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1.
Glia ; 71(1): 127-138, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35322459

RESUMO

High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling pathways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvironment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.


Assuntos
Canabinoides , Glioma , Humanos , Adulto , Endocanabinoides/farmacologia , Glioma/patologia , Receptores de Canabinoides/metabolismo , Receptores de Canabinoides/uso terapêutico , Canabinoides/farmacologia , Transdução de Sinais , Microambiente Tumoral
2.
Comput Methods Programs Biomed ; 227: 107233, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36375418

RESUMO

BACKGROUND AND OBJECTIVE: Modeling of glioma growth and evolution is of key importance for cancer diagnosis, predicting clinical progression and improving treatment outcomes of neurosurgery. However, existing models are unable to characterize spatial variations of the proliferation and infiltration of tumor cells, making it difficult to achieve accurate prediction of tumor growth. METHODS: In this paper, a new growth model of brain tumor using a reaction-diffusion equation on brain magnetic resonance images is proposed. Both the heterogeneity of brain tissue and the density of tumor cells are used to estimate the proliferation and diffusion coefficients of brain tumor cells. The diffusion coefficient that characterizes tumor diffusion and infiltration is calculated based on the ratio of tissues (white and gray matter), while the proliferation coefficient is evaluated using the spatial gradient of tumor cells. In addition, a parameter space is constructed using inverse distance weighted interpolation to describe the spatial distribution of proliferation coefficient. RESULTS: The glioma growth predicted by the proposed model were tested by comparing with the real magnetic resonance images of the patients. Experiments and simulation results show that the proposed method achieves accurate modeling of glioma growth. The interpolation-based growth model has higher average dice score of 0.0647 and 0.0545, and higher average Jaccard index of 0.0673 and 0.0573, respectively, compared to the uniform- and gradient-based growth models. CONCLUSIONS: The experimental results demonstrate the feasibility of calculating the proliferation and diffusion coefficients of the growth model based on patient-specific anatomy. The parameter space that characterizes spatial distribution of proliferation and diffusion coefficients is established and incorporated into the simulation of glioma growth. It enables to obtain patient-specific models about glioma growth by estimating and calibrating only a few model parameters.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Neoplasias Encefálicas/patologia , Difusão , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
3.
Eur J Cancer ; 177: 120-142, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335782

RESUMO

As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development. In view of these issues, the ninth Paediatric Strategy Forum focused on MAPK inhibitors. Development of MAPK pathway inhibitors to date has been predominantly driven by adult indications such as malignant melanoma. However, these inhibitors may also target unmet needs in paediatric low-grade gliomas, high-grade gliomas, Langerhans cell histiocytosis, juvenile myelomonocytic leukaemia and several other paediatric conditions. Although MAPK inhibitors have demonstrated activity in paediatric cancer, the response rates and duration of responses needs improvement and better documentation. The rapid development and evaluation of combination approaches, based on a deep understanding of biology, is required to optimise responses and to avoid paradoxical tumour growth and other unintended consequences including severe toxicity. Better inhibitors with higher central nervous systempenetration for primary brain tumours and cancers with a propensity for central nervous system metastases need to be studied to determine if they are more effective than agents currently being used, and the optimum duration of therapy with MAPK inhibition needs to be determined. Systematic and coordinated clinical investigations to inform future treatment strategies with MAPK inhibitors, rather than use outside of clinical trials, are needed to fully assess the risks and benefits of these single agents and combination strategies in both front-line and in the refractory/relapse settings. Platform trials could address the investigation of multiple similar products and combinations. Accelerating the introduction of MAPK inhibitors into front-line paediatric studies is a priority, as is ensuring that these studies generate data appropriate for scientific and regulatory purposes. Early discussions with regulators are crucial, particularly if external controls are considered as randomised control trials in small patient populations can be challenging. Functional end-points specific to the populations in which they are studied, such as visual acuity, motor and neuro psychological function are important, as these outcomes are often more reflective of benefit for lower grade tumours (such as paediatric low-grade glioma and plexiform neurofibroma) and should be included in initial study designs for paediatric low-grade glioma. Early prospective discussions and agreements with regulators are necessary. Long-term follow-up of patients receiving MAPK inhibitors is crucial in view of their prolonged administration and the important involvement of this pathway in normal development. Further rational development, with a detailed understanding of biology of this class of products, is crucial to ensure they provide optimal benefit while minimising toxicity to children and adolescents with cancer.


