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Neurosurgical Review Jun 2024
Topics: Humans; Glioma; Brain Neoplasms; Meningeal Neoplasms; Neurosurgical Procedures
PubMed: 38922370
DOI: 10.1007/s10143-024-02540-8 -
Current Oncology (Toronto, Ont.) Jun 2024Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk... (Review)
Review
Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk neuroblastoma. Immunotherapy is a promising approach to treat children with this devastating disease. We have previously reported that macrophages are important effector cells in high-risk neuroblastoma. In this perspective article, we discuss the potential function of the macrophage inhibitory receptor SIRPA in the homeostasis of tumor-associated macrophages in high-risk neuroblastoma. The ligand of SIRPA is CD47, known as a "don't eat me" signal, which is highly expressed on cancer cells compared to normal cells. CD47 is expressed on both tumor and stroma cells, whereas SIRPA expression is restricted to macrophages in high-risk neuroblastoma tissues. Notably, high expression is associated with better disease outcome. According to the current paradigm, the interaction between CD47 on tumor cells and SIRPA on macrophages leads to the inhibition of tumor phagocytosis. However, data from recent clinical trials have called into question the use of anti-CD47 antibodies for the treatment of adult and pediatric cancers. The restricted expression of SIRPA on macrophages in many tissues argues for targeting SIRPA on macrophages rather than CD47 in CD47/SIRPA blockade therapy. Based on the data available to date, we propose that disruption of the CD47-SIRPA interaction by anti-CD47 antibody would shift the macrophage polarization status from M1 to M2, which is inferred from the 1998 study by Timms et al. In contrast, the anti-SIRPA F(ab') lacking Fc binds to SIRPA on the macrophage, mimics the CD47-SIRPA interaction, and thus maintains M1 polarization. Anti-SIRPA F(ab') also prevents the binding of CD47 to SIRPA, thereby blocking the "don't eat me" signal. The addition of tumor-opsonizing and macrophage-activating antibodies is expected to enhance active tumor phagocytosis.
Topics: CD47 Antigen; Humans; Neuroblastoma; Receptors, Immunologic; Antigens, Differentiation; Macrophages
PubMed: 38920727
DOI: 10.3390/curroncol31060243 -
Cells Jun 2024The world of cancer treatment is evolving rapidly and has improved the prospects of many cancer patients. Yet, there are still many cancers where treatment prospects... (Review)
Review
The world of cancer treatment is evolving rapidly and has improved the prospects of many cancer patients. Yet, there are still many cancers where treatment prospects have not (or hardly) improved. Glioblastoma is the most common malignant primary brain tumor, and even though it is sensitive to many chemotherapeutics when tested under laboratory conditions, its clinical prospects are still very poor. The blood-brain barrier (BBB) is considered at least partly responsible for the high failure rate of many promising treatment strategies. We describe the workings of the BBB during healthy conditions and within the glioblastoma environment. How the BBB acts as a barrier for therapeutic options is described as well as various approaches developed and tested for passing or opening the BBB, with the ultimate aim to allow access to brain tumors and improve patient perspectives.
Topics: Glioblastoma; Humans; Blood-Brain Barrier; Drug Delivery Systems; Brain Neoplasms; Antineoplastic Agents; Animals
PubMed: 38920629
DOI: 10.3390/cells13120998 -
Annali Italiani Di Chirurgia 2024The aim of our study was to analyze risk factors for postoperative cerebral infarction in patients with glioma in our hospital, and to compare medical imaging techniques...
AIM
The aim of our study was to analyze risk factors for postoperative cerebral infarction in patients with glioma in our hospital, and to compare medical imaging techniques for early diagnosis of postoperative cerebral infarction.
METHODS
A retrospective analysis was conducted on 178 patients (male: 78, female: 100) who underwent glioma surgery at our hospital between May 2015 and October 2023. They were divided into two groups based on the presence of postoperative cerebral infarction within 7 days: the cerebral infarction group (n = 85) and the non-cerebral infarction group (n = 93). Magnetic resonance imaging (MRI) was used to assess the location, distribution, and volume of the tumor before surgery. During the perioperative period, patient postoperative time, intraoperative blood loss, and other relevant data were documented. Computed tomography perfusion (CTP) and diffusion-weighted imaging (DWI) imaging techniques were employed to evaluate the occurrence, area, location, and shape of cerebral infarction. The imaging characteristics of postoperative cerebral infarction were noted. Apparent diffusion coefficient values, apparent diffusion coefficient (ADC) of whole-brain CTP parameters, cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and DWI parameters were measured. The sensitivity and specificity of CTP, DWI, and their combined diagnosis for postoperative cerebral infarction were compared, with consistency assessed using the Kappa value.
