Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127.317
Filtrar
1.
Technol Cancer Res Treat ; 23: 15330338241249026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38693845

RESUMO

Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the thermal ablation of target tissue to achieve tumor control with real-time monitoring of the extent by magnetic resonance thermometry, allowing targeted thermal injury to the lesion. Laser Interstitial Thermotherapy has gained interest as a treatment option for recurrent gliomas due to its minimally invasive nature, shorter recovery times, ability to be used even in patients with numerous comorbidities, and potential to provide local tumor control. It can be used as a standalone treatment or combined with other therapies, such as chemotherapy or radiation therapy. We describe the most recent updates regarding several studies and case reports that have evaluated the efficacy and safety of Laser Interstitial Thermotherapy for recurrent gliomas. These studies have reported different outcomes, with some demonstrating promising results in terms of tumor control and patient survival, while others have shown mixed outcomes. The success of Laser Interstitial Thermotherapy depends on various factors, including tumor characteristics, patient selection, and the experience of the surgical team, but the future direction of treatment of recurrent gliomas will include a combined approach, comprising Laser Interstitial Thermotherapy, particularly in deep-seated brain regions. Well-designed prospective studies will be needed to establish with certainty the role of Laser Interstitial Thermotherapy in the treatment of recurrent glioma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Hipertermia Induzida , Terapia a Laser , Recidiva Local de Neoplasia , Humanos , Glioblastoma/terapia , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/terapia , Terapia a Laser/métodos , Neoplasias Encefálicas/terapia , Resultado do Tratamento , Terapia Combinada
2.
J Transl Med ; 22(1): 419, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702818

RESUMO

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.


Assuntos
Apoptose , Proliferação de Células , Glioblastoma , Mitocôndrias , Biogênese de Organelas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Biosens Bioelectron ; 258: 116356, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705073

RESUMO

In this work, the dual-ligand lanthanide metal-organic framework (MOF)-based electrochemiluminescence (ECL) sensor was constructed for the detection of miRNA-128 in glioblastoma (GBM) diagnosis. The luminescent Eu-MOF (EuBBN) was synthesized with terephthalic acid (BDC) and 2-amino terephthalic acid (BDC-NH2) as dual-ligand. Due to the antenna effect, EuBBN with conjugated-π structure exhibited strong luminescent signal and high quantum efficiency, which can be employed as ECL nanoprobe. Furthermore, the novel plasmonic CuS@Au heterostructure array has been prepared. The localized surface plasmon resonance coupling effect of the CuS@Au heterostructure array can amplify the ECL signal of EuBBN significantly. The EuBBN/CuS@Au heterostructure array-based sensing system has been prepared for the detection of miRNA-128 with a wide linear range from 1 fM to 1 nM and a detection limit of 0.24 fM. Finally, miRNA-128 in the clinic GBM tissue sample has been analysis for the distinguish of tumor grade successfully. The results demonstrated that the dual-ligand MOF/CuS@Au heterostructure array-based ECL sensor can provide important support for the development of GBM diagnosis.


Assuntos
Técnicas Biossensoriais , Európio , Glioblastoma , Ouro , Estruturas Metalorgânicas , MicroRNAs , MicroRNAs/análise , Glioblastoma/diagnóstico , Humanos , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Ouro/química , Európio/química , Limite de Detecção , Medições Luminescentes/métodos , Ligantes , Técnicas Eletroquímicas/métodos , Neoplasias Encefálicas/diagnóstico , Ácidos Ftálicos/química , Nanopartículas Metálicas/química , Cobre/química
4.
Clin Neurol Neurosurg ; 241: 108305, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713964

RESUMO

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.


