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Journal of Controlled Release :... Jul 2023Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system and has a poor prognosis. GBM cells are highly sensitive to ferroptosis and heat,...
Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system and has a poor prognosis. GBM cells are highly sensitive to ferroptosis and heat, suggesting thermotherapy-ferroptosis as a new strategy for GBM treatment. With its biocompatibility and photothermal conversion efficiency, graphdiyne (GDY) has become a high-profile nanomaterial. Here, the ferroptosis inducer FIN56 was employed to construct GDY-FIN56-RAP (GFR) polymer self-assembled nanoplatforms against GBM. GDY could effectively load FIN56 and FIN56 released from GFR in a pH-dependent manner. The GFR nanoplatforms possessed the advantages of penetrating the BBB and acidic environment-induced in situ FIN56 release. Moreover, GFR nanoplatforms induced GBM cell ferroptosis by inhibiting GPX4 expression, and 808 nm irradiation reinforced GFR-mediated ferroptosis by elevating the temperature and promoting FIN56 release from GFR. In addition, the GFR nanoplatforms were inclined to locate in tumor tissue, inhibit GBM growth, and prolong lifespan by inducing GPX4-mediated ferroptosis in an orthotopic xenograft mouse model of GBM; meanwhile, 808 nm irradiation further improved these GFR-mediated effects. Hence, GFR may be a potential nanomedicine for cancer therapy, and GFR combined with photothermal therapy may be a promising strategy against GBM.
Topics: Humans; Animals; Mice; Glioblastoma; Photothermal Therapy; Ferroptosis; Graphite; Cell Line, Tumor
PubMed: 37244298
DOI: 10.1016/j.jconrel.2023.05.035 -
Neuro-oncology Aug 2023People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of...
BACKGROUND
People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.
METHODS
Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally.
RESULTS
Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18-68 years) and performance status of 80% (30%-100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2-267 months] across all ages, and 38.5 [18-109] months in individuals with grade 1-2 gliomas.
CONCLUSIONS
Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
Topics: Female; Humans; Adult; Neurofibromatosis 1; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Disease Progression
PubMed: 36840626
DOI: 10.1093/neuonc/noad033 -
International Journal of Molecular... Apr 2024Glioblastoma (GBM) is the most aggressive malignant primary central nervous system (CNS) tumor and, despite decades of research, it remains a lethal disease with a...
Glioblastoma (GBM) is the most aggressive malignant primary central nervous system (CNS) tumor and, despite decades of research, it remains a lethal disease with a median overall survival of less than two years [...].
Topics: Humans; Glioblastoma; Aggression
PubMed: 38612900
DOI: 10.3390/ijms25074090 -
Biomaterials Nov 2023Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer. Current pharmacological interventions marginally increase the 12-month overall survival...
Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer. Current pharmacological interventions marginally increase the 12-month overall survival of patients with GBM. Among the novel therapeutic strategies being pursued, micro-RNAs, a class of non-coding RNAs, are receiving considerable attention for their regulation of several pathways implicated in tumorigenesis and survival. Notably, microRNA-181a-5p (miR-181a) has consistently been reported to be downregulated in GBM clinical samples, and its overexpression negatively affects tumor growth both in vitro and in vivo. To improve the delivery of miR-181a to GBM cells, we sought to develop a modified lipid-based nanocarrier capable of encapsulating and delivering miR-181a to GBM cells in vitro and in vivo. Optimized ionizable-lipid containing lipid nanoparticles (LNP) were constructed by covering the miR-181a-loaded LNP with alternating layers of miR-181a, poly-l-arginine and hyaluronic acid through the layer-by-layer technique. The resulting hyaluronan-decorated lipid nanoparticles (HA-LNP) targeted GBM cells more efficiently than non-modified LNP and mediated siRNA and miRNA transfection in vitro. Finally, delivery of miR-181a by HA-LNP induced significant cellular death of U87 GBM cells in vitro and delayed tumor growth in an in vivo subcutaneous tumor model.