Assuntos
Glioma , Recidiva Local de Neoplasia , Estados Unidos , Adolescente , Adulto , Criança , Humanos , United States Food and Drug Administration , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Glioma/patologia , Proteínas Quinases Ativadas por Mitógeno
4.
Sci Data ; 9(1): 692, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369198

RESUMO

Diffuse gliomas (DGs) are the most common and lethal primary neoplasms in the central nervous system. The latest 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was published in 2021, immensely changing the approach to diagnosis and decision making. As a part of the Chinese Glioma Genome Atlas (CGGA) project, our aim was to provide genomic profiling of gliomas in a Chinese cohort. Two hundred eighty six gliomas with different grades were collected over the last decade. Using the Illumina HiSeq platform, over 75.8 million high-quality 150 bp paired-end reads were generated per sample, yielding a total of 43.4 billion reads. We also collected each patient's clinical and pathological information and used it to annotate their genetic data. All patients were diagnosed and classified by neuro-pathologist under the 2021 WHO classification. This dataset provides an important reference for researchers and will significantly advance our understanding of gliomas.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Estudos de Coortes , Glioma/genética , Glioma/patologia , Mutação , Organização Mundial da Saúde
5.
Oncogene ; 41(49): 5253-5265, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36316443

RESUMO

Glioma is the most common malignant primary brain tumor with aggressiveness and poor prognosis. Although extracellular vesicles (EVs)-based cell-to-cell communication mediates glioma progression, the key molecular mediators of this process are still not fully understood. Herein, we elucidated an EVs-mediated transfer of suprabasin (SBSN), leading to the aggressiveness and progression of glioma. High levels of SBSN were positively correlated with clinical grade, predicting poor clinical prognosis of patients. Upregulation of SBSN promoted, while silencing of SBSN suppressed tumorigenesis and aggressiveness of glioma cells in vivo. EVs-mediated transfer of SBSN resulted in an increase in SBSN levels, which promoted the aggressiveness of glioma cells by enhancing migration, invasion, and angiogenesis of recipient glioma cells. Mechanistically, SBSN activated NF-κB signaling by interacting with annexin A1, which further induced Lys63-linked and Met1-linear polyubiquitination of NF-κB essential modulator (NEMO). In conclusion, the communication of SBSN-containing EVs within glioma cells drives the formation and development of tumors by activating NF-κB pathway, which may provide potential therapeutic target for clinical intervention in glioma.


Assuntos
Vesículas Extracelulares , Glioma , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Linhagem Celular Tumoral , Glioma/patologia , Ubiquitinação , Vesículas Extracelulares/metabolismo , Antígenos de Diferenciação/metabolismo , Proteínas de Neoplasias/metabolismo
6.
Folia Neuropathol ; 60(3): 338-345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382487

RESUMO

INTRODUCTION: Glioma is a collective term for tumors derived from glial cells and neuronal cells in the nervous system, and is the most common malignant tumor in the brain. Nowadays, the problem of poor treatment effect and high recurrence rate of patients remains to be solved. MATERIAL AND METHODS: In this study, the expression levels of LINC01128 in glioma tissues, cells, and normal control group were determined by real-time quantitative PCR (RT-qPCR). Kaplan-Meier curve was used to evaluate the prognosis and survival. Multivariate Cox analysis was chosen to estimate the prognostic risk factors of glioma. Cell counting kit-8 (CCK-8) and Transwell methods were used to detect the effect of silencing LINC01128 on the proliferation, migration, and invasion of glioma cells, and the targeting effect of LINC01128 on miR-27b-3p was determined based on bio-informatics analysis and luciferase activity detection. RESULTS: LINC01128 was up-regulated in glioma tissues and cells. The possibility of LINC01128 as a prognostic factor of glioma was obtained through Kaplan-Meier's clinical data analysis and multivariate Cox analysis. Silencing LINC01128 targeting miR-27b-3p inhibited the proliferation, migration, and invasion activity of glioma cells. Moreover, there was a negative correlation between LINC01128 and miR-27b-3p. CONCLUSIONS: Silencing LINC01128 inhibited the proliferation, migration, and invasion levels of glioma cells by targeting miR-27b-3p, thereby affecting the progression of gliomas.