Assuntos
Neoplasias Encefálicas , Conectoma , Imagem de Tensor de Difusão , Estudos de Viabilidade , Glioma , Humanos , Imagem de Tensor de Difusão/métodos , Conectoma/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/cirurgia , Glioma/diagnóstico por imagem , Glioma/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Córtex Motor/diagnóstico por imagem , Córtex Motor/cirurgia , Córtex Motor/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Feminino , Oligodendroglioma/cirurgia , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Astrocitoma/cirurgia , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia
5.
Clin Neurol Neurosurg ; 241: 108304, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718706

RESUMO

OBJECTIVE: Tubular retractors are increasingly used due to their low complication rates, providing easier access to lesions while minimizing trauma from brain retraction. Our study presents the most extensive series of cases performed by a single surgeon aiming to assess the effectiveness and safety of a transcortical-transtubular approach for removing intracranial lesions. METHODS: We performed a retrospective review of patients who underwent resection of an intracranial lesion with the use of tubular retractors. Electronic medical records were reviewed for patient demographics, preoperative clinical deficits, diagnosis, preoperative and postoperative magnetic resonance imaging (MRI) scans, lesion characteristics including location, volume, extent of resection (EOR), postoperative complications, and postoperative deficits. RESULTS: 112 transtubular resections for intracranial lesions were performed. Patients presented with a diverse number of pathologies including metastasis (31.3 %), GBM (21.4 %), and colloid cysts (19.6 %) The mean pre-op lesion volume was 14.45 cm3. A gross total resection was achieved in 81 (71.7 %) cases. Seventeen (15.2 %) patients experienced early complications which included confusion, short-term memory difficulties, seizures, meningitis and motor and visual deficits. Four (3.6 %) patients had permanent complications, including one with aphasia and difficulty finding words, another with memory loss, a third with left-sided weakness, and one patient who developed new-onset long-term seizures. Mean post-operative hospitalization length was 3.8 days. CONCLUSION: Tubular retractors provide a minimally invasive approach for the extraction of intracranial lesions. They serve as an efficient tool in neurosurgery, facilitating the safe resection of deep-seated lesions with minimal complications.


Assuntos
Neoplasias Encefálicas , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto Jovem , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adolescente , Instrumentos Cirúrgicos , Imageamento por Ressonância Magnética
6.
Nat Commun ; 15(1): 3882, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719809

RESUMO

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.


Assuntos
Linfócitos T CD8-Positivos , Vacinas Anticâncer , Carboximetilcelulose Sódica/análogos & derivados , Células Dendríticas , Glioma , Interferons , Poli I-C , Polilisina/análogos & derivados , Humanos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Glioma/imunologia , Glioma/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Poli I-C/administração & dosagem , Poli I-C/farmacologia , Adulto , Receptores Toll-Like/agonistas , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Idoso , Vacinação , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Imunoterapia/métodos , Agonistas do Receptor Semelhante a Toll
7.
BMC Pediatr ; 24(1): 304, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704558

RESUMO

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined. CASE PRESENTATION: A 9-year-old boy with T-ALL had multiple intracranial tumors, which were still detected post early intensification. To investigate residual CNS lesions, we used 11C-methionine (MET)-positron emission tomography. Negative MET uptake in CNS lesions and excellent MRD status in bone marrow allowed continuing therapies without hematopoietic cell transplantation. CONCLUSIONS: In cases with residual lesions on imaging studies, treatment strategies should be considered by the systemic response, direct assessment of spinal fluid, along with further development of noninvasive imaging methods in CNS. Further retrospective or prospective studies are required to determine the prognosis and frequency of cases with residual intracranial lesions after induction therapy.


Assuntos
Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Masculino , Criança , Neoplasias Encefálicas/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomografia por Emissão de Pósitrons , Metionina
8.
ACS Nano ; 18(20): 13266-13276, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38709874

RESUMO

One key challenge in postoperative glioblastoma immunotherapy is to guarantee a potent and durable T-cell response, which is restricted by the immunosuppressive microenvironment within the lymph nodes (LNs). Here, we develop an in situ sprayed exosome-cross-linked gel that acts as an artificial LN structure to directly activate the tumor-infiltrating T cells for prevention of glioma recurrence. Briefly, this gel is generated by a bio-orthogonal reaction between azide-modified chimeric exosomes and alkyne-modified alginate polymers. Particularly, these chimeric exosomes are generated from dendritic cell (DC)-tumor hybrid cells, allowing for direct and robust T-cell activation. The gel structure with chimeric exosomes as cross-linking points avoids the quick clearance by the immune system and thus prolongs the durability of antitumor T-cell immunity. Importantly, this exosome-containing immunotherapeutic gel provides chances for ameliorating functions of antigen-presenting cells (APCs) through accommodating different intracellular-acting adjuvants, such as stimulator of interferon genes (STING) agonists. This further enhances the antitumor T-cell response, resulting in the almost complete elimination of residual lesions after surgery. Our findings provide a promising strategy for postsurgical glioma immunotherapy that warrants further exploration in the clinical arena.