Topics: Humans; Glioblastoma; Hyaluronic Acid; Cell Line, Tumor; MicroRNAs; Lipids; Cell Proliferation
PubMed: 37778056
DOI: 10.1016/j.biomaterials.2023.122341 -
Biomedical Materials (Bristol, England) Aug 2023Glioblastoma (GBM) is the most aggressive and lethal malignant brain tumor, and it is challenging to cure with surgery and treatment. The prevention of permanent brain... (Review)
Review
Glioblastoma (GBM) is the most aggressive and lethal malignant brain tumor, and it is challenging to cure with surgery and treatment. The prevention of permanent brain damage and tumor invasion, which is the ultimate cause of recurrence, are major obstacles in GBM treatment. Besides, emerging treatment modalities and newer genetic findings are helping to understand and manage GBM in patients. Accordingly, researchers are focusing on advanced nanomaterials-based strategies for tackling the various problems associated with GBM. In this context, researchers explored novel strategies with various alternative treatment approaches such as early detection techniques and theranostics approaches. In this review, we have emphasized the recent advancement of GBM cellular models and their roles in designing GBM therapeutics. We have added a special emphasis on the novel genetic and drug target findings as well as strategies for early detection. Besides, we have discussed various theranostic approaches such as hyperthermia therapy, phototherapy and image-guided therapy. Approaches utilized for targeted drug delivery to the GBM were also discussed. This article also describes the recentandadvances using innovative theranostic approaches.
Topics: Humans; Precision Medicine; Glioblastoma; Hyperthermia, Induced; Phototherapy; Drug Delivery Systems
PubMed: 37582381
DOI: 10.1088/1748-605X/acf0ab -
Journal of Neurosurgery Sep 2023Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well... (Review)
Review
Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well as novel immunotherapies and targeted small-molecule inhibitors through clinical trials and precision medicine approaches. As treatments have advanced, the radiological and clinical assessment of patients with GBM has become even more challenging and nuanced. Advances in spatial resolution and both anatomical and physiological information that can be derived from MRI have greatly improved the noninvasive assessment of GBM before, during, and after therapy. Identification of pseudoprogression (PsP), defined as changes concerning for tumor progression that are, in fact, transient and related to treatment response, is critical for successful patient management. These temporary changes can produce new clinical symptoms due to mass effect and edema. Differentiating this entity from true tumor progression is a major decision point in the patient's management and prognosis. Providers may choose to start an alternative therapy, transition to a clinical trial, consider repeat resection, or continue with the current therapy in hopes of resolution. In this review, the authors describe the invasive and noninvasive techniques neurosurgeons need to be aware of to identify PsP and facilitate surgical decision-making.
Topics: Humans; Glioblastoma; Neurosurgeons; Brain Neoplasms; Disease Progression; Magnetic Resonance Imaging
PubMed: 36790010
DOI: 10.3171/2022.12.JNS222173 -
Medical Oncology (Northwood, London,... Nov 2023Glioblastoma multiforme (GBM), a highly aggressive tumor, poses significant challenges in achieving successful treatment outcomes. Conventional therapeutic modalities... (Review)
Review
Glioblastoma multiforme (GBM), a highly aggressive tumor, poses significant challenges in achieving successful treatment outcomes. Conventional therapeutic modalities including surgery, radiation, and chemotherapy have demonstrated limited efficacy, primarily attributed to the complexities associated with drug delivery to the tumor site and tumor heterogeneity. To address this critical need for innovative therapies, the potential of cancer vaccines utilizing tumor cells and dendritic cells has been explored for GBM treatment. This article provides a comprehensive review of therapeutic vaccinations employing cell-based vaccine strategies for the management of GBM. A meticulous evaluation of 45 clinical trials involving more than 1500 participants revealed that cell-based vaccinations have exhibited favorable safety profiles with minimal toxicity. Moreover, these vaccines have demonstrated modest improvements in overall survival and progression-free survival among patients. However, certain limitations still persist. Notably, there is a need for advancements in the development of potent antigens to evoke immune responses, as well as the optimization of dosage regimens. Consequently, while cell-based vaccinations show promise as a potential therapeutic approach for GBM, further research is imperative to overcome the current limitations. The ultimate objective is to surmount these obstacles and establish cell-based vaccinations as a standard therapeutic modality for GBM.
Topics: Humans; Glioblastoma; Dendritic Cells; Brain Neoplasms; Treatment Outcome; Cancer Vaccines; Immunotherapy
PubMed: 37952224
DOI: 10.1007/s12032-023-02220-5 -
Cancer Reports (Hoboken, N.J.) Oct 2023A form of cancer called astrocytoma can develop in the brain or spinal cord and sometimes causes death. A detailed overview of the precise signaling cascade underlying... (Review)
Review
BACKGROUND
A form of cancer called astrocytoma can develop in the brain or spinal cord and sometimes causes death. A detailed overview of the precise signaling cascade underlying astrocytoma formation has not yet been revealed, although various factors have been investigated. Therefore, our objective was to unravel and summarize our current understanding of molecular genetics and associated signaling pathways with some possible therapeutic strategies for astrocytoma.