Assuntos
Glioma , MicroRNAs , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Glioma/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética
7.
Acta Neurochir (Wien) ; 164(12): 3275-3284, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36331612

RESUMO

BACKGROUND: The focus of clinical management and research in gliomas has been on survival, but the interest in the treatment effects on cognition and health-related quality of life (HRQoL) is emerging. The primary aim of this study was to investigate the dynamics in cognition after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3. The secondary aim was to investigate the association of postoperative changes in cognition with changes HRQoL. METHODS: In this observational study, 48 patients operated for an astrocytoma or oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016-2021, were included. Cognitive and language skills were assessed with a selected test battery and HRQoL was patient-reported as assessed with RAND-36 pre- and approximately 3 months postoperatively. RESULTS: There was a significant postoperative decrease in attention span and verbal learning, but the patients improved in the test for visual memory. There was no change in visual attention, executive function, verbal memory, visual organization and construction, verbal fluency, and confrontation naming. The RAND-36 variables physical function, role physical, general health, vitality, and social functioning decreased significantly after surgery. Patients operated for tumor recurrence exhibited greater deterioration in attention and a greater extent of resection correlated with a less pronounced decrease in verbal memory, but there were otherwise weak associations between the dynamics in cognition and patient-, tumor-, and treatment-variables. A decline in cognitive variables was not associated with worse HRQoL. CONCLUSIONS: Although both several cognitive and HRQoL domains deteriorated postoperatively, these changes did not correlate with each other. This highlights the complexity of cognitive and HRQoL dynamics in the early postoperative phase.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Transtornos Cognitivos , Glioma , Oligodendroglioma , Humanos , Qualidade de Vida , Recidiva Local de Neoplasia , Glioma/patologia , Cognição , Neoplasias Encefálicas/patologia , Testes Neuropsicológicos
8.
Neurocirugia (Astur : Engl Ed) ; 33(6): 356-360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36333093

RESUMO

The WHO classification of tumors of the CNS in 2016 defined "diffuse midline glioma, H3 K27M-mutant" as a new tumor entity locating in the CNS midline. However, the H3 K27M-mutation in "non-midline" glioblastoma are rare and their characteristics have been rarely reported. A 16-year-old girl presented a hyper-intense lesion at her left temporal stem on T2WI, FLAIR and DWI. Biopsy was performed and molecular pathological diagnosis was glioblastoma with H3 K27M-mutant. Accordingly, the possibility of H3 K27M-mutant should be examined not only for diffuse glioma without IDH mutation that develops at a midline location, but also in non-midline locations.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Feminino , Humanos , Adolescente , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Histonas/genética , Mutação , Glioma/patologia
9.
Cells ; 11(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36359771

