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Nutrients Jul 2022Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches.... (Review)
Review
Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches. Lipid-soluble vitamins have gained attention in malignant brain tumors owing to their pleiotropic properties and their anti-cancer potential have been reported in a number of human GBM cell lines. The aim of this paper is to systematically review and describe the roles of various biomarkers regulated by lipid-soluble vitamins, such as vitamins A, D, E, and K, in the pathophysiology of GBM. Briefly, research articles published between 2005 and 2021 were systematically searched and selected from five databases (Scopus, PubMed, Ovid MEDLINE, EMBASE via Ovid, and Web of Science) based on the study's inclusion and exclusion criteria. In addition, a number of hand-searched research articles identified from Google Scholar were also included for the analysis. A total of 40 differentially expressed biomarkers were identified from the 19 eligible studies. The results from the analysis suggest that retinoids activate cell differentiation and suppress the biomarkers responsible for stemness in human GBM cells. Vitamin D appears to preferentially modulate several cell cycle biomarkers, while vitamin E derivatives seem to predominantly modulate biomarkers related to apoptosis. However, vitamin K1 did not appear to induce any significant changes to the Raf/MEK/ERK signaling or apoptotic pathways in human GBM cell lines. From the systematic analysis, 12 biomarkers were identified that may be of interest for further studies, as these were modulated by one or two of these lipid-soluble vitamins.
Topics: Adult; Biomarkers; Brain Neoplasms; Glioblastoma; Humans; Lipids; Vitamins
PubMed: 35889829
DOI: 10.3390/nu14142873 -
The Oncologist Feb 2015Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect.... (Review)
Review
Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events.
Topics: Angiogenesis Inhibitors; Bevacizumab; Disease Management; Glioblastoma; Humans; Venous Thromboembolism
PubMed: 25568148
DOI: 10.1634/theoncologist.2014-0330 -
Brain & Spine 2022Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income... (Review)
Review
BACKGROUND
Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.
METHODS
A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.
RESULTS
The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.
DISCUSSION AND CONCLUSION
Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
PubMed: 36248098
DOI: 10.1016/j.bas.2022.100912 -
Child's Nervous System : ChNS :... Sep 2020Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and... (Review)
Review
INTRODUCTION
Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts.
METHODS
This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed.
RESULTS
501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis.
CONCLUSION
OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.
Topics: Astrocytoma; Humans; Neurofibromatosis 1; Optic Nerve Glioma
PubMed: 32556546
DOI: 10.1007/s00381-020-04724-1 -
International Journal of Molecular... Apr 2022The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences... (Review)
Review
The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and "sensing" capabilities. There is currently limited data on the physical forces in GBM-both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.
Topics: Brain Neoplasms; Cell Line, Tumor; Cell Movement; Extracellular Matrix; Glioblastoma; Humans; Mechanical Phenomena; Tumor Microenvironment
PubMed: 35409420
DOI: 10.3390/ijms23074055 -
Cancers Mar 2022Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies... (Review)
Review
THE ISSUE
Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies gliomas as adult-type diffuse gliomas or circumscribed astrocytic gliomas depending on their histology and molecular features. Spinal astrocytic gliomas are very rare, and nowadays no standard of therapy is available. Treatment options are limited: surgery is often not radical, and adjuvant therapies include mostly radiotherapy (RT) or systemic chemotherapy (CHT). There is lack of knowledge about the efficacy and safety of therapies and their multidisciplinary approaches.
THE AIM OF THE REVIEW
A systematic review of the literature from January 2000 to June 2021 was performed, including both clinical trials and observational studies on histological adult primary spinal cord astrocytomas (SCA), with a minimum follow-up of 6 months and reporting the overall survival, progression-free survival or clinical neurological outcome after any therapeutic approach (surgery, RT or CHT). What are the main findings? A total of 1197 citations were identified by the Medline search and additional records; based on our inclusion criteria, 18 studies were included with a total of 285 adult patients. We documented the lack of any clinical trial. What are the conclusions? The available literature data are limited to series/retrospective studies, including heterogeneous patients, i.e., astrocytoma as well as ependymoma or pediatric/adult age, with scanty data on the outcomes of interest. No clinical trials have been run. Due to the rarity of this disease, multicentric clinical trials with molecular investigations are mandatory to better manage such a rare disease.
PubMed: 35267601
DOI: 10.3390/cancers14051292 -
International Journal of Molecular... Feb 2022Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed... (Review)
Review
Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.
Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Signal Transduction
PubMed: 35269752
DOI: 10.3390/ijms23052607 -
Journal of Neurological Surgery Reports Oct 2023Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an...
Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.
PubMed: 37854309
DOI: 10.1055/a-2172-7770 -
Progres En Urologie : Journal de... Feb 2014A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the... (Review)
Review
INTRODUCTION
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.
MATERIAL AND METHOD
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.
RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.
CONCLUSION
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Topics: Humans; Renin-Angiotensin System; Urologic Neoplasms
PubMed: 24485075
DOI: 10.1016/j.purol.2013.09.010 -
The Cochrane Database of Systematic... Apr 2013High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a novel oral chemotherapy drug that penetrates into the brain and purportedly has a low incidence of adverse events.
OBJECTIVES
To assess whether temozolomide has any advantage for treating HGG in either primary or recurrent disease settings.
SEARCH METHODS
The following databases were searched: CENTRAL (Issue 10, 2012), MEDLINE, EMBASE, Science Citation Index, Physician Data Query and the Meta-Register of Controlled Trials in October, 2012. Reference lists of identified studies were searched. The Journal of Neuro-Oncology and Neuro-oncology were handsearched from 1999 to 2012 including conference abstracts. We contacted neuro-oncologists regarding ongoing and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) where the interventions were the use of temozolomide during primary therapy or for recurrent disease. Comparisons included no chemotherapy, non-temozolomide chemotherapy or different dosing schedules of temozolomide. Patients included those of all ages with histologically proven HGG.
DATA COLLECTION AND ANALYSIS
Two review authors undertook the quality assessment and data extraction. Outcome measures included: overall survival (OS); progression-free survival (PFS); quality of life (QoL); and adverse events.
MAIN RESULTS
For primary therapy three RCTs were identified, enrolling a total of 745 patients, that investigated temozolomide in combination with radiotherapy versus radiotherapy alone for glioblastoma multiforme (GBM). Temozolomide increased OS (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.46 to 0.79, P value 0.0003) and increased PFS (HR 0.63, 95% CI 0.43 to 0.92, P value 0.02), when compared with radiotherapy alone, although these benefits only appear to emerge when therapy is given in both concomitant and adjuvant phases of treatment. A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications, fatigue and infections were increased with temozolomide.In recurrent HGG, two RCTs enrolling 672 patients in total found that temozolomide did not increase OS compared to standard chemotherapy (HR 0.9, 95% CI 0.76 to 1.06, P value 0.2) but it did increase PFS in a subgroup analysis of grade IV GBM tumours (HR 0.68, 95% CI 0.51 to 0.90, P value 0.008). Adverse events were similar between arms.In the elderly, 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone. QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide.
AUTHORS' CONCLUSIONS
Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone. It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events. In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression (TTP) and may have benefits on QoL without increasing adverse events but it does not improve overall. In the elderly, temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events.
Topics: Age Factors; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Glioblastoma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Survival Analysis; Temozolomide
PubMed: 23633341
DOI: 10.1002/14651858.CD007415.pub2