Malignant Intracranial Tumors Research Articles

The tumorigenic effect of the high expression of ABRACL in glioma and its potential as a therapeutic target

Gliomas are the most common malignant intracranial tumors, with no effective treatments. Better understanding and identification of novel targets are urgently warranted. Actin-binding Rho activating C-terminal like (ABRACL) has been reported as an oncogene in several cancer types. However, the potential roles of ABRACL in the tumorigenesis of malignant glioma remain unknown. We discovered that ABRACL is highly expressed in different sub-types of gliomas in both CGGA and TCGA databases, which was further validated in glioblastoma cell lines and normal human astrocyte lines. RT-qPCR, Western blotting and immunohistochemistry demonstrated that ABRACL expression in glioma tissues was upregulated along with the increasing WHO grades. Further survival analysis of glioma patients also revealed that the overall survival of patients in the ABRACL high expression level group were significantly shorter than those in the low expression level group. Knockdown of ABRACL inhibited the proliferation, cell migration, invasion and cytodynamics behaviors in glioma cell lines via activating STAT3 signaling, which also induced apoptosis and cell cycle arrest. Conversely, overexpressing ABRACL promoted cell renewing and migration, enabled more flexible cell deformation, supporting ABRACL being a bona fide oncogene. Intracranial orthotopic xenograft experiment further confirmed that ABRACL downregulation significantly suppressed glioma growth. These results have demonstrated that the tumorigenic effect of ABRACL is partly mediated by STAT3, whose expression also correlates with clinical prognosis. ABRACL facilitates glioma malignancy phenotype through regulating the cytoskeleton by activating STAT3 pathway, suggesting that it may represent a potential therapeutic target for glioblastoma.

Effects of coffee and tea consumption on glioma risk: An umbrella review of systematic reviews and meta-analyses

BackgroundCoffee and tea are considered to have some effects on glioma as one of the most prevalent intracranial malignant tumors in adults. However, the precise effect of coffee and tea consumption on glioma is not obvious. This umbrella review aimed to evaluate the impact of tea and coffee consumption on glioma risk. MethodsThree online databases containing Scopus, Web of Science, and PubMed were thoroughly searched from the beginning to February 23, 2024 with no language constraints. Relying on I2 and Q statistics, a random-effect model or a fixed-effect model was applied. The PICO structure was followed as Population (Patients with glioma), Intervention (Coffee and tea consumption), Comparison (Standard treatment or placebo), and Outcome (Risk of glioma). ResultsTotally, seven meta-analyses and systematic reviews contain 23591 patients were included in this umbrella review. Coffee and tea consumption led to significant 15% and 16% reductions in glioma risk, respectively (RR= 0.85; 95% CI: 0.74, 0.98; RR= 0.84; 95% CI: 0.79, 0.89). The results did not change after subgroup analyses. ConclusionThis umbrella review revealed that the coffee and tea consumption may decrease the glioma risk. Consumption of tea and coffee may be considered as dietary strategies against glioma. PROSPERO registration codeCRD42024521525

68Ga]Ga-FAPI-04 PET/CT imaging of a patient with neurosyphilis mimicking intracranial malignant tumor.

68Ga]Ga-FAPI-04 PET/CT imaging of a patient with neurosyphilis mimicking intracranial malignant tumor.

Immunoexpression of Survivin and P53 in the Histological Subtypes of Medulloblastoma: A Cross-Sectional Observational Study.

Medulloblastoma (MB) is a common malignant intracranial neoplasms in children. The treatment and prognosis of this tumor depends on histology and molecular subtypes. Survivin, implicated in various malignancies, may hold prognostic significance. We investigated survivin and p53 immunoreactivity in different histological subtypes in 20 MB cases from January 2018 to June 2021. Immunohistochemistry revealed survivin expression in 75% (15/20) of cases, with cytoplasmic (10 cases), nuclear (four cases), or combined expression (one case). p53 nuclear expression was present in 35% (7/20) of cases. Classical variant MB exhibited predominant p53 and cytoplasmic survivin expression. Given the association of survivin and p53 expression with poor prognosis, especially in the prevalent classical variant, targeted therapies may hold promise for MB treatment advancement.