RESUMO

Histone post-translational modifications modulate gene expression through epigenetic gene regulation. The core histone H3 family members, H3.1, H3.2, and H3.3, play a central role in epigenetics. H3 histones can acquire many post-translational modifications, including the trimethylation of H3K27 (H3K27me3), which represses transcription. Triple methylation of H3K27 is performed by the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component of the Polycomb Repressive Complex 2. Both global increases and decreases in H3K27me3 have been implicated in a wide range of cancer types. Here, we explore how opposing changes in H3K27me3 contribute to cancer by highlighting its role in two vastly different cancer types; (1) a form of glioma known as diffuse midline glioma H3K27-altered and (2) epithelial ovarian cancer. These two cancers vary widely in the age of onset, sex, associated mutations, and cell and organ type. However, both diffuse midline glioma and ovarian cancer have dysregulation of H3K27 methylation, triggering changes to the cancer cell transcriptome. In diffuse midline glioma, the loss of H3K27 methylation is a primary driving factor in tumorigenesis that promotes glial cell stemness and silences tumor suppressor genes. Conversely, hypermethylation of H3K27 occurs in late-stage epithelial ovarian cancer, which promotes tumor vascularization and tumor cell migration. By using each cancer type as a case study, this review emphasizes the importance of H3K27me3 in cancer while demonstrating that the mechanisms of histone H3 modification and subsequent gene expression changes are not a one-size-fits-all across cancer types.


Assuntos
Glioma , Neoplasias Ovarianas , Humanos , Feminino , Histonas/metabolismo , Carcinoma Epitelial do Ovário/genética , Glioma/genética , Glioma/patologia , Metilação de DNA , Epigênese Genética , Neoplasias Ovarianas/genética
10.
Eur Rev Med Pharmacol Sci ; 26(21): 7813-7826, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394729

RESUMO

OBJECTIVE: DEPDC1B, which encodes DEP domain-containing protein 1B, exerts pathogenic effects in diverse cancers, but no such effect has been reported in the case of lower-grade glioma (LGG). Therefore, we sought to investigate the relationship between DEPDC1B expression and the prognosis of patients with LGG and reveal the underlying molecular mechanism. MATERIALS AND METHODS: First, RT-qPCR and immunohistochemical staining were used to examine DEPDC1B mRNA and protein expression in LGG. Second, transcriptomic data were collected from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to investigate the impact of DEPDC1B expression on LGG patients by using the Kaplan-Meier survival analysis, receiver operating characteristic analysis and Cox models. Third, the effects of DEPDC1B on LGG cell proliferation and migration were revealed using wound-healing and Cell Counting Kit-8 assays and Ki67 immunofluorescence staining. Fourth, the Tumor Immune Estimation Resource database was used to examine how DEPDC1B affects the LGG immune microenvironment, and gene set enrichment analysis was used to uncover the signaling pathways in which DEPDC1B is involved in LGG. RESULTS: DEPDC1B was significantly upregulated in both LGG cells and tissues, and high expression of DEPDC1B contributed to poor prognosis of LGG patients and represented an independent risk factor for LGG. Moreover, DEPDC1B knockdown reduced the proliferation and migration abilities of LGG cells. Lastly, DEPDC1B was found to be positively associated with multiple immune infiltrates and immune-checkpoint markers. CONCLUSIONS: Our findings indicate for the first time that DEPDC1B is a pathogenic gene in LGG. More importantly, we provide a new biomarker and immunotherapeutic target for improving the diagnosis and treatment of LGG patients.


Assuntos
Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Prognóstico , Proliferação de Células , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Microambiente Tumoral , Proteínas Ativadoras de GTPase/genética
11.
Biomolecules ; 12(11)2022 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-36358948