Assuntos
Exossomos , Glioblastoma , Imunoterapia , Linfonodos , Exossomos/química , Glioblastoma/terapia , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Linfonodos/imunologia , Linfonodos/patologia , Animais , Camundongos , Géis/química , Células Dendríticas/imunologia , Linfócitos T/imunologia , Linhagem Celular Tumoral , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Camundongos Endogâmicos C57BL
9.
Aging (Albany NY) ; 16(9): 8306-8319, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38742944

RESUMO

BACKGROUND: Glioblastoma Multiforme (GBM) is one of the most aggressive and fatal brain cancers. The study of metabolites could be crucial for understanding GBM's biology and reveal new treatment strategies. METHODS: The GWAS data for GBM were sourced from the FinnGen database. A total of 1400 plasma metabolites were collected from the GWAS Catalog dataset. The cerebrospinal fluid (CSF) metabolites data were collected from subsets of participants in the WADRC and WRAP studies. We utilized the inverse variance weighting (IVW) method as the primary tool to explore the causal relationship between metabolites in plasma and CSF and glioblastoma, ensuring the exclusion of instances with horizontal pleiotropy. Additionally, four supplementary analytical methods were applied to reinforce our findings. Aberrant results were identified and omitted based on the outcomes of the leave-one-out sensitivity analysis. Conclusively, a reverse Mendelian Randomization analysis was also conducted to further substantiate our results. RESULTS: The study identified 69 plasma metabolites associated with GBM. Of these, 40 metabolites demonstrated a significant positive causal relationship with GBM, while 29 exhibited a significant negative causal association. Notably, Trimethylamine N-oxide (TMAO) levels in plasma, not CSF, were found to be a significant exposure factor for GBM (OR = 3.1627, 95% CI = (1.6347, 6.1189), P = 0.0006). The study did not find a reverse causal relationship between GBM and plasma TMAO levels. CONCLUSIONS: This research has identified 69 plasma metabolites potentially associated with the incidence of GBM, among which TMAO stands out as a promising candidate for an early detectable biomarker for GBM.


Assuntos
Neoplasias Encefálicas , Estudo de Associação Genômica Ampla , Glioblastoma , Análise da Randomização Mendeliana , Humanos , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/sangue , Glioblastoma/genética , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Metilaminas/sangue , Metilaminas/líquido cefalorraquidiano , Feminino , Masculino
10.
Sci Data ; 11(1): 494, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744868

RESUMO

The standard of care for brain tumors is maximal safe surgical resection. Neuronavigation augments the surgeon's ability to achieve this but loses validity as surgery progresses due to brain shift. Moreover, gliomas are often indistinguishable from surrounding healthy brain tissue. Intraoperative magnetic resonance imaging (iMRI) and ultrasound (iUS) help visualize the tumor and brain shift. iUS is faster and easier to incorporate into surgical workflows but offers a lower contrast between tumorous and healthy tissues than iMRI. With the success of data-hungry Artificial Intelligence algorithms in medical image analysis, the benefits of sharing well-curated data cannot be overstated. To this end, we provide the largest publicly available MRI and iUS database of surgically treated brain tumors, including gliomas (n = 92), metastases (n = 11), and others (n = 11). This collection contains 369 preoperative MRI series, 320 3D iUS series, 301 iMRI series, and 356 segmentations collected from 114 consecutive patients at a single institution. This database is expected to help brain shift and image analysis research and neurosurgical training in interpreting iUS and iMRI.


