannabinoids on GBM and glioma cells in vitro and in animal studies. We also provide overview of clinical trials on using cannabinoids in the treatment of GBM.
Topics: Humans; Mice; Animals; Cannabinoids; Glioblastoma; Glioma; Endocannabinoids; Antineoplastic Agents; Brain Neoplasms
PubMed: 38457018
DOI: 10.1007/s43440-024-00580-x -
Cells Jan 2021The Hippo signaling pathway is a highly conserved pathway involved in tissue development and regeneration that controls organ size through the regulation of cell... (Review)
Review
The Hippo signaling pathway is a highly conserved pathway involved in tissue development and regeneration that controls organ size through the regulation of cell proliferation and apoptosis. The core Hippo pathway is composed of a block of kinases, MST1/2 (Mammalian STE20-like protein kinase 1/2) and LATS1/2 (Large tumor suppressor 1/2), which inhibits nuclear translocation of YAP/TAZ (Yes-Associated Protein 1/Transcriptional co-activator with PDZ-binding motif) and its downstream association with the TEAD (TEA domain) family of transcription factors. This pathway was recently shown to be involved in tumorigenesis and metastasis in several cancers such as lung, breast, or colorectal cancers but is still poorly investigated in brain tumors. Gliomas are the most common and the most lethal primary brain tumors representing about 80% of malignant central nervous system neoplasms. Despite intensive clinical protocol, the prognosis for patients remains very poor due to systematic relapse and treatment failure. Growing evidence demonstrating the role of Hippo signaling in cancer biology and the lack of efficient treatments for malignant gliomas support the idea that this pathway could represent a potential target paving the way for alternative therapeutics. Based on recent advances in the Hippo pathway deciphering, the main goal of this review is to highlight the role of this pathway in gliomas by a state-of-the-art synthesis.
Topics: Animals; Brain Neoplasms; Glioma; Hippo Signaling Pathway; Humans; Neoplasm Proteins; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 33477668
DOI: 10.3390/cells10010184 -
Cell Communication and Signaling : CCS Aug 2020Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about... (Review)
Review
Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25 years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100 nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring. Video Abstract.
Topics: Animals; Biomarkers, Tumor; Drug Resistance, Neoplasm; Exosomes; Glioma; Humans; MicroRNAs; Neoplasm Proteins
PubMed: 32746854
DOI: 10.1186/s12964-020-00623-9 -
Trends in Pharmacological Sciences Feb 2020Glioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in... (Review)
Review
Glioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in various cancers, leading to the development of similar therapies that activate the patient's immune system to eliminate glioma. In this review, we introduce the diverse immunotherapeutic approaches available for treating glioma, highlighting the successes and challenges resulting from current clinical trials. Additionally, we emphasize the effect of multiple clinical factors on immunotherapy to help optimize individualized treatment regimens. Finally, we also highlight several novel concepts and technologies that could be used to design new and/or improve existing immunotherapies. Such approaches will delineate a new blueprint for glioma treatment.
Topics: Brain Neoplasms; Glioma; Humans; Immunologic Factors; Immunotherapy
PubMed: 31973881
DOI: 10.1016/j.tips.2019.12.003 -
Advances in Experimental Medicine and... 2020Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous... (Review)
Review
Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol. Cannabinoids elicit a wide range of central and peripheral effects mostly mediated through cannabinoid receptors. There are two types of specific G-protein-coupled receptors cloned so far, called CB1 and CB2, although an existence of additional cannabinoid-binding receptors has been suggested. CB1 and CB2 differ in their predicted amino acid sequence, tissue distribution, physiological role and signaling mechanisms. Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas. Cannabinoids exert anti-proliferative action in tumor cells. Induction of cell death by cannabinoid treatment relies on the generation of a pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial for regulation of cellular proliferation, differentiation or apoptosis. Increased ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma cells. Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment. Advances in translational research on cannabinoid signaling led to clinical investigations on the use of cannabinoids in treatments of glioblastomas.
Topics: Animals; Brain Neoplasms; Cannabinoids; Glioblastoma; Glioma; Humans; Receptors, Cannabinoid; Signal Transduction; Tumor Microenvironment
PubMed: 32034716
DOI: 10.1007/978-3-030-30651-9_11