A novel L-shaped ortho-quinone analog suppresses glioblastoma progression by targeting acceleration of AR degradation and regulating PI3K/AKT pathway

Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA is a fat-soluble active ingredient obtained from Salvia miltiorrhiza, which has an inhibitory effect against various cancers. We designed and synthesized a novel L-shaped ortho-quinone analog TE5 with tanshinone IIA as the lead compound and tested its antitumor activity against GBM. The results indicated that TE5 effectively inhibited the proliferation, migration, and invasion of GBM cells, and demonstrated low toxicity in vitro. We found that TE5 may bind to androgen receptors and promote their degradation through the proteasome. Inhibition of the PI3K/AKT signaling pathway was also observed in TE5 treated GBM cells. Additionally, TE5 arrested the cell cycle at the G2/M phase and induced mitochondria-dependent apoptosis. In vivo experiments further confirmed the anti-tumor activity, safety, and effect on androgen receptor level of TE5 in animal models of GBM. Our results suggest that TE5 may be a potential therapeutic drug to treat GBM.

EPEN-26. DRUG SCREENING IN PATIENT-DERIVED MODELS OF POSTERIOR FOSSA A EPENDYMOMA REVEALS NOVEL PHARMACOLOGICAL VULNERABILITIES

Abstract Ependymoma (EPN) is the third most common malignant intracranial pediatric brain tumor. The most common and aggressive EPN subgroup, posterior fossa ependymoma group A (PFA-EPN), occurs predominantly in younger children and has a 5-year progression free survival of only 33%. Despite progress in the molecular characterization and subtyping of EPN, the standard treatment remains surgery with adjuvant radiation therapy. There is currently no approved role for chemotherapy in PFA-EPN. As such, identifying novel therapies for PFA-EPN is an important unmet medical need. To define therapeutic sensitivities for PFA-EPN, we performed a drug screen on three patient-derived PFA-EPN cell lines. We found that PFA-EPN cell lines were sensitive to several clinically relevant drugs, most notably those targeting epigenetic regulators. This is of a particular interest as a common molecular feature of PFA-EPN is the global reduction of the repressive post-translational histone modification H3K27me3 due to transcriptional EZHIP overexpression or H3 K27M mutations. To further characterize our PFA-EPN cell lines, we performed optical genome mapping analysis, revealing previously undescribed structural variants affecting genes encoding proteins responsible for signaling and transcription. One PFA-EPN sample that showed profound sensitivity to EGFR inhibitors, also had a duplication of a genomic region containing the EGFR ligand encoding genes, AREG, BTC, EREG, and EPGN. We are currently working to validate these results in larger cohorts of PFA-EPN models. Collectively, these findings provide new clues on drugs, signaling and putative therapeutic targets in these rare yet aggressive tumors.

A Combination of Amide Proton Transfer, Tumor Blood Flow, and Apparent Diffusion Coefficient Histogram Analysis Is Useful for Differentiating Malignant from Benign Intracranial Tumors in Young Patients: A Preliminary Study.