Assuntos
Neoplasias Encefálicas , Bases de Dados Factuais , Imageamento por Ressonância Magnética , Imagem Multimodal , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Ultrassonografia , Neuronavegação/métodos
12.
Dev Neuropsychol ; 49(4): 178-189, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38753032

RESUMO

Tumor-related epilepsy is a common and understudied neurological comorbidity among pediatric temporal lobe tumor patients that poses risk for neurocognitive impairment (NCI). Forty-one youth with either TLT+ (n = 23) or nonneoplastic temporal lobe epilepsy (n = 18) ages 6-20 years completed routine neuropsychological evaluations. Rates of NCI were similar across groups; however, NCI was more common in nonneoplastic participants on a task of phonemic fluency, p = .047. Younger age of seizure onset and greater number of antiseizure medications were associated with NCI among TLT+ participants only. Preliminary findings suggest separate prognostic models of cognitive outcomes between TLT+ and nonneoplastic epilepsy populations may be needed.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Criança , Adolescente , Feminino , Masculino , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/complicações , Adulto Jovem , Neoplasias Encefálicas/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Adulto
13.
Nat Commun ; 15(1): 4241, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762500

RESUMO

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Recidiva Local de Neoplasia , Salmonella typhimurium , Glioblastoma/terapia , Glioblastoma/imunologia , Animais , Camundongos , Salmonella typhimurium/imunologia , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Humanos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Piroptose , Imunidade Adaptativa , Imunidade Inata , Hidrogéis/química , Imunoterapia/métodos
14.
Gulf J Oncolog ; 1(45): 42-48, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38774932

RESUMO

BACKGROUND: The percentage of brain tumor incidence exceeds 50% in the geriatric population admitted at Khoula Hospital (a tertiary care hospital in Oman) as compared to the younger population, furthermore, geriatric patients impose a higher cost of healthcare in general. Therefore, geriatric tumor care is causing a significant burden on the healthcare service in Oman. For this reason, we have developed this study to identify the cost of care for this group. METHODS: Medical data with their costs were collected retrospectively for 108 patients diagnosed with a brain tumor above the age of 65 years and admitted at Khoula Hospital between 2016 and 2019. RESULTS: The two most common diagnoses in terms of incidence were Meningiomas (31.73%) and Glioblastomas (16.34%). Lymphoma peaked with regards to the cost, with an average cost of 8993.83 USD per diagnosis, followed by glioblastoma and then metastatic lesions (with 5039.18 and 4915.76 USD respectively). Of these surgeries, 82.61% were elective, most of which had a cost above or equal to the average. Emergency surgeries showed equal numbers above and below the average cost of surgeries (P< 0.05). The total costs of imaging were 73759.4 USD, with CT (35.8%) + MRI (32.9%) forming 68.7% of the total imaging costs. While laboratory investigation costs totaled 64110.93 USD. CONCLUSION: The cost of tumor care in Oman is variable based on multiple factors. The reported results represent useful information forming the basis for further analysis such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.


Assuntos
Neoplasias Encefálicas , Humanos , Idoso , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Encefálicas/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Idoso de 80 Anos ou mais , Omã
15.
Am Soc Clin Oncol Educ Book ; 44(3): e431450, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723228

RESUMO

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Gradação de Tumores , Humanos , Glioma/genética , Glioma/terapia , Glioma/tratamento farmacológico , Glioma/patologia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Gerenciamento Clínico , Mutação , Terapia de Alvo Molecular
16.
Nat Rev Dis Primers ; 10(1): 33, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724526

RESUMO

Gliomas are primary brain tumours that are thought to develop from neural stem or progenitor cells that carry tumour-initiating genetic alterations. Based on microscopic appearance and molecular characteristics, they are classified according to the WHO classification of central nervous system (CNS) tumours and graded into CNS WHO grades 1-4 from a low to high grade of malignancy. Diffusely infiltrating gliomas in adults comprise three tumour types with distinct natural course of disease, response to treatment and outcome: isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas with the best prognosis; IDH-mutant astrocytomas with intermediate outcome; and IDH-wild-type glioblastomas with poor prognosis. Pilocytic astrocytoma is the most common glioma in children and is characterized by circumscribed growth, frequent BRAF alterations and favourable prognosis. Diffuse gliomas in children are divided into clinically indolent low-grade tumours and high-grade tumours with aggressive behaviour, with histone 3 K27-altered diffuse midline glioma being the leading cause of glioma-related death in children. Ependymal tumours are subdivided into biologically and prognostically distinct types on the basis of histology, molecular biomarkers and location. Although surgery, radiotherapy and alkylating agent chemotherapy are the mainstay of glioma treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways have improved outcome in subsets of patients.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/genética , Glioma/fisiopatologia , Glioma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatologia , Prognóstico , Criança , Isocitrato Desidrogenase/genética , Mutação
17.
Nat Rev Dis Primers ; 10(1): 34, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724549
18.
Neurosurg Rev ; 47(1): 209, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724684

