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2.
Nat Commun ; 15(1): 968, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320988

RESUMO

Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells using a dye uptake methodology, and validate it with recording of cellular calcium epochs and clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, TM-network connectivity correlates with the mesenchymal subtype and dismal patient survival. CHI3L1 gene expression serves as a robust molecular marker of connectivity and functionally influences TM networks. The connectivity signature allows insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients' prognosis, and serves as a robust prognostic biomarker.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioma/genética , Neoplasias Encefálicas/genética , Proteína 1 Semelhante à Quitinase-3
3.
Front Immunol ; 15: 1346585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322268

RESUMO

Glioma, as the most frequently occurring primary malignancy in the central nervous system, significantly impacts patients' quality of life and cognitive abilities. Ferroptosis, a newly discovered form of cell death, is characterized by significant iron accumulation and lipid peroxidation. This process is fundamentally dependent on iron. Various factors inducing ferroptosis can either directly or indirectly influence glutathione peroxidase, leading to reduced antioxidant capabilities and an increase in lipid reactive oxygen species (ROS) within cells, culminating in oxidative cell death. Recent research indicates a strong connection between ferroptosis and a range of pathophysiological conditions, including tumors, neurological disorders, ischemia-reperfusion injuries, kidney damage, and hematological diseases. The regulation of ferroptosis to intervene in the progression of these diseases has emerged as a major area of interest in etiological research and therapy. However, the exact functional alterations and molecular mechanisms underlying ferroptosis remain to be extensively studied. The review firstly explores the intricate relationship between ferroptosis and glioma, highlighting how ferroptosis contributes to glioma pathogenesis and how glioma cells may resist this form of cell death. Then, we discuss recent studies that have identified potential ferroptosis inducers and inhibitors, which could serve as novel therapeutic strategies for glioma. We also examine the current challenges in targeting ferroptosis in glioma treatment, including the complexity of its regulation and the need for precise delivery methods. This review aims to provide a comprehensive overview of the current state of research on ferroptosis in glioma, offering insights into future therapeutic strategies and the broader implications of this novel cell death pathway in cancer biology.


Assuntos
Ferroptose , Glioma , Humanos , Qualidade de Vida , Sistema Nervoso Central , Ferro
4.
Sci Rep ; 14(1): 3118, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326438

RESUMO

In this study, we provide a comprehensive clinical and molecular biological characterization of radiation-induced gliomas (RIG), including a risk assessment for developing gliomas. A cohort of 12 patients who developed RIG 9.5 years (3-31 years) after previous cranial radiotherapy for brain tumors or T-cell acute lymphoblastic leukemia was established. The derived risk of RIG development based on our consecutive cohort of 371 irradiated patients was 1.6% at 10 years and 3.02% at 15 years. Patients with RIG glioma had a dismal prognosis with a median survival of 7.3 months. We described radiology features that might indicate the suspicion of RIG rather than the primary tumor recurrence. Typical molecular features identified by molecular biology examination included the absence of Histon3 mutation, methylation profile of pedHGG-RTK1 and the presence of recurrent PDGFRA amplification and CDKN2A/B deletion. Of the two long-term surviving patients, one had gliomatosis cerebri, and the other had pleomorphic xanthoastrocytoma with BRAF V600E mutation. In summary, our experience highlights the need for tissue diagnostics to allow detailed molecular biological characterization of the tumor, differentiation of the secondary tumor from the recurrence of the primary disease and potentially finding a therapeutic target.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Glioma/genética , Glioma/radioterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Astrocitoma/patologia , Mutação
5.
J Vis Exp ; (203)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38314829

