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Acta Biomaterialia Feb 2021The treatment for glioblastoma multiforme (GBM) has not changed for more than 20 years while the prognosis for the patients is still poor and most of them survive less... (Review)
Review
The treatment for glioblastoma multiforme (GBM) has not changed for more than 20 years while the prognosis for the patients is still poor and most of them survive less than 1 year after diagnosis. The standard of care for GBM is comprised of surgical resection followed by radiotherapy and oral chemotherapy with temozolomide. The placement of carmustine wafers in the brain after tumour removal is added in cases of recurrent glioma. Significant research is underway to improve the GBM therapy outcome and patient quality of life. Biomaterials are in the front line of the research focus for new treatment options. Specially, biocompatible polymers have been proposed in hydrogel-based formulations aiming at injectable and localized therapies. These formulations can comprise many different pharmacological agents such as chemotherapeutic drugs, nanoparticles, cells, nucleic acids, and diagnostic agents. In this manuscript, we review the most recent formulations developed and tested both in vitro and in vivo using different types of hydrogels. Firstly, we describe three common types of thermo-responsive polymers addressing the advantages and drawbacks of their formulations. Then, we focus on formulations specifically developed for GBM treatment.
Topics: Brain Neoplasms; Carmustine; Glioblastoma; Humans; Neoplasm Recurrence, Local; Polymers; Quality of Life
PubMed: 33227487
DOI: 10.1016/j.actbio.2020.11.030 -
International Journal of Molecular... Apr 2019Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system, with poor survival in both treated and untreated patients. Recent... (Review)
Review
Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system, with poor survival in both treated and untreated patients. Recent studies began to explain the molecular pathway, comprising the dynamic structural and mechanical changes involved in GBM. In this context, some studies showed that the human glioblastoma cells release high levels of glutamate, which regulates the proliferation and survival of neuronal progenitor cells. Considering that cancer cells possess properties in common with neural progenitor cells, it is likely that the functions of glutamate receptors may affect the growth of cancer cells and, therefore, open the road to new and more targeted therapies.
Topics: Animals; Biomechanical Phenomena; Cell Movement; Central Nervous System Neoplasms; Glioblastoma; Glutamic Acid; Humans; Ion Channels; Neoplasm Invasiveness; Receptors, Glutamate; Receptors, Metabotropic Glutamate; Signal Transduction
PubMed: 30978987
DOI: 10.3390/ijms20071796 -
Cancer Biology & Therapy Apr 2013Glioblastoma Multiforme (GBM) is the most aggressive brain tumor characterized by intratumoral heterogeneity at cytopathological, genomic and transcriptional levels.... (Review)
Review
Glioblastoma Multiforme (GBM) is the most aggressive brain tumor characterized by intratumoral heterogeneity at cytopathological, genomic and transcriptional levels. Despite the efforts to develop new therapeutic strategies the median survival of GBM patients is 12-14 months. Results from large-scale gene expression profile studies confirmed that the genetic alterations in GBM affect pathways controlling cell cycle progression, cellular proliferation and survival and invasion ability, which may explain the difficulty to treat GBM patients. One of the signaling pathways that contribute to the aggressive behavior of glioma cells is the protein kinase C (PKC) pathway. PKC is a family of serine/threonine-specific protein kinases organized into three groups according the activating domains. Due to the variability of actions controlled by PKC isoforms, its contribution to the development of GBM is poorly understood. This review intends to highlight the contribution of PKC isoforms to proliferation, survival and invasive ability of glioma cells.
Topics: Animals; Brain Neoplasms; Glioblastoma; Humans; Protein Kinase C; Signal Transduction
PubMed: 23358475
DOI: 10.4161/cbt.23615 -
Frontiers in Bioscience (Landmark... Mar 2022Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM...
BACKGROUND
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy.
METHODS
Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry.
RESULTS
Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4.
CONCLUSIONS
Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.
Topics: Adult; Brain Neoplasms; Cell Line; Glioblastoma; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Vascular Endothelial Growth Factor A
PubMed: 35345329
DOI: 10.31083/j.fbl2703097 -
International Journal of Molecular... Jun 2021Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to... (Review)
Review
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).
Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Drug Delivery Systems; Drug Resistance, Neoplasm; Glioblastoma; Humans; Immune Evasion
PubMed: 34203727
DOI: 10.3390/ijms22126385 -
TheScientificWorldJournal Apr 2011Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem... (Review)
Review
Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.
Topics: Animals; Biomarkers; Epigenesis, Genetic; Glioblastoma; Humans; Immunosuppression Therapy; Mice; Neoplastic Stem Cells; Signal Transduction
PubMed: 21516289
DOI: 10.1100/tsw.2011.42 -
Journal of Immunology Research 2017Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard... (Review)
Review
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints.
Topics: Adult; B7-H1 Antigen; Brain Neoplasms; CTLA-4 Antigen; Cancer Vaccines; Clinical Trials as Topic; Glioblastoma; Humans; Immunotherapy; Precision Medicine
PubMed: 28299344
DOI: 10.1155/2017/3597613 -
BMC Genomics Dec 2023Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with a poor prognosis. The C-C motif chemokine ligand 2 (CCL2) has shown abnormal...
BACKGROUND
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with a poor prognosis. The C-C motif chemokine ligand 2 (CCL2) has shown abnormal expression associated with progression of multiple malignancies, however, its role in predicting the prognosis and immunotherapy response of GBM remains poorly understood.
RESULTS
CCL2 was highly expressed in GBM as analyzed by integrating CGGA, GEPIA and UALCAN online platforms, and further verified by histologic examinations, qRT-PCR analysis, and independent GEO datasets. CCL2 could serve as an independent prognostic factor for both the poor overall survival and progression-free survival of GBM patients based on TCGA data, univariate and multivariate cox analyses. Functional enrichment analysis revealed that CCL2 mainly participated in the regulation of chemokine signaling pathway and inflammatory response. Further, CCL2 expression was positively correlated with CD4 T cells, macrophages, neutrophils and myeloid dendritic cells infiltrating GBM as calculated by the TIMER2.0 algorithm. Importantly, the tumor immune dysfunction and exclusion (TIDE) algorithm showed that in CCL2-high GBM group, the expression of CD274, CTLA4, HAVCR2 and other immune checkpoints were significantly increased, and the immune checkpoint blockade (ICB) therapy was accordingly more responsive.
CONCLUSIONS
CCL2 can be used as a predictor of prognosis as well as immunotherapy response in GBM, offering potential clinical implications.
Topics: Humans; Glioblastoma; Ligands; Brain Neoplasms; Prognosis; Chemokines; Immunotherapy; Chemokine CCL2
PubMed: 38057698
DOI: 10.1186/s12864-023-09674-x -
Journal of the Egyptian National Cancer... Mar 2013This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). (Review)
Review
INTRODUCTION
This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM).
SUBJECTS AND METHOD
This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM.
RESULTS
There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival.
CONCLUSION
The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival.
Topics: Adult; Aged; Brain Neoplasms; Combined Modality Therapy; Disease-Free Survival; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Prognosis; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 23499203
DOI: 10.1016/j.jnci.2012.11.001 -
Seminars in Cancer Biology Nov 2022Despite an aggressive standard of care involving radiation therapy, temozolomide-based chemotherapy, and surgical resection, glioblastoma multiforme (GBM) continues to... (Review)
Review
Despite an aggressive standard of care involving radiation therapy, temozolomide-based chemotherapy, and surgical resection, glioblastoma multiforme (GBM) continues to exhibit very high recurrence and mortality rates partly due to the highly plastic and heterogenous nature of the tumor. In recent years, activation of the immune system has emerged as a promising strategy in cancer therapies. However, despite recent successes in other fields, immunotherapeutic approaches continue to encounter challenges in GBM. In this review, we first discuss immunotherapies targeting the most well-studied immune checkpoint proteins, CTLA-4 and PD-1, followed by discussions on therapies targeting immune-stimulatory molecules and secreted metabolic enzymes. Finally, we address the major challenges with immunotherapy in GBM and the potential for combination and neoadjuvant immunotherapies to tip the scales in the fight against glioblastoma.
Topics: Humans; Glioblastoma; Immunotherapy; Temozolomide; Biological Transport; Neoadjuvant Therapy
PubMed: 35150865
DOI: 10.1016/j.semcancer.2022.02.012