Brain Neoplasms ; classification ; genetics ; pathology ; Humans

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.
Brain Neoplasms/pathology ; Brain Neoplasms/genetics* ; Human ; Meningioma/pathology ; Meningioma/genetics* ; Mutation* ; Neoplasm Invasiveness ; Protein p53/genetics*

OBJECTIVEThis overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.

DATA SOURCESUsing the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.

STUDY SELECTIONIn screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.

RESULTSDespite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.

CONCLUSIONSWe discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

In recent years, the development of molecular biology and medicine has prompted the research of gene therapy for brain diseases. In this review, we summarized the current gene therapy approaches of major brain diseases. Against the pathogenesis of major brain diseases, including brain tumors, Parkinson's disease, Alzheimer's disease and cerebrovascular disorders, there are several effective gene therapy strategies. It is no doubt that, gene therapy, as a novel treatment, is of great significance for understanding the causes, as well as comprehensive treatment for brain diseases.
Alzheimer Disease ; genetics ; therapy ; Brain Neoplasms ; genetics ; therapy ; Cerebrovascular Disorders ; genetics ; therapy ; Genetic Therapy ; methods ; Humans ; Parkinson Disease ; genetics ; therapy

OBJECTIVETo investigate the differential gene expression of ependymomas.

METHODSFour fresh samples of ependymomas and 1 of normal brain tissue were collected during operation. The extracted total RNAs were converted as (32)P tagged cDNA probes, which were then hybridized with the Atlas Human Cancer Array, producing the array based hybridization maps following the protocol provided with the kit. A set of special software was applied to the analysis and RT-PCR was performed to test the result.

RESULTIn comparison with the normal brain tissue, there were 31 upregulated gene and 1 downregulated gene in ependymomas, most of which were firstly found to be differentially expressed in this kind of tumor.

CONCLUSIONThe discrepancy of gene expression profiles between ependymomas and normal brain tissues is highly put through and effectively detected with cDNA array, which provides new information for the further research on the molecular mechanisms of this lesion.

Brain ; metabolism ; Brain Neoplasms ; genetics ; Ependymoma ; genetics ; Gene Expression Profiling ; Humans ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo establish malignant progression associated gene expression profiles in human brain glioma.

METHODSThe primary (WHO grade II), recurrent (WHO grade III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected from one single patient. Gene expression of different tumor specimens and normal brain tissue of the same patient was compared by microarrary techniques.

RESULTS197 differentially expressed genes with differential ratio > or = 3 were observed when compared with normal brain tissue. When the specimens (3 tumor, 1 normal brain) were paired with each other, 7 groups containing 489 genes (upregulated 193, downregulated 296) were observed. According to the descending frequency of the 109 genes with known function, they were the genes associated with development, metabolism, differentiation, signal transduction, DNA binding transcription, cellular receptor, immunity, ion-channel transportation, protein translation, cell backbone motion, stress, protooncogene and anti-oncogene and cell apoptosis, respectively.

CONCLUSIONFrom the 197 differentially expressed genes found in one glioma patient experiencing tumor malignant progression, 17 genes screened out by bioinformatics assay, may offer valuable information on molecular mechanisms on genesis and malignant progression of glioma.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Profiling ; Glioma ; genetics ; pathology ; Humans ; Oligonucleotide Array Sequence Analysis

Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.
Humans ; Glioblastoma/genetics* ; Exosomes/metabolism* ; MicroRNAs/metabolism* ; Prognosis ; Cell Proliferation ; Brain Neoplasms/genetics* ; Cell Line, Tumor

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
Brain Neoplasms/therapy* ; Glioma/therapy* ; Humans ; Immunotherapy ; Isocitrate Dehydrogenase/genetics* ; Mutation/genetics* ; Tumor Microenvironment

OBJECTIVESTo study the relationship between promoter methylation and mRNA expressions of EMP3 and PCDH-gamma-A11 genes in human glioma, and to analyze the regulation mechanism of promoter methylation in the progression of glioma.

METHODSThe promoter methylation of EMP3 and PCDH-gamma-A11 was studied by a methylation specific PCR in 88 primary astrocytoma, 10 normal brain tissues and 2 glioma cell lines. The mRNA expressions were detected by real-time PCR in 30 primary glioma and 10 normal brain tissues. The correlations of their promoter methylation, mRNA expressions and clinicopathologic characteristics were analyzed. The promoter methylation were also detected in U251 and SHG-44 cell lines.

RESULTSThe promoter methylation of EMP3 was detected in 42 tumors (47.7%) and the methylation of PCDH-gamma-A11 was detected in 76 tumors (86.4%). Their mRNA expressions were all significantly decreased in different pathological grade astrocytomas compared to the normal brain tissues (P < 0.01). Their expressions were suppressed but could be reactivated by 5-aza-deoxycytidine in U251 and SHG-44 cell lines.

CONCLUSIONSThe promoter methylation of EMP3 and PCDH-gamma-A11 genes may lead to the down-regulation of their mRNA levels in glioma. The promoter methylation and mRNA expressions of EMP3 and PCDH-gamma-A11 are closely related with the malignant development of glioma. The promoter methylation of the two genes may provide clues to evaluation of glioma malignancy as well as its prognosis. It also gives us an insight for future glioma medical therapy with a demethylating agent.

Brain Neoplasms ; genetics ; Cadherins ; genetics ; Cell Line, Tumor ; DNA Methylation ; Glioma ; genetics ; Humans ; Membrane Glycoproteins ; genetics ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; genetics