RESUMO

Glioblastoma, IDH-wild type, CNS WHO grade 4 (GBM) is a primary brain tumor associated with poor patient survival despite aggressive treatment. Developing realistic ex vivo models remain challenging. Patient-derived 3-dimensional organoid (PDO) models offer innovative platforms that capture the phenotypic and molecular heterogeneity of GBM, while preserving key characteristics of the original tumors. However, manual dissection for PDO generation is time-consuming, expensive and can result in a number of irregular and unevenly sized PDOs. This study presents an innovative method for PDO production using an automated tissue chopper. Tumor samples from four GBM and one astrocytoma, IDH-mutant, CNS WHO grade 2 patients were processed manually as well as using the tissue chopper. In the manual approach, the tumor material was dissected using scalpels under microscopic control, while the tissue chopper was employed at three different angles. Following culture on an orbital shaker at 37 °C, morphological changes were evaluated using bright field microscopy, while proliferation (Ki67) and apoptosis (CC3) were assessed by immunofluorescence after 6 weeks. The tissue chopper method reduced almost 70% of the manufacturing time and resulted in a significantly higher PDOs mean count compared to the manually processed tissue from the second week onwards (week 2: 801 vs. 601, P = 0.018; week 3: 1105 vs. 771, P = 0.032; and week 4:1195 vs. 784, P < 0.01). Quality assessment revealed similar rates of tumor-cell apoptosis and proliferation for both manufacturing methods. Therefore, the automated tissue chopper method offers a more efficient approach in terms of time and PDO yield. This method holds promise for drug- or immunotherapy-screening of GBM patients.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/patologia , Glioma/patologia , Glioblastoma/patologia , Astrocitoma/patologia , Organoides/patologia
6.
Radiology ; 310(2): e230793, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38319162

RESUMO

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Meníngeas , Meningioma , Adulto , Humanos , Criança , Meios de Contraste , Gadolínio , Fantasia , Inteligência Artificial , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem
7.
Sci Rep ; 14(1): 2822, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38307919

RESUMO

Grade II/III gliomas have a highly heterogeneous clinical course. Identifying prognostic biomarkers in grade II/III gliomas is essential to guide clinical management. We explored epithelial-mesenchymal transition (EMT)-related genes to uncover prognostic features in grade II/III gliomas. Consensus cluster analysis of 200 EMT-related genes classified 512 grade II/III glioma samples into two molecular subtypes, C1 and C2. The C1 subtype had significantly worse overall survival compared to the C2 subtype. Pathway analysis revealed C1 tumors were highly associated with tumor progression pathways and demonstrated higher immune cell infiltration scores. Differential expression analysis identified four genes (ACTN1, AQP1, LAMC3, NRM) that discriminated the two subtypes. Validation in external datasets confirmed that high expression of this four-gene signature predicted poor prognosis in grade II/III gliomas. Cellular experiments showed ACTN1, AQP1 and NRM promoted glioma cell proliferation, migration and invasion. We examined correlations of the signature genes with T cell exhaustion markers and found ACTN1 expression had the strongest association. Immunohistochemistry analysis further demonstrated that ACTN1 protein expression in grade II/III gliomas was negatively correlated with patient overall survival. In summary, our study identified a concise four-gene signature that robustly predicts grade II/III gliomas prognosis across multiple datasets. The signature provides clinical relevance in distinguishing more aggressive grade II/III glioma tumors. Targeting the ACTN1, AQP1 and NRM genes may offer new therapeutic opportunities to improve grade II/III gliomas patient outcomes.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Neoplasias Encefálicas/patologia , Glioma/patologia , Transição Epitelial-Mesenquimal/genética , Laminina
8.
Exp Oncol ; 45(4): 409-420, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38328849

RESUMO

BACKGROUND: To date, no significant clinical progress has been achieved in the treatment of brain malignant gliomas (MG), and the active search for non-invasive circulating biomarkers continues. The prognostic significance of the ratio of the main peripheral blood cell populations of patients with MG is evaluated. Considerable attention is paid to the secretome of platelets (Pt) of peripheral blood. AIM: To evaluate the indicators of the peripheral blood cell population ratios in patients with brain MG and to study the influence of the secretome of Pt (SPt) of the peripheral blood of patients with brain MG in cell cultures in vitro. MATERIALS AND METHODS: We studied samples of peripheral blood from patients with glioma CNS WHO grade G2 (n = 5), G3 (n = 12), and G4 (n = 20). The peripheral blood cell counts were analyzed in the preoperative period on an automatic hematology analyzer. The in vitro study of SPt was performed on the U251 human glioblastoma cell line cultured with SPt from MG patients or SPt pre-incubated with anti-TGF-ß1 antibody. Cell cultures were observed for 72 h, and mitotic index (MI) was calculated. RESULTS: In MG patients, the count of peripheral blood leukocytes and neutrophils increased (p < 0.05). The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) increased by 2-3 times compared to control. Nevertheless, correlation analysis did not reveal significant relationships between quantitative indicators of peripheral blood cells and the tumor malignancy degree in MG patients. The MI in U251 cells increased under the influence of SPt from patients with MG (p < 0.021), correlated with the tumor degree of malignancy (r = 0.246, p = 0.014). Pre-incubation of SPt with anti-TGF-ß1 antibody tends to neutralize this promitotic effect. CONCLUSION: In MG patients, the integral indicators of NLR and SII increased but no significant relationship with the degree of tumor malignancy was found. In U251 cells, promitotic effects of SPt of MG patients partially decreased by anti-TGF-ß1 antibody.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Secretoma , Estudos Retrospectivos , Linfócitos/patologia , Plaquetas/patologia , Glioma/patologia , Prognóstico , Neutrófilos/patologia , Neoplasias Encefálicas/patologia , Inflamação
10.
Eur Rev Med Pharmacol Sci ; 28(2): 679-686, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305610