RESULTS
This study found that 85 patients (47.8%) experienced postoperative cerebral infarction. Significant risk factors included tumor location in the temporal lobe, tumor volume ≥23.57 cm3, number of surgeries >1, World Health Organization (WHO) grade >3, and intraoperative blood loss >79.83 mL (p < 0.05). Imaging examinations revealed that CTP combined with DWI diagnosis detected cerebral infarctions in 84 patients, showing lower CBF and CBV, and higher TTP, and MTT in the infarct group (p < 0.05). The Kappa values for CTP, DWI, and the combined diagnosis were 0.762, 0.833, and 0.937, respectively (p < 0.001).
CONCLUSIONS
The prevalence of cerebral infarction in patients with glioma is high and is affected by many factors. Timely imaging examination can detect and predict the occurrence of cerebral infarction in patients after surgery, which is of great significance for improving the prognosis of patients.
Topics: Humans; Male; Retrospective Studies; Female; Cerebral Infarction; Middle Aged; Glioma; Brain Neoplasms; Prevalence; Postoperative Complications; Diffusion Magnetic Resonance Imaging; Risk Factors; Aged; Adult; Tomography, X-Ray Computed; Sensitivity and Specificity
PubMed: 38918970
DOI: 10.62713/aic.3275 -
Scientific Reports Jun 2024PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor...
PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor microenvironment remains unclear. The expression profiles of PTBP1 across various cancers were derived from the TCGA, as well as the GTEx and CGGA databases. The CGGA mRNA_325, CGGA mRNA_301, and CGGA mRNA_693 datasets were utilized as validation cohorts. Immune cell infiltration scores were approximated using the TIMER 2.0 tool. Functional enrichment analysis for groups with high and low PTBP1 expression was conducted using Gene Set Enrichment Analysis (GSEA). Methylation data were predominantly sourced from the SMART and Mexpress databases. Linked-omics analysis was employed to perform functional enrichment analysis of genes related to PTBP1 methylation, as well as to conduct protein functional enrichment analysis. Single-cell transcriptome analysis and spatial transcriptome analysis were carried out using Seurat version 4.10. Compared to normal tissues, PTBP1 is significantly overexpressed and hypomethylated in various cancers. It is implicated in prognosis, immune cell infiltration, immune checkpoint expression, genomic variation, tumor neoantigen load, and tumor mutational burden across a spectrum of cancers, with particularly notable effects in low-grade gliomas. In the context of gliomas, PTBP1 expression correlates with WHO grade and IDH1 mutation status. PTBP1 expression and methylation play an important role in a variety of cancers. PTBP1 can be used as a marker of inflammation, progression and prognosis in gliomas.