RECENT FINDINGS
In general, four different forms of astrocytoma have been identified in individuals, including circumscribed, diffuse, anaplastic, and multiforme glioblastoma, according to a recent literature review. All types of astrocytoma have a direct connection with some oncogenic signaling cascade. Common signaling is MAPK cascade, including Ras-Raf-ERK, up-regulated with activating EGFR/AKT/PTEN/mTOR and PDGFR. Recent breakthrough studies found that BRAF mutations, including KIAA1549: BRAF and BRAF V600E are responsible for astrocytoma progression. Additionally, cancer progression is influenced by mutations in some tumor suppressor genes, such as the Tp53/ATRX and MGMT mutant. As synthetic medications must cross the blood-brain barrier (BBB), modulating signal systems such as miRNA is the primary option for treating patients with astrocytoma. However, available surgery, radiation therapy, and experimental therapies such as adjuvant therapy, anti-angiogenic therapy, and EGFR-targeting antibody drug are the usual treatment for most types of astrocytoma. Similar to conventional anticancer medications, some phytochemicals slow tumor growth by simultaneously controlling several cellular proteins, including those involved in cell cycle regulation, apoptosis, metastatic spread, tyrosine kinase, growth factor receptor, and antioxidant-related proteins.
CONCLUSION
In conclusion, cellular and molecular signaling is directly associated with the development of astrocytoma, and a combination of conventional and alternative therapies can improve the malignancy of cancer patients.
Topics: Humans; Proto-Oncogene Proteins B-raf; Brain Neoplasms; Astrocytoma; Glioblastoma; ErbB Receptors
PubMed: 37675821
DOI: 10.1002/cnr2.1889 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023Recent multi-omics studies, including proteomics, transcriptomics, genomics, and metabolomics have revealed the critical role of post-translational modifications (PTMs)... (Review)
Review
Recent multi-omics studies, including proteomics, transcriptomics, genomics, and metabolomics have revealed the critical role of post-translational modifications (PTMs) in the progression and pathogenesis of Glioblastoma multiforme (GBM). Further, PTMs alter the oncogenic signaling events and offer a novel avenue in GBM therapeutics research through PTM enzymes as potential biomarkers for drug targeting. In addition, PTMs are critical regulators of chromatin architecture, gene expression, and tumor microenvironment (TME), that play a crucial function in tumorigenesis. Moreover, the implementation of artificial intelligence and machine learning algorithms enhances GBM therapeutics research through the identification of novel PTM enzymes and residues. Herein, we briefly explain the mechanism of protein modifications in GBM etiology, and in altering the biologics of GBM cells through chromatin remodeling, modulation of the TME, and signaling pathways. In addition, we highlighted the importance of PTM enzymes as therapeutic biomarkers and the role of artificial intelligence and machine learning in protein PTM prediction.
Topics: Humans; Artificial Intelligence; Glioblastoma; Protein Processing, Post-Translational; Genomics; Biomarkers; Tumor Microenvironment
PubMed: 37858622
DOI: 10.1016/j.bbcan.2023.188999 -
Advances and Technical Standards in... 2024Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these... (Review)
Review
Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these tumors usually occur in childhood, they also rarely present in adult patients, either as a de novo diagnosis or as a delayed recurrence of a pediatric tumor in the setting of a patient that has transitioned into adult services.Due to the rarity of pediatric-like tumors in adults, the literature on these tumor types in adults is often limited to small case series, and treatment decisions are often based on the management plans taken from pediatric studies. However, the biology of these tumors is often different from the same tumors found in children. Likewise, adult patients are often unable to tolerate the side effects of the aggressive treatments used in children-for which there is little or no evidence of efficacy in adults. In this chapter, we review the literature and summarize the clinical, pathological, molecular profile, and response to treatment for the following pediatric tumor types-medulloblastoma, ependymoma, craniopharyngioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, germ cell tumors, choroid plexus tumors, midline glioma, and pleomorphic xanthoastrocytoma-with emphasis on the differences to the adult population.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Medulloblastoma; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38592530
DOI: 10.1007/978-3-031-53578-9_5