RESUMO

OBJECTIVE: This study aimed to explore the value of 3.0T magnetic resonance three-dimensional arterial spin labeling imaging (3D-ASL) technology in the differential diagnosis of recurrence and pseudo-progression of high-grade gliomas. PATIENTS AND METHODS: Fifty patients with high-grade glioma were selected as research objects. All 50 patients were examined by magnetic resonance imaging (MRI), and the lesions were found to be enlarged or abnormally enhanced. All the patients were examined using the 3.0T MR 3D-ASL technique. With targeted biopsy pathology as the gold standard, the diagnostic results of the 3.0T MR 3D-ASL technique were analyzed, and the cerebral blood flow (rCBFmax) ratio was compared between patients with recurrent glioma and patients with pseudo-progression [maximum blood flow value/contralateral mirror area (CBFmax/contralateral mirror area), CBFmax/contralateral white matter, CBFmax/contralateral gray matter]. RESULTS: Among 50 glioma patients, 31 (62.00%) were diagnosed with recurrence through pathological examination, and 19 (38.00%) were diagnosed with pseudo-progression. 30 patients with recurrence (60.00%) and 20 patients with pseudo-progression (40.00%) were diagnosed using 3.0T magnetic resonance 3D-ASL technology. The diagnostic accuracy of 3.0T magnetic resonance 3D-ASL technology was 96.77% (30/31) (p > 0.05). Using pathological results as the "gold standard", the relevant parameters of 3.0T magnetic resonance 3D-ASL technology under different pathological results were analyzed. The results showed that the CBFmax/contralateral mirror area, CBFmax/contralateral white matter, and CBFmax/contralateral gray matter ratios of advanced glioma recurrence patients were significantly higher than those of pseudo-progression (p < 0.05). CONCLUSIONS: The application of 3.0T MR 3D-ASL in high-grade glioma can effectively distinguish recurrence and pseudo-progression, with significant diagnostic value.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Gradação de Tumores , Circulação Cerebrovascular
11.
PLoS One ; 19(2): e0291368, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306361

RESUMO

Glioblastoma multiforme (GBM) and the GBM variant gliosarcoma (GS) are among the tumors with the highest morbidity and mortality, providing only palliation. Stem-like glioma cells (SLGCs) are involved in tumor initiation, progression, therapy resistance, and relapse. The identification of general features of SLGCs could contribute to the development of more efficient therapies. Commercially available protein arrays were used to determine the cell surface signature of eight SLGC lines from GBMs, one SLGC line obtained from a xenotransplanted GBM-derived SLGC line, and three SLGC lines from GSs. By means of non-negative matrix factorization expression metaprofiles were calculated. Using the cophenetic correlation coefficient (CCC) five metaprofiles (MPs) were identified, which are characterized by specific combinations of 7-12 factors. Furthermore, the expression of several factors, that are associated with GBM prognosis, GBM subtypes, SLGC differentiation stages, or neural identity was evaluated. The investigation encompassed 24 distinct SLGC lines, four of which were derived from xenotransplanted SLGCs, and included the SLGC lines characterized by the metaprofiles. It turned out that all SLGC lines expressed the epidermal growth factor EGFR and EGFR ligands, often in the presence of additional receptor tyrosine kinases. Moreover, all SLGC lines displayed a neural signature and the IDH1 wildtype, but differed in their p53 and PTEN status. Pearson Correlation analysis identified a positive association between the pluripotency factor Sox2 and the expression of FABP7, Musashi, CD133, GFAP, but not with MGMT or Hif1α. Spherical growth, however, was positively correlated with high levels of Hif1α, CDK4, PTEN, and PDGFRß, whereas correlations with stemness factors or MGMT (MGMT expression and promoter methylation) were low or missing. Factors highly expressed by all SLGC lines, irrespective of their degree of stemness and growth behavior, are Cathepsin-D, CD99, EMMPRIN/CD147, Intß1, the Galectins 3 and 3b, and N-Cadherin.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Gliossarcoma , Humanos , Glioblastoma/metabolismo , Gliossarcoma/genética , Gliossarcoma/metabolismo , Gliossarcoma/patologia , Neoplasias Encefálicas/metabolismo , Recidiva Local de Neoplasia/patologia , Glioma/patologia , Células-Tronco Neoplásicas/metabolismo , Receptores ErbB/metabolismo , Linhagem Celular Tumoral
12.
Sci Adv ; 10(5): eadi9091, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306431