Topics: Humans; Polypyrimidine Tract-Binding Protein; Heterogeneous-Nuclear Ribonucleoproteins; Prognosis; Biomarkers, Tumor; Glioma; Gene Expression Regulation, Neoplastic; Tumor Microenvironment; DNA Methylation; Gene Expression Profiling; Inflammation; Transcriptome; Brain Neoplasms; Disease Progression; Multiomics
PubMed: 38918441
DOI: 10.1038/s41598-024-64979-5 -
Medical Oncology (Northwood, London,... Jun 2024Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an incurable disease. GBM has a poor prognosis with a median survival of 12-15 months, and its aggressive clinical course is related to rapid growth, extensive infiltration of adjacent tissues, resistance to chemotherapy, radiotherapy and immunotherapy, and frequent relapse. Currently, several molecular biomarkers are used in clinical practice to predict patient prognosis and response to treatment. However, due to the overall unsatisfactory efficacy of standard multimodal treatment and the remaining poor prognosis, there is an urgent need for new biomarkers and therapeutic strategies for GBM. Recent evidence suggests that GBM tumorigenesis is associated with crosstalk between cancer, immune and stromal cells mediated by various cytokines. One of the key factors involved in this process appears to be interleukin-17 (IL-17), a pro-inflammatory cytokine that is significantly upregulated in the serum and tissue of GBM patients. IL-17 plays a key role in tumorigenesis, angiogenesis, and recurrence of GBM by activating pro-oncogenic signaling pathways and promoting cell survival, proliferation, and invasion. IL-17 facilitates the immunomodulation of the tumor microenvironment by promoting immune cells infiltration and cytokine secretion. In this article we review the latest scientific reports to provide an update on the role of IL-17 role in tumorigenesis, tumor microenvironment, diagnosis, prognosis, and treatment of GBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Interleukin-17; Tumor Microenvironment; Biomarkers, Tumor; Prognosis
PubMed: 38918274
DOI: 10.1007/s12032-024-02434-1 -
Seizure Jun 2024The aim of the present study was to review the current knowledge on the neuropathological spectrum of late onset epilepsies. Several terms including 'neuropathology*'... (Review)
Review
The aim of the present study was to review the current knowledge on the neuropathological spectrum of late onset epilepsies. Several terms including 'neuropathology*' AND 'late onset epilepsy' (LOE) combined with distinct neuropathological diagnostic terms were used to search PubMed until November 15, 2023. We report on the relevance of definitional aspects of LOE with implications for the diagnostic spectrum of epilepsies. The neuropathological spectrum in patients with LOE is described and includes vascular lesions, low-grade neuroepithelial neoplasms and focal cortical dysplasias (FCD). Among the latter, the frequency of the FCD subtypes appears to differ between LOE patients and those with seizure onset at a younger age. Neurodegenerative neuropathological changes in the seizure foci of LOE patients require careful interdisciplinary interpretation with respect to the differential diagnosis of primary neurodegenerative changes or epilepsy-related changes. Innate and adaptive neuroinflammation represents an important cause of LOE with intriguing therapeutic options.
PubMed: 38918105
DOI: 10.1016/j.seizure.2024.06.015 -
Frontiers in Immunology 2024Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong... (Review)
Review
Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.
Topics: Humans; Gastrointestinal Microbiome; Glioblastoma; Immune Checkpoint Inhibitors; Brain Neoplasms; Animals; Brain-Gut Axis; Fecal Microbiota Transplantation; Tumor Microenvironment
PubMed: 38915399
DOI: 10.3389/fimmu.2024.1401967 -
Scientific Reports Jun 2024Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a...
Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.
Topics: Humans; Retinoblastoma; Polycomb Repressive Complex 1; Cell Proliferation; Apoptosis; Cell Movement; Animals; Cell Line, Tumor; Mice; Neoplasm Invasiveness; Mice, Nude; Phosphatidylethanolamine Binding Protein; Gene Expression Regulation, Neoplastic; Retinal Neoplasms
PubMed: 38914697
DOI: 10.1038/s41598-024-65011-6 -
Scientific Reports Jun 2024Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in...
Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in medulloblastoma patients. We analyzed data from 2,322 medulloblastoma patients using the SEER database and randomly divided the dataset into training and testing datasets in a 7:3 ratio. We chose three models to build, one based on neural networks (DeepSurv), one based on ensemble learning that Random Survival Forest (RSF), and a typical Cox Proportional-hazards (CoxPH) model. The DeepSurv model outperformed the RSF and classic CoxPH models with C-indexes of 0.751 and 0.763 for the training and test datasets. Additionally, the DeepSurv model showed better accuracy in predicting 1-, 3-, and 5-year survival rates (AUC: 0.767-0.793). Therefore, our prediction model based on deep learning algorithms can more accurately predict the survival rate and survival period of medulloblastoma compared to other models.
Topics: Medulloblastoma; Humans; Deep Learning; Female; Male; SEER Program; Child; Prognosis; Cerebellar Neoplasms; Adolescent; Child, Preschool; Proportional Hazards Models; Survival Rate; Adult; Young Adult; Middle Aged; Neural Networks, Computer; Infant
PubMed: 38914641
DOI: 10.1038/s41598-024-65367-9