RESUMO

BACKGROUND: Glioma is the most common primary tumor of the central nervous system with a high lethality rate. This study aims to mine fibroblast-related genes with prognostic value and construct a corresponding prognostic model. METHODS: A glioma-related TCGA (The Cancer Genome Atlas) cohort and a CGGA (Chinese Glioma Genome Atlas) cohort were incorporated into this study. Variance expression profiling was executed via the "limma" R package. The "clusterProfiler" R package was applied to perform a GO (Gene Ontology) analysis. The Kaplan-Meier (K-M) curve, LASSO regression analysis, and Cox analyses were implemented to determine the prognostic genes. A fibroblast-related risk model was created and affirmed by independent cohorts. We derived enriched pathways between the fibroblast-related high- and low-risk subgroups using gene set variation analysis (GSEA). The immune infiltration cell and the stromal cell were calculated using the microenvironment cell populations-counter (MCP-counter) method, and the immunotherapy response was assessed with the SubMap algorithm. The chemotherapy sensitivity was estimated using the "pRRophetic" R package. RESULTS: A total of 93 differentially expressed fibroblast-related genes (DEFRGs) were uncovered in glioma. Seven prognostic genes were filtered out to create a fibroblast-related gene signature in the TCGA-glioma cohort training set. We then affirmed the fibroblast-related risk model via TCGA-glioma cohort and CGGA-glioma cohort testing sets. The Cox regression analysis proved that the fibroblast-related risk score was an independent prognostic predictor in prediction of the overall survival of glioma patients. The fibroblast-related gene signature revealed by the GSEA was applicable to the immune-relevant pathways. The MCP-counter algorithm results pointed to significant distinctions in the tumor microenvironment between fibroblast-related high- and low-risk subgroups. The SubMap analysis proved that the fibroblast-related risk score could predict the clinical sensitivity of immunotherapy. The chemotherapy sensitivity analysis indicated that low-risk patients were more sensitive to multiple chemotherapeutic drugs. CONCLUSION: Our study identified prognostic fibroblast-related genes and generated a novel risk signature that could evaluate the prognosis of glioma and offer a theoretical basis for clinical glioma therapy.


Assuntos
Biologia Computacional , Glioma , Humanos , Prognóstico , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Fibroblastos/metabolismo , Microambiente Tumoral/genética
12.
Acta Neuropathol Commun ; 10(1): 167, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397144

RESUMO

Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and fluorescence in-situ hybridization. Here, we demonstrate that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to fluorescence in-situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q. Along with detecting the same molecular data obtained from older methods, targeted-next generation sequencing with an RNA sequencing component provides additional information regarding the presence of RNA based alterations that have diagnostic significance and possible therapeutic implications. From this work, we advocate for expanded use of targeted-next generation sequencing over more traditional methods for the detection of important molecular alterations as a part of the standard diagnostic work up for CNS neoplasms.


Assuntos
Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Neuropatologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA , DNA
13.
Neuro Oncol ; 24(Suppl 6): S33-S41, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322098

RESUMO

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/patologia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos/métodos
14.
Neuro Oncol ; 24(Suppl 6): S52-S61, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322101

RESUMO

To aid surgeons in more complete and safe resection of brain tumors, adjuvant technologies have been developed to improve visualization of target tissue. Fluorescence-guided surgery relies on the use of fluorophores and specific light wavelengths to better delineate tumor tissue, inflammation, and areas of blood-brain barrier breakdown. 5-aminolevulinic acid (5-ALA), the first fluorophore developed specifically for brain tumors, accumulates within tumor cells, improving visualization of tumors both at the core, and infiltrative margin. Here, we describe the background of how 5-ALA integrated into the modern neurosurgery practice, clinical evidence for the current use of 5-ALA, and future directions for its role in neurosurgical oncology. Maximal safe resection remains the standard of care for most brain tumors. Gross total resection of high-grade gliomas (HGGs) is associated with greater overall survival and progression-free survival (PFS) in comparison to subtotal resection or adjuvant treatment therapies alone.1-3 A major challenge neurosurgeons encounter when resecting infiltrative gliomas is identification of the glioma tumor margin to perform a radical resection while avoiding and preserving eloquent regions of the brain. 5-aminolevulinic acid (5-ALA) remains the only optical-imaging agent approved by the FDA for use in glioma surgery and identification of tumor tissue.4 A multicenter randomized, controlled trial revealed that 5-ALA fluorescence-guided surgery (FGS) almost doubled the extent of tumor resection and also improved 6-month PFS.5 In this review, we will highlight the current evidence for use of 5-ALA FGS in brain tumor surgery, as well as discuss the future directions for its use.