RESUMO

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their complementarity-determining region 3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ and HLA-DR alleles present immunogenic H3K27M epitopes. Furthermore, we identified and profiled H3K27M-reactive B cell receptors from activated B cells in the cerebrospinal fluid. Our results uncover the breadth of the adaptive immune response against a shared clonal neoantigen across multiple HLA allelotypes and support the use of class II-restricted peptide vaccines to stimulate tumor-specific T and B cells harboring receptors with therapeutic potential.


Assuntos
Glioma , Linfócitos T , Humanos , Antígenos HLA-DR , Vacinação , Glioma/genética , Epitopos
13.
Commun Biol ; 7(1): 156, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321118

RESUMO

The hijacking of early developmental programs is a canonical feature of gliomas where neoplastic cells resemble neurodevelopmental lineages and possess mechanisms of stem cell resilience. Given these parallels, uncovering how and when in developmental time gliomagenesis intersects with normal trajectories can greatly inform our understanding of tumor biology. Here, we review how elapsing time impacts the developmental principles of astrocyte (AS) and oligodendrocyte (OL) lineages, and how these same temporal programs are replicated, distorted, or circumvented in pathological settings such as gliomas. Additionally, we discuss how normal gliogenic processes can inform our understanding of the temporal progression of gliomagenesis, including when in developmental time gliomas originate, thrive, and can be pushed towards upon therapeutic coercion.


Assuntos
Glioma , Humanos , Glioma/patologia , Células-Tronco/patologia , Neurogênese , Astrócitos/patologia , Oligodendroglia
14.
Front Immunol ; 15: 1258475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352883

RESUMO

Background: Given the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity. Methods: Based on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET. Results: The expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells. Conclusion: To summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.


Assuntos
Glioma , Exaustão das Células T , Humanos , Antígeno B7-H1 , Inteligência Artificial , Oncogenes , Glioma/genética , Imunidade
15.
CNS Neurosci Ther ; 30(2): e14605, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334007

RESUMO

BACKGROUND: The infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients. METHODS: Comprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK-8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo. RESULTS: HTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α-tubulin to enhance cell migration by decreasing α-tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor-bearing mice. CONCLUSION: Our results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.


Assuntos
Glioma , Tubulina (Proteína) , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Desacetilase 6 de Histona/metabolismo , Tubulina (Proteína)/metabolismo
16.
J Exp Clin Cancer Res ; 43(1): 47, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342925

RESUMO

In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Células Supressoras Mieloides , Humanos , Glioma/patologia , Glioblastoma/patologia , Imunoterapia , Imunomodulação , Microambiente Tumoral , Neoplasias Encefálicas/tratamento farmacológico
17.
Medicine (Baltimore) ; 103(5): e37136, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306557

RESUMO

RATIONALE: Bilateral thalamic glioma is extremely rare and characterized by strictly limited involvement of bilateral thalami. To investigate its clinical and neuroimaging features, we herein reported a rare case of anaplastic astrocytoma (AA) involving both thalami and the brainstem and reviewed the literature. PATIENT CONCERNS: A-33-year-old Chinese woman was referred to our department owing to persistent headache and nausea and vomiting. Neurological examination showed mild cognitive impairment and positive Kernig sign. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated asymmetrical and swollen lesions involving both thalami, midbrain and pontine tegmentum, without restricted diffusion or enhancement. On day 7 after admission, she was transferred to the department of neurosurgery and underwent a stereotactic brain biopsy of the right thalamic lesion. Histopathological features and immunohistochemistry were consistent with AA, IDH wild-type, World Health Organization grade III. INTERVENTIONS: She was administrated with mannitol and glycerin fructose for decreasing intracranial pressure. OUTCOMES: In spite of receiving chemotherapy, she died on 2-month after her initial diagnosis. LESSONS: AA involving in both thalami and brainstem is a rare entity with poor prognosis. The clinicians and radiologists should deepen their awareness of the specific MRI feature of bilateral thalamic involvement. When MRI alone is insufficient, the utility of stereotactic biopsy is essential for making a definitive diagnosis.