To evaluate the amide proton transfer (APT), tumor blood flow (TBF), and apparent diffusion coefficient (ADC) combined diagnostic value for differentiating intracranial malignant tumors (MTs) from benign tumors (BTs) in young patients, as defined by the 2021 World Health Organization classification of central nervous system tumors. Fifteen patients with intracranial MTs and 10 patients with BTs aged 0-30 years underwent MRI with APT, pseudocontinuous arterial spin labeling (pCASL), and diffusion-weighted imaging. All tumors were evaluated through the use of histogram analysis and the Mann-Whitney U test to compare 10 parameters for each sequence between the groups. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. The APT maximum, mean, 10th, 25th, 50th, 75th, and 90th percentiles were significantly higher in MTs than in BTs; the TBF minimum (min) was significantly lower in MTs than in BTs; TBF kurtosis was significantly higher in MTs than in BTs; the ADC min, 10th, and 25th percentiles were significantly lower in MTs than in BTs (all p < 0.05). The APT 50th percentile (0.900), TBF min (0.813), and ADC min (0.900) had the highest area under the curve (AUC) values of the parameters in each sequence. The AUC for the combination of these three parameters was 0.933. The combination of APT, TBF, and ADC evaluated through histogram analysis may be useful for differentiating intracranial MTs from BTs in young patients.

Advances in determining the gross tumor target volume for radiotherapy of brain metastases.

Brain metastases (BMs) are the most prevalent intracranial malignant tumors in adults and are the leading cause of mortality attributed to malignant brain diseases. Radiotherapy (RT) plays a critical role in the treatment of BMs, with local RT techniques such as stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) showing remarkable therapeutic effectiveness. The precise determination of gross tumor target volume (GTV) is crucial for ensuring the effectiveness of SRS/SBRT. Multimodal imaging techniques such as CT, MRI, and PET are extensively used for the diagnosis of BMs and GTV determination. With the development of functional imaging and artificial intelligence (AI) technology, there are more innovative ways to determine GTV for BMs, which significantly improve the accuracy and efficiency of the determination. This article provides an overview of the progress in GTV determination for RT in BMs.

CNS Germ Cell Tumors: Molecular Advances, Significance in Risk Stratification and Future Directions.

Central Nervous System Germ Cell Tumors (CNS GCTs) represent a subtype of intracranial malignant tumors characterized by highly heterogeneous histology. Current diagnostic methods in clinical practice have notable limitations, and treatment strategies struggle to achieve personalized therapy based on patient risk stratification. Advances in molecular genetics, biology, epigenetics, and understanding of the tumor microenvironment suggest the diagnostic potential of associated molecular alterations, aiding risk subgroup identification at diagnosis. Furthermore, they suggest the existence of novel therapeutic approaches targeting chromosomal alterations, mutated genes and altered signaling pathways, methylation changes, microRNAs, and immune checkpoints. Moving forward, further research is imperative to explore the pathogenesis of CNS GCTs and unravel the intricate interactions among various molecular alterations. Additionally, these findings require validation in clinical cohorts to assess their role in the diagnosis, risk stratification, and treatment of patients.

Temporal Muscle Thickness Compared to Functional Scales as a Prognostic Parameter in Patients with Brain Metastases.

Metastases are the most frequent intracranial malignant tumors in adults. While Karnofsky Performance Status (KPS) and Clinical Frailty Scale (CFS) are known to have significant impact on overall survival (OS), temporal muscle thickness (TMT) has been postulated to be a promising new parameter to estimate prognosis. Patients who received a resection of one to three brain metastases in our institution were included. Temporal muscle thickness was measured in preoperative MRI scans according to a standardized protocol. In 199 patients, the mean TMT was 7.5 mm (95CI 7.3-7.7) and the mean OS during follow-up was 31.3 months (95CI 24.2-38.3). There was no significant correlation of TMT and preoperative or follow-up CFS and KPS. While CFS and KPS did significantly correlate with OS (p < 0.001 for each), no correlation was demonstrated for TMT. CFS showed a superior prognostic value compared to KPS. TMT failed to show a significant impact on OS or patient performance, whereas the clinical scales (KPS and CFS) demonstrate a good correlation with OS. Due to its superiority over KPS, we strongly recommend the use of CFS to estimate OS in patients with brain metastases.

Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.