Assuntos
Neoplasias Encefálicas , Glioma , Cirurgia Assistida por Computador , Humanos , Ácido Aminolevulínico , Glioma/patologia , Neoplasias Encefálicas/patologia , Cirurgia Assistida por Computador/métodos , Procedimentos Neurocirúrgicos/métodos , Corantes Fluorescentes , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
15.
J Clin Neurosci ; 106: 141-144, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327792

RESUMO

Various intraoperative neuroimaging modalities are available to the neurosurgeon during brain tumor surgery. There remains no consensus on which modalities are superior. This retrospective, single-center cohort study directly compares sodium fluorescein (SF) and intraoperative ultrasonography (IOUS) as intraoperative imaging modalities in a sample of patients with glioblastoma isocitrate dehydrogenase 1 wildtype (GBM). Adult patients with GBM who underwent surgical resection using SF or IOUS guidance between 2010 and 2020 were included. Primary outcomes included extent of resection (EOR), post-operative residual tumor volume, gross total resection (GTR) rate, false negative assessments, and the incidence of new post-operative neurologic deficits. Additionally, pre-and post-test probabilities were calculated to assess each modality's ability to identify residual tumor. 98 patients met inclusion criteria (34 SF and 64 IOUS). Mean EOR was significantly higher for SF (94 ± 11 %) when compared to IOUS (87 ± 20 %; p = 0.032). Mean post-operative residual tumor was significantly higher for IOUS (197 ± 358 mm2) when compared to SF (81 ± 161mm2; p = 0.038). GTR was more frequent with SF (62 % vs 46 %, p = 0.12). False negative assessments for residual tumor were more common with IOUS (22 % vs 15 %, p = 0.53). One patient in each group suffered a new neurologic deficit post-operatively (p = 0.58). Sensitivity, specificity, positive predictive value, and negative predictive value were 62 %, 100 %, 100 %, and 81 % for SF and 59 %, 100 %, 100 %, and 67 % for IOUS, respectively. Taken together, SF may be superior to IOUS in maximizing EOR in patients with GBM, however, both modalities appear to have good efficacy.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Fluoresceína , Neoplasia Residual , Estudos Retrospectivos , Estudos de Coortes , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Glioma/patologia , Ultrassonografia , Imageamento por Ressonância Magnética
16.
J Clin Neurosci ; 106: 185-193, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36369078

RESUMO

Due to the tumor itself or its therapy glioma patients may complain on cognitive impairment, while validated neuropsychological testing (NPT) capturing specific neuropsychological domains does not indicate "objective" dysfunction. Little is known on the relevance of this disturbance for patients' everyday life. We aimed to address whether glioma patients treated with state-of-the-art neurosurgical techniques complain on neuropsychological impairment and whether these subjective complaints are disclosed in formal NPT. We assessed both, "objective" and "subjective" neurocognitive functioning in 13 patients with newly diagnosed WHO grade 2 and 3 gliomas, operated between 06/2018 and 12/2020. All underwent both, preoperative and follow-up NPT as well as a semi-structured interview on subjective complaints and specific questionnaires (post-therapeutic) on attention, memory and executive functioning. On group level, no significant changes between preoperative and post-therapeutic NPT occurred. On the individual level, in 3/13 patients new post-therapeutic deficits in objective NPT were detected in specific domains (verbal memory, non-verbal memory, verbal fluency). By contrast, 8/13 patients reported on "subjective" memory impairments post-therapeutically. Furthermore, on specific questionnaires cognitive and emotional executive dysfunction and increased fatigue occurred in patients relative to normative data. Although the findings have to be replicated in larger populations, a discrepancy between "subjective" and "objective" measures was evident. While subjective neurocognitive impairment may simply not represent a true dysfunction, an alternative explanation might be that established standardized NPT is not suitable to detect subtle dysfunction in this population. "Subjective" and "objective" neurocognitive functioning might represent distinct constructs, which should complement each other in patient-centered Neuro-Oncology.