Assuntos
Astrocitoma , Neoplasias do Tronco Encefálico , Glioma , Humanos , Feminino , Astrocitoma/patologia , Glioma/patologia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mesencéfalo/patologia
18.
Sci Rep ; 14(1): 3030, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321173

RESUMO

Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan-Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Renais , Carcinoma de Células Escamosas , Neoplasias do Endométrio , Glioblastoma , Glioma , Neoplasias Renais , Neoplasias Pulmonares , Melanoma , Neoplasias da Próstata , Neoplasias Cutâneas , Neoplasias da Glândula Tireoide , Criança , Feminino , Humanos , Masculino , Prognóstico
19.
PLoS One ; 19(2): e0293647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324550

RESUMO

BACKGROUND: Increasing evidence have elucidated that PBX3 played a crucial role in cancer initiation and progression. PBX3 was differentially expressed in many cancer types. However, PBX3 potential involvement in gliomas remains to be explored. METHODS: The expression level of PBX3 in glioma tissues and glioma cells, and its correlation with clinical features were analyzed by data from TCGA, GEPIA, CGGA and CCLE. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. We also analyzed the correlation between PBX3 expression level and survival outcome and survival time of LGG and GBM patients by using linear regression equation. GSEA was used to generate an ordered list of all genes related to PBX3 expression and screening of genes co-expressed with PBX3 mRNA by "limma" package. RESULTS: The results showed that PBX3 was highly expressed in gliomas and its expression increased with the increase of malignancy. Survival analysis found that PBX3 is more valuable in predicting the OS and PFI of LGG patients than that of GBM. For further study, TCGA and CGGA data were downloaded for univariate Cox analysis and multivariate Cox analysis which showed that the expression of PBX3 was independent influencing factors for poor prognosis of LGG patients. Meanwhile, Receiver operating characteristic (ROC) curve showed that PBX3 was a predictor of overall survival rate and progression-free survival rate of LGG. Linear regression model analysis indicated that the higher expression of PBX3 the higher the risk of death of LGG patients, and the higher expression of PBX3 the higher the risk of disease progression of LGG patients. Next, TCGA data were downloaded for GSEA and Co-expression analyses, which was performed to study the function of PBX3. CONCLUSION: PBX3 may be involved in the occurrence and development of glioma, and has potential reference value for the early diagnosis and prediction of prognosis of glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Biomarcadores , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Cognição , Detecção Precoce de Câncer , Glioma/diagnóstico , Glioma/genética , Prognóstico
20.
Neurosurg Focus ; 56(2): E8, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301242

RESUMO

The authors describe the awake surgical mapping of music skills for patients who require resection in brain areas that may support musical abilities. A 65-year-old man was diagnosed with an anterolateral right temporal nonenhancing lesion, likely a diffusely infiltrating glioma, after presenting with several episodes of altered taste and smell and one episode of loss of consciousness. The patient specializes in music and music technology and has composed scores for films. An awake surgery was planned in a semiseated position. Prerecorded melodies were designed preoperatively as a surrogate for a composition skill task. These consisted of 10- to 15-second musical clips played during bipolar electrical stimulation of the overlying cortex and were divided into three segments: listen, play, and accuracy check. During the "listen" phase, the patient listened to a musical prompt. During the "play" phase, he played a musical response on a keyboard. Stimulation at multiple temporal neocortical sites was negative for any alteration in task performance. The patient did well postoperatively with excellent clinical and radiographic results and returned to composing music without functional compromise. Musical composition tasks can be performed safely intraoperatively for patients with musical expertise. Whether stimulating more posterior nondominant temporal neocortex or other cortical or white matter locations can disrupt this task remains undetermined.


Assuntos
Neoplasias Encefálicas , Glioma , Música , Masculino , Humanos , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Vigília , Glioma/cirurgia , Encéfalo , Mapeamento Encefálico/métodos
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