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Acta Neuropathologica Communications Jun 2024
Topics: X-linked Nuclear Protein; Humans; Brain Neoplasms; Glioma; Histones; Ataxia Telangiectasia Mutated Proteins; Male
PubMed: 38926805
DOI: 10.1186/s40478-024-01818-8 -
Scientific Reports Jun 2024Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized...
Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized treatment strategies. We computed enrichment stemness scores and performed consensus clustering to categorize phenotypes. Subsequently, we constructed a prognostic risk model using weighted gene correlation network analysis (WGCNA), random survival forest regression analysis as well as full subset regression analysis. To validate the expression differences of key genes, we employed experimental methods such as quantitative Polymerase Chain Reaction (qPCR) and assessed cell line proliferation, migration, and invasion. Three subtypes were assigned to patients diagnosed with LGG. Notably, Cluster 2 (C2), exhibiting the poorest survival outcomes, manifested characteristics indicative of the subtype characterized by immunosuppression. This was marked by elevated levels of M1 macrophages, activated mast cells, along with higher immune and stromal scores. Four hub genes-CDCA8, ORC1, DLGAP5, and SMC4-were identified and validated through cell experiments and qPCR. Subsequently, these validated genes were utilized to construct a stemness risk signature. Which revealed that Lower-Grade Glioma (LGG) patients with lower scores were more inclined to demonstrate favorable responses to immune therapy. Our study illuminates the stemness characteristics of gliomas, which lays the foundation for developing therapeutic approaches targeting CSCs and enhancing the efficacy of current immunotherapies. By identifying the stemness subtype and its correlation with prognosis and TME patterns in glioma patients, we aim to advance the development of personalized treatments, enhancing the ability to predict and improve overall patient prognosis.
Topics: Humans; Glioma; Tumor Microenvironment; Prognosis; Biomarkers, Tumor; Neoplastic Stem Cells; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Neoplasm Grading; Male; Cell Line, Tumor; Female; Gene Expression Profiling; Cell Proliferation
PubMed: 38926605
DOI: 10.1038/s41598-024-65717-7 -
Anticancer Research Jul 2024Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective...
BACKGROUND/AIM
Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma.
PATIENTS AND METHODS
A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis.
RESULTS
Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data.
CONCLUSION
High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.
Topics: Humans; YAP-Signaling Proteins; Astrocytoma; Adaptor Proteins, Signal Transducing; Female; Male; Transcription Factors; Brain Neoplasms; Middle Aged; Adult; Neoplasm Grading; Oligodendroglioma; Phosphoproteins; Aged; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Trans-Activators; Young Adult
PubMed: 38925840
DOI: 10.21873/anticanres.17113 -
Anticancer Research Jul 2024Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying...
BACKGROUND/AIM
Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying prognostic factors for progression-free survival (PFS) and overall survival (OS).
PATIENTS AND METHODS
In 102 patients with recurrent glioblastoma following primary treatment with resection or biopsy plus adjuvant chemoradiation, 11 characteristics were retrospectively investigated regarding PFS and OS.
RESULTS
In the multivariate analyses, Karnofsky performance score (KPS) 90-100 at the time of recurrence (p=0.032), maximum cumulative diameter of recurrent lesions ≤40 mm (p=0.002), resection of recurrent glioblastoma (p=0.025), and systemic therapy for recurrent glioblastoma (p=0.025) were significantly associated with improved PFS. In addition, KPS 90-100 (p=0.024), maximum cumulative diameter ≤40 mm (p=0.033), and systemic therapy (p=0.006) were significantly associated with better OS.
CONCLUSION
Our study identified high Karnofsky Performance Status (KPS 90-100), maximum cumulative diameter of recurrent glioblastoma lesions ≤40 mm, and systemic therapy for recurrent glioblastoma as independent predictors of overall survival (OS) and progression-free survival (PFS). These independent prognostic factors may help select the most suitable treatment for individual patients with recurrent glioblastoma, potentially improving patient outcomes.
Topics: Humans; Glioblastoma; Male; Female; Middle Aged; Neoplasm Recurrence, Local; Aged; Prognosis; Brain Neoplasms; Progression-Free Survival; Adult; Retrospective Studies; Karnofsky Performance Status; Aged, 80 and over
PubMed: 38925836
DOI: 10.21873/anticanres.17119 -
Anticancer Research Jul 2024Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma...
BACKGROUND/AIM
Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma therapy; therefore, we aimed to find new drugs among the marketed medicines for brain diseases because of their cerebral migratory property and found lomerizine, used for the treatment of migraine.
MATERIALS AND METHODS
We evaluated the effect of lomerizine and its metabolites against U251 glioblastoma cells and temozolomide-resistant cells, T98G and GB-1, caused by the expression of O(6)-methylguanine-DNA methyltransferase or P-glycoprotein, compared with temozolomide, and combined with it. The mechanism of action was investigated using inhibitors of necrosis or apoptosis.
RESULTS
Lomerizine and its metabolite (M6) inhibited the proliferation of glioblastoma cells with greater potency and efficacy than temozolomide, including against temozolomide-resistant cells. The effects of lomerizine and M6 on glioblastoma were mainly attributed to the inhibition of proliferation because cells were not rescued by cell death inhibitors, such as necrosis or apoptosis inhibitors, although they were slightly rescued by necrostatin-1. Additionally, lomerizine and M6 combined with temozolomide were more effective at inhibiting the proliferation of U251 and GB-1 cells at some doses than single treatments.