Assuntos
Disfunção Cognitiva , Glioma , Humanos , Autorrelato , Glioma/complicações , Glioma/cirurgia , Glioma/patologia , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Função Executiva , Cognição
17.
Front Immunol ; 13: 1018942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341390

RESUMO

Objective: Increasing studies have indicated that senescence was associated with tumorigenesis and progression. Lower-grade glioma (LGG) presented a less invasive nature, however, its treatment efficacy and prognosis prediction remained challenging due to the intrinsic heterogeneity. Therefore, we established a senescence-related signature and investigated its prognostic role in LGGs. Methods: The gene expression data and clinicopathologic features were from The Cancer Genome Atlas (TCGA) database. The experimentally validated senescence genes (SnGs) from the CellAge database were obtained. Then LASSO regression has been performed to build a prognostic model. Cox regression and Kaplan-Meier survival curves were performed to investigate the prognostic value of the SnG-risk score. A nomogram model has been constructed for outcome prediction. Immunological analyses were further performed. Data from the Chinese Glioma Genome Atlas (CGGA), Repository of Molecular Brain Neoplasia Data (REMBRANDT), and GSE16011 were used for validation. Results: The 6-SnG signature has been established. The results showed SnG-risk score could be considered as an independent predictor for LGG patients (HR=2.763, 95%CI=1.660-4.599, P<0.001). The high SnG-risk score indicated a worse outcome in LGG (P<0.001). Immune analysis showed a positive correlation between the SnG-risk score and immune infiltration level, and the expression of immune checkpoints. The CGGA datasets confirmed the prognostic role of the SnG-risk score. And Kaplan-Meier analyses in the additional datasets (CGGA, REMBRANDT, and GSE16011) validated the prognostic role of the SnG-signature (P<0.001 for all). Conclusion: The SnG-related prognostic model could predict the survival of LGG accurately. This study proposed a novel indicator for predicting the prognosis of LGG and provided potential therapeutic targets.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Glioma/patologia , Neoplasias Encefálicas/patologia , Estimativa de Kaplan-Meier
19.
Zhonghua Bing Li Xue Za Zhi ; 51(11): 1115-1122, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36323540

RESUMO

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis (P>0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients (P<0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.


Assuntos
Glioma , Adulto , Masculino , Feminino , Humanos , Criança , Idoso de 80 Anos ou mais , Hibridização in Situ Fluorescente , Glioma/patologia , Prognóstico , Fusão Gênica , Regiões Promotoras Genéticas
20.
Clin Nucl Med ; 47(12): 1040-1047, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342792

RESUMO

PURPOSE: Dysembryoplastic neuroepithelial tumors (DNETs) are slow-growing epilepsy-associated tumors. Low or normal 11C-methionine (MET) PET uptake helps to differentiate DNETs from other low-grade gliomas. However, diverse MET-PET uptake in DNETs has been observed. The aim of this study is to measure the clinical significance and prognostic value of MET-PET in DNET management. PATIENTS AND METHODS: Retrospective review of 26 DNET patients was done. Clinical characteristics, radiologic findings, and visual and quantitative MET-PET results were analyzed. PET uptake was calculated as the tumor-to-homotopic mirror ratio (TNRm) and tumor-to-contralateral cortex ratio (TNRc). The clinical activity of the tumors at the time of PET was classified into active and quiescent groups. The surgical outcome was defined as a composite of 2 different aspects: tumor progression and/or clinical events such as seizure recurrence or tumor bleeding. RESULTS: Twenty-seven MET-PET examinations (20 initial MET-PET and 7 MET-PET during follow-up) were included. Clinically active tumors at the time of PET presented significantly higher values of TNRm and TNRc than quiescent tumors. High MET-PET uptake by visual grading, TNRm ≥ 1.90, and TNRc ≥ 1.85 exhibited poor prognosis for event-free survival. CONCLUSIONS: MET-PET uptake correlates well with the clinical behavior of DNETs at the time of PET examination. Moreover, High MET-PET uptake is closely related to seizure recurrence if tumors are not entirely resected. Efforts to achieve gross total resection should be made for DNETs with high MET-PET uptake.


Assuntos
Neoplasias Encefálicas , Glioma , Criança , Humanos , Radioisótopos de Carbono , Tomografia por Emissão de Pósitrons/métodos , Glioma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Metionina , Convulsões
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