RESUMO

Glioblastoma is a common and aggressive malignant central nervous system tumor in adults. This study aims to evaluate and analyze the scientific results, collaboration countries, main research topics, and topics over time reported about glioblastoma. A bibliometric analysis of glioblastoma publications was performed mainly using R and Multbiplot software for author, journal, and resume. Associated statistic methods Latent Dirichlet Allocation (LDA) and HJ-Biplot. Inclusion criteria were research articles from the PubMed database published in English between 1973 and December 2022. A total of 64,823 documents with an annual growth rate of 8.27% indicates a consistent increase in research output over time. The results for the number of citations and significant publications showed Cancer Res, J Neuro-Oncol, and Neuro-Oncology are the most influential journals in the field of glioblastoma. The countries that concentrated research were the tumor United States, China, Germany, and Italy. Finally, there has been a marked growth in studies on prognosis and patient survival, therapies, and treatments for glioblastoma. These findings reinforce the need for increased global resources to address glioblastoma, particularly in underdeveloped countries. Glioblastoma research's exponential growth reflects sustained interest in early diagnosis and patient survival.


Assuntos
Bibliometria , Neoplasias Encefálicas , Glioblastoma , Glioblastoma/terapia , Humanos , Neoplasias Encefálicas/terapia
19.
J Mol Neurosci ; 74(2): 52, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724832

RESUMO

Treatment of glioblastoma multiforme (GBM) remains challenging. Unraveling the orchestration of glutamine metabolism may provide a novel viewpoint on GBM therapy. The study presented a full and comprehensive comprehending of the glutamine metabolism atlas and heterogeneity in GBM for facilitating the development of a more effective therapeutic choice. Transcriptome data from large GBM cohorts were integrated in this study. A glutamine metabolism-based classification was established through consensus clustering approach, and a classifier by LASSO analysis was defined for differentiating the classification. Prognosis, signaling pathway activity, tumor microenvironment, and responses to immune checkpoint blockade (ICB) and small molecular drugs were characterized in each cluster. A combinational therapy of glutaminase inhibitor CB839 with dihydroartemisinin (DHA) was proposed, and the influence on glutamine metabolism, apoptosis, reactive oxygen species (ROS), and migration was measured in U251 and U373 cells. We discovered that GBM presented heterogeneous glutamine metabolism-based clusters, with unique survival outcomes, activity of signaling pathways, tumor microenvironment, and responses to ICB and small molecular compounds. In addition, the classifier could accurately differentiate the two clusters. Strikingly, the combinational therapy of CB839 with DHA synergistically attenuated glutamine metabolism, triggered apoptosis and ROS accumulation, and impaired migrative capacity in GBM cells, demonstrating the excellent preclinical efficacy. Altogether, our findings unveil the glutamine metabolism heterogeneity in GBM and propose an innovative combination therapy of CB839 with DHA for this malignant disease.


Assuntos
Artemisininas , Neoplasias Encefálicas , Glioblastoma , Glutamina , Glioblastoma/metabolismo , Glioblastoma/tratamento farmacológico , Humanos , Glutamina/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Glutaminase/metabolismo , Glutaminase/antagonistas & inibidores , Microambiente Tumoral , Apoptose , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêutico , Movimento Celular , Benzenoacetamidas/farmacologia , Benzenoacetamidas/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
20.
Radiology ; 311(2): e233120, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713025

RESUMO

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.


Assuntos
Neoplasias Encefálicas , Cromossomos Humanos Par 1 , Glioma , Isocitrato Desidrogenase , Imageamento por Ressonância Magnética , Mutação , Humanos , Isocitrato Desidrogenase/genética , Masculino , Feminino , Adulto , Glioma/genética , Glioma/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagem , Cromossomos Humanos Par 1/genética , Pessoa de Meia-Idade , Cromossomos Humanos Par 19/genética , Meios de Contraste , Deleção Cromossômica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...