CONCLUSION
Lomerizine has been used for migraine treatment because of its brain-penetrating properties without serious side-effects; thus, it might potentially be expected to be used alone for glioblastoma, including temozolomide-resistant glioblastoma, or in combination with temozolomide.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Cell Proliferation; Apoptosis; Temozolomide; Piperazines; Drug Resistance, Neoplasm; Brain Neoplasms; Dacarbazine
PubMed: 38925834
DOI: 10.21873/anticanres.17106 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Brain Neoplasms; T-Lymphocytes; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 38924746
DOI: 10.1056/NEJMc2405721 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Immunotherapy, Adoptive; Brain Neoplasms; T-Lymphocytes; Receptors, Chimeric Antigen; Male
PubMed: 38924745
DOI: 10.1056/NEJMc2405721 -
Pediatrics International : Official... 2024Recently, reports of endoscopic approaches for neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (peripheral neuroblastic tumor; PNTs) have been increasing. This...
BACKGROUND
Recently, reports of endoscopic approaches for neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (peripheral neuroblastic tumor; PNTs) have been increasing. This study aimed to clarify the indications for endoscopic surgery for PNTs.
METHODS
Pediatric patients who underwent endoscopic surgery for PNTs at our institution were included in this study. Image-defined risk factors (IDRFs) were analyzed using preoperative computed tomography (CT).
RESULTS
Twenty-four patients underwent endoscopic surgery for PNTs. The diagnoses included neuroblastoma (n = 11), ganglioneuroma (n = 10), and ganglioneuroblastoma (n = 3). Regarding the tumor site, there were 18 cases of adrenal tumors, five cases of mediastinal tumors, and one case of retroperitoneal tumors. Image-defined risk factors were positive in eight cases (contacted with a renal vessel, n = 6; compression of principal bronchi, n = 2). Complete resection was accomplished in 21 cases (14 of 16 IDRF-negative cases and seven of eight IDRF-positive cases). All patients survived without recurrence during the follow-up period.
CONCLUSIONS
The CT findings of contact with renal vessels and compression of principal bronchi do not seem to be indicators of incomplete resection. An endoscopic approach to PNTs in pediatric patients is feasible with a good prognosis if patients are selected strictly.
Topics: Humans; Male; Female; Child, Preschool; Neuroblastoma; Child; Infant; Ganglioneuroma; Ganglioneuroblastoma; Retrospective Studies; Tomography, X-Ray Computed; Endoscopy; Treatment Outcome; Adolescent; Follow-Up Studies; Adrenal Gland Neoplasms; Mediastinal Neoplasms
PubMed: 38924208
DOI: 10.1111/ped.15754 -
CNS Neuroscience & Therapeutics Jun 2024Despite the extensive neurological symptoms induced by COVID-19 and the identification of SARS-CoV-2 in post-mortem brain samples from COVID-19 patients months after...
INTRODUCTION
Despite the extensive neurological symptoms induced by COVID-19 and the identification of SARS-CoV-2 in post-mortem brain samples from COVID-19 patients months after death, the precise mechanisms of SARS-CoV-2 invasion into the central nervous system remain unclear due to the lack of research models.
METHODS
We collected glioma tissue samples from glioma patients who had a recent history of COVID-19 and examined the presence of the SARS-CoV-2 spike protein. Subsequently, spatial transcriptomic analyses were conducted on normal brain tissues, glioma tissues, and glioma tissues from glioma patients with recent COVID-19 history. Additionally, single-cell sequencing data from both glioma tissues and glioma organoids were collected and analyzed. Glioma organoids were utilized to evaluate the efficacy of potential COVID-19 blocking agents.
RESULTS
Glioma tissues from glioma patients with recent COVID-19 history exhibited the presence of the SARS-CoV-2 spike protein. Differences between glioma tissues from glioma patients who had a recent history of COVID-19 and healthy brain tissues primarily manifested in neuronal cells. Notably, neuronal cells within glioma tissues of COVID-19 history demonstrated heightened susceptibility to Alzheimer's disease, depression, and synaptic dysfunction, indicative of neuronal aberrations. Expressions of SARS-CoV-2 entry factors were confirmed in both glioma tissues and glioma organoids. Moreover, glioma organoids were susceptible to pseudo-SARS-CoV-2 infection and the infections could be partly blocked by the potential COVID-19 drugs.
CONCLUSIONS
Gliomas had inherent traits that render them susceptible to SARS-CoV-2 infection, leading to their representability of COVID-19 neurological symptoms. This established a biological foundation for the rationality and feasibility of utilization of glioma organoids as research and blocking drug testing model in SARS-CoV-2 infection within the central nervous system.
Topics: Humans; Glioma; COVID-19; Organoids; Brain Neoplasms; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Male; Female; Middle Aged; Brain
PubMed: 38923860
DOI: 10.1111/cns.14822 -
Cancer Medicine Jun 2024Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current...
INTRODUCTION
Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies.
PATIENTS AND METHODS
Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age.
RESULTS
The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres.
CONCLUSIONS
The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals.
Topics: Humans; Child; Glioma; Female; Male; Neurosurgical Procedures; Germany; Brain Neoplasms; Adolescent; Child, Preschool; Infant; Neoplasm Grading
PubMed: 38923198
DOI: 10.1002/cam4.7417