Abstract:Background
Multifocal glioblastoma is a rare type of glioblastoma with worse prognosis. In this article, we aimed to report two cases of classical multifocal glioblastoma.
Case presentation
In case 1, a 47-year-old male presented with dizziness, and once had a sudden loss of consciousness accompanied by convulsion of limbs. Contrast-enhanced MRI showed multiple lesions with heterogeneously ring-enhanced characters in the left hemisphere, diagnosed … Show more
Background:
Glioblastoma multiforme (GBM) is the most common central nervous system malignant tumor in adults with 48.3% of cases. Despite it, the presence of transtentorial spread is uncommon, with few patients reported in the literature. In this study, the authors report a case of GBM transtentorial spread to cerebellopontine angle after resection and adjuvant treatment.
Case Description:
A 55-year-old male patient with GBM, previously submitted to surgical resection and adjuvant treatment with radiotherapy and quemotherapy. Fourteen months after the first surgery, he developed headaches associated with dysphagia and dysphonia. Magnetic resonance imaging showed a recurrence of the left parietal lesion and a new mass in the right cerebellopontine angle. The patient underwent successful surgical resection of both lesions. Chemotherapy was maintained after the surgery.
Conclusion:
To the best of our knowledge, there are few cases of GBM metastasis to the cerebellopontine angle reported in the literature. Surgical management should be considered in cases of intracranial hypertension and patients with good performance status.
Background:
Glioblastoma multiforme (GBM) is the most common central nervous system malignant tumor in adults with 48.3% of cases. Despite it, the presence of transtentorial spread is uncommon, with few patients reported in the literature. In this study, the authors report a case of GBM transtentorial spread to cerebellopontine angle after resection and adjuvant treatment.
Case Description:
A 55-year-old male patient with GBM, previously submitted to surgical resection and adjuvant treatment with radiotherapy and quemotherapy. Fourteen months after the first surgery, he developed headaches associated with dysphagia and dysphonia. Magnetic resonance imaging showed a recurrence of the left parietal lesion and a new mass in the right cerebellopontine angle. The patient underwent successful surgical resection of both lesions. Chemotherapy was maintained after the surgery.
Conclusion:
To the best of our knowledge, there are few cases of GBM metastasis to the cerebellopontine angle reported in the literature. Surgical management should be considered in cases of intracranial hypertension and patients with good performance status.
“…Notably, CAT tumors are invasive and multifocal, while vector cells develop single lesions. Multifocal GBMs are rare and usually associated with worse outcomes compared with single lesion GBMs [ 53 , 54 ], supporting an important role of CAT in the development of more aggressive tumors.…”
Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.
“…2,3 None of these treatments are specific to cell type, 4 and even after all treatments are applied, the survival rate is merely 15 months. 5,6 The blood−brain barrier (BBB) is the biggest biological challenge to overcome in the development of therapies for the treatment of GBM. This semipermeable membrane is highly selective, limiting the blood-borne particles allowed to cross.…”
Section: Introductionmentioning
confidence: 99%
“…Chemotherapeutic drugs such as temozolomide, the most utilized drug for GMB, also cause damage to the DNA. Unfortunately, these therapeutic treatments not only target tumor cells but also destroy healthy brain tissues. , None of these treatments are specific to cell type, and even after all treatments are applied, the survival rate is merely 15 months. , …”
Gene editing has emerged as a therapeutic approach to manipulate the genome for killing cancer cells, protecting healthy tissues, and improving immune response to a tumor. The gene editing tool achaete-scute family bHLH transcription factor 1 CRISPR guide RNA (ASCL1-gRNA) is known to restore neuronal lineage potential, promote terminal differentiation, and attenuate tumorigenicity in glioblastoma tumors. Here, we fabricated a polymeric nonviral carrier to encapsulate ASCL1-gRNA by electrostatic interactions and deliver it into glioblastoma cells across a 3D in vitro model of the blood−brain barrier (BBB). To mimic rabies virus (RV) neurotropism, gene-loaded poly(β-amino ester) nanoparticles are surface functionalized with a peptide derivative of rabies virus glycoprotein (RVG29). The capability of the obtained NPs, hereinafter referred to as RV-like NPs, to travel across the BBB, internalize into glioblastoma cells, and deliver ASCL1-gRNA is investigated in a 3D BBB in vitro model through flow cytometry and CLSM microscopy. The formation of nicotinic acetylcholine receptors in the 3D BBB in vitro model is confirmed by immunochemistry. These receptors are known to bind to RVG29. Unlike Lipofectamine which primarily internalizes and transfects endothelial cells, RV-like NPs are capable to travel across the 3D BBB in vitro model, preferentially internalizing glioblastoma cells, and delivering ASCL1-gRNA at an efficiency of 10%, causing noncytotoxic effects.
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