Abstract The diagnosis and treatment of gliomas have traditionally been both a research hotspot and a challenge in clinical medicine. Intracranial multiple gliomas are rare, and their diagnosis and treatment are often more difficult than those of solitary gliomas. In this article, we report our experience with the diagnosis and treatment of a case of intracranial multiple glioblastomas that closely resembled metastatic tumors in terms of neuroimaging and anatomy. This case may provide a useful reference and insight into the clinical management of this type of disease.

Abstract Background and Aim: Glioma is one of the most prevalent and refractory brain cancers with a high recurrence rate. Current limitations of experimental in vitro models include their inability to remodel the heterogeneity of the parental tumors and their incapacity to effectively reflect antitumor effects and mechanisms observable in vivo. Organoid models, as a new technology developed in recent years, can preserve the histological characteristics, cellular diversity, and gene expression of parental tumors to the fullest extent, thereby delivering more reliable data. This study intends to construct a simple organoid model developed from glioma patient material. Materials and Methods: Glioma samples were taken intraoperatively and cultured in the organoid medium using a continuous horizontal shaker. Sample collection and scientific research were authorized and approved by the Ethics Committee of Kowloon Hospital, China (Approval No. KY-2021-007). Immunofluorescence was applied to identify CD31 and Sox2 protein expression in the organoid model. The differences between primary glioblastomas and transplanted organoid tumors were analyzed by hematoxylin and eosin (H and E) staining. Immunohistochemistry (IHC) and Western blot assay were used to analyze the Sox2, Ki67, and CD31 protein expression levels. Results: The success rate of establishing organoid models was 90.9% in the primary glioblastomas, 75.0% in the WHO Grade III gliomas, and 42.9% in the Grade I–II gliomas. Immunofluorescence demonstrated that in vitro cultured organoids expressed CD31 and Sox2. Similarly, IHC and Western blot assay showed that orthotopically transplanted organoid tumors could exhibit high expressions of Sox2, Ki67, and CD31. There were no significant differences regarding the pathological features of primary glioblastomas and glioma organoid model as judged by H and E staining. Conclusions: This study presents a simple in vitro organoid model established from glioma patient samples. The success rate of constructing an organoid model is correlated with the degree of glioma malignancy. The established organoid model displays original model properties and simplifies the development of new experimental platforms that can support preclinical glioma treatment studies.

Glioblastoma multiforme (GBM) is one of the most aggressive tumors known to occur in the brain. Metabolism is one of the driving factors enabling the successful proliferation of tumor cells, thus increasing the tumor mass. Tumor metabolism is now recognized as a major hallmark of oncogenesis. Since the brain largely relies on its glucose supply for growth, glucose metabolism significantly contributes to oncogenesis in brain cancers. Here, we review the major metabolic pathways seen in normal brain physiology in addition to the Warburg effect, aberrant tricarboxylic acid cycle, and oxidative phosphorylation observed in GBM. We highlight the important differences in glucose metabolism between the normal and cancerous environments. In addition, we provide insights into lactate shuttling, the pentose phosphate pathway, and immune interactions with glucose metabolism, which drive the nutritional pathways in both the normal and cancerous environment.

Glioblastoma (GBM) is characterized by a high recurrence rate, significant heterogeneity, and poor prognosis. While there has been a shift in recent years to focus on molecular phenotyping, there are limited data regarding the relationship between the immune milieu and heterogeneous molecular signatures in GBM. Given the success of immunotherapies in other cancers such as non-small-cell lung cancer and melanoma, there has been a concerted effort to correlate the immune compartment of the GBM tumor microenvironment to clinical outcomes. The aim of this narrative review is to establish the role of immunophenotyping in GBM classification. Major immune cell groups in GBM involve myeloid cells (e.g. myeloid-derived suppressor cells, tumor-associated macrophages and microglia, neutrophils, and dendritic cells), lymphocytes (e.g., T, natural killer, and B-cells), and stromal cells (e.g., fibroblasts, pericytes, and endothelial cells). Understanding the relationships between these different immune cell populations and correlating their roles with the current molecular classification scheme as described in the 2021 World Health Organization criteria may further elucidate patterns of clinical response, especially in light of recent advances in new immunotherapies.

Background and Aim: World Health Organization (WHO) grade 4 glioma is a malignancy of the central nervous system characterized by refractoriness to treatment and a high mortality rate. Isocitrate dehydrogenase (IDH) mutation is a crucial molecular event for the classification of glioma and associated with prognosis and exploring genetic and molecular differences between IDH mutant and wildtype glioma is crucial. The aim of this study was to investigate the prognostic gene between IDH mutant and wildtype WHO grade 4 glioma and its functional significance. Materials and Methods: The mRNA expression profile data of WHO grade 4 glioma were downloaded from the Gene Expression Omnibus and Chinese Glioma Genome Atlas databases. Bioinformatic analysis was performed to identify the differentially expressed genes between IDH1-mutant and wildtype WHO grade 4 glioma. Survival analysis, functional enrichment analysis, immune cell infiltration evaluation, and in vitro experimental validation were conducted to evaluate the prognostic and functional significance of Fras1-related extracellular matrix 3 (FREM3). This study was approved by the Institutional Ethics Committee of Xinqiao Hospital, Third Military Medical University (approval No. 2021-Y068-01). Results: Elevated expression of FREM3 in IDH1-mutant WHO grade 4 astrocytoma predicted favorable prognosis in glioma. FREM3 was negatively associated with epithelial–mesenchymal transition (EMT), angiogenesis, and hypoxia; notably, low expression of FREM3 was associated with a higher degree of immune cell infiltration. In vitro experiments demonstrated that high FREM3 expression might attenuate the process of EMT and cellular proliferation in glioma. Conclusions: The gene FREM3 plays a major role in IDH1-mutant WHO grade 4 glioma and elevated FREM3 predicts a favorable prognosis of glioma. Further investigation on FREM3 is warranted to elucidate the mechanisms underlying the malignant evolution of glioma.

Abstract Gliosarcoma is a rare subtype of glioblastoma with the histological features of both glioblastoma and soft-tissue sarcoma. Triple-negative breast cancer (TNBC) is a special type of breast cancer that is different from other breast cancers. It is characterized by strong invasiveness, high recurrence rate, and poor prognosis. The concurrent occurrence of gliosarcoma and TNBC was rarely seen and reported. A 63-year-old woman with a history of TNBC was found to have an intracranial mass due to headache. Intracranial tumor resection surgery was undergone, and histopathological examination postoperation revealed gliosarcoma. After craniotomy, the patient underwent standard radiotherapy and chemotherapy. Postoperative follow-up observation showed no obvious recurrence of either tumor. In conclusion, gliosarcoma and TNBC are tumors with poor prognosis. It is rare to encounter two types of malignant tumors in the same patient. When we encounter intracranial space-occupying patients with a history of malignant tumors, we should first consider tumor metastasis. When excluding the possibility of cancer metastasis, the possibility of two primary tumors should be considered.

Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Due to the lack of clinical data, there is no standard treatment for GBM in old patients, and the prognosis is poor. We report a case of a 69-year-old female patient diagnosed with GBM who received tumor resection, radiotherapy, and temozolomide combined with tumor-treating fields (TTFields), and the overall survival (OS) of this patient was 13 months. The addition of TTFields to standard chemoradiotherapy may prolong the OS and not exacerbate toxicities in the treatment of old GBM patients. This provides more treatment options for old GBM patients. The study was approved by the Ethics Committee of The First Affiliated Hospital of Soochow University, China (No. 499/2023) on November 28, 2023.