Glioma is the most common type of primary intracranial malignant tumor, and because of its high invasiveness and recurrence, its prognosis remains poor. The present study investigated the biological function of piggyBac transportable element derived 5 (PGBD5) in glioma. Glioma and para-cancerous tissues were obtained from five patients. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of PGBD5. Transwell assay and flow cytometry were used to evaluate cell migration, invasion, apoptosis and cell cycle distribution. In addition, a nude mouse tumor transplantation model was established to study the downstream pathways of PGBD5 and the molecular mechanism was analyzed using transcriptome sequencing. The mRNA and protein expression levels of PGBD5 were increased in glioma tissues and cells. Notably, knockdown of PGBD5 in vitro could inhibit the migration and invasion of glioma cells. In addition, the knockdown of PGBD5 expression promoted apoptosis and caused cell cycle arrest in the G2/M phase, thus inhibiting cell proliferation. Furthermore, in vivo experiments revealed that knockdown of PGBD5 expression could inhibit Ki67 expression and slow tumor growth. Changes in PGBD5 expression were also shown to be closely related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In conclusion, interference with PGBD5 could inhibit the malignant progression of glioma through the PPAR pathway, suggesting that PGBD5 may be a potential molecular target of glioma.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

A novel brain targeting MnOx-based MI-3 nanoplatform for immunogenic cell death initiated high-efficiency antitumor immunity against orthotopic glioblastoma

As the most invasive and lethal primary intracranial malignant tumor, the implementation of immunotherapy to glioblastoma (GBM) is still severely hindered by the limitations of the blood–brain barrier (BBB) and low tumor immunogenicity. Herein, a nanoplatform composed of rabies virus glycoprotein 29 (RVG29)-modified menin-mixed lineage leukemia (MLL) inhibitor (MI-3)-loaded MnOx nanoparticles (MMR NPs) is synthesized for effective GBM therapy through eliciting robust antitumor immune responses. After intravenous injection, MMR NPs can firstly cross the BBB and reach the tumor site due to the existence of RVG29. Then the immunogenic cell death (ICD) of GBM is achieved through MnOx induced reactive oxygen species (ROS) generation and ferroptosis. Meanwhile, MI-3, a specific small molecule inhibitor for MLL-rearranged acute myeloid leukemia, is innovatively applied to GBM treatment and found to further cause robust apoptosis and DNA damage. Collectively, the brain targeted MMR NPs realize high-efficiency tumor growth inhibition and ICD-initiated antitumor immunity activation. This work expands the indications of nanoimmunotherapy to intracranial malignancies and explores the feasibility of transforming “cold” tumors into “hot” tumors strategy for GBM.

Prognostic biomarker HIF1α and its correlation with immune infiltration in gliomas.

Certain glioma subtypes, such as glioblastoma multiforme or low-grade glioma, are common malignant intracranial tumors with high rates of relapse and malignant progression even after standard therapy. The overall survival (OS) is poor in patients with gliomas; hence, effective prognostic prediction is crucial. Herein, the present study aimed to explore the potential role of hypoxia-inducible factor 1 subunit alpha (HIF1α) in gliomas and investigate the association between HIF1α and infiltrating immune cells in gliomas. Data from The Cancer Genome Atlas were evaluated via RNA sequencing, clinicopathological, immunological checkpoint, immune infiltration and functional enrichment analyses. Validation of protein abundance was performed using paraffin-embedded samples from patients with glioma. A nomogram model was created to forecast the OS rates at 1, 3 and 5 years after cancer diagnosis. The association between OS and HIF1α expression was estimated using Kaplan-Meier survival analysis and the log-rank test. Finally, HIF1α expression was validated using western blotting, reverse transcription-quantitative PCR, Cell Counting Kit-8 and Transwell assays. The results demonstrated that HIF1α expression was significantly upregulated in gliomas compared with normal human brain glial cells. Immunohistochemistry staining demonstrated differential expression of the HIF1α protein. Moreover, glioma cell viability and migration were inhibited via HIF1α downregulation. HIF1α impacted DNA replication, cell cycling, DNA repair and the immune microenvironment in glioma. HIF1α expression was also positively associated with several types of immune cells and immunological checkpoints and with neutrophils, plasmacytoid dendritic cells and CD56bright cells. The Kaplan-Meier survival analyses further demonstrated a strong association between high HIF1α expression and poor prognosis in patients with glioma. Analysis of the receiver operating characteristic curves demonstrated that HIF1α expression accurately differentiated paired normal brain cells from tumor tissues. Collectively, these findings suggested the potential for HIF1α to be used as a novel prognostic indicator for patients with glioma and that OS prediction models may help in the future to develop effective follow-up and treatment strategies for these patients.

IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.

Glioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment. TCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan-Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection. Both transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages. IL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.

Prognostic Factors of Survival for Grade 3 Solitary Fibrous Tumor/Hemangiopericytoma: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis

Introduction: Grade 3 solitary fibrous tumor, previously known as anaplastic hemangiopericytoma, is a rare and highly malignant intracranial tumor with a limited understanding of its natural history and treatment outcomes. Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database spanning 2000–2019 to evaluate the clinical characteristics and treatment modalities that influence overall survival in this tumor entity. A cohort of 249 patients with intracranial grade 3 solitary fibrous tumors was identified. Univariate and multivariable Cox proportional hazard models were employed to determine significant prognostic factors for overall survival. Kaplan-Meier models were used to visualize survival curves, and a nomogram was constructed to predict survival probabilities at 6- and 12-month following diagnosis. Results: Our findings indicated that patient age (<65 years), localized or regional disease burden, surgical resection, and radiation therapy were significant predictors of better overall survival. Combination therapies showed improved survival, with surgery and radiation therapy having the most significant impact. However, chemotherapy alone or in combination did not demonstrate a significant survival benefit, likely due to the limited sample size. The nomogram provided personalized prognostic predictions based on significant clinical factors. Conclusions: These data emphasize the importance of surgical resection and radiation therapy in the management of grade 3 solitary fibrous tumors, supporting the use of combination therapies to improve overall survival in this rare and aggressive intracranial neoplasm.

Analysis of the clinical display effect of imaging techniques on the staging of gliomas

Glioma is a primary intracranial malignant tumor, which is difficult to be cured and has the characteristics of easy recurrence and high mortality rate, therefore, it is of great clinical significance to accurately grade glioma before operation. Since biopsy of gliomas is relatively difficult and its accuracy cannot be guaranteed, imaging examination has become an important means of clinical grading of gliomas. This paper, through the literature analysis method, reviews the previous studies of applying imaging methods to grade gliomas in China and abroad and summarizes the main techniques of MRI and CT and their grading effects. Finally, this paper finds that MRI and CT can be used to grade gliomas alone, but both have limitations, while the combined application of MRI and CT has high sensitivity and specificity for the diagnosis and grading of gliomas, which makes up for their respective shortcomings, and is worthy of wide application.

BIOS-05. USING DATA-DRIVEN ANALYTICS TO PREDICT SURVIVAL IN PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA: THE UTILITY OF MACHINE LEARNING IN NEXT-GENERATION NEURO-ONCOLOGY PROGNOSTICATION

Abstract Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a &amp;gt;75% 5-year survival rate, children who survive often have substantial neurological and cognitive sequelae. We aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric medulloblastoma patients. Pediatric patients with a histopathologically confirmed diagnosis of medulloblastoma were extracted from the Surveillance Epidemiology and End RESULTS: database (2000-2019) and split into training and validation cohorts in an 80:20 ratio (Figure 1). The Cox proportional hazards model was used to identify the univariate and multivariate survival predictors. Subsequently, a calculator with those factors was developed to predict 2-, 5-, and 10-year overall survival as well as median survival months for pediatric medulloblastoma patients. The performance of the calculator was determined by discrimination, calibration, and decision curve analysis (DCA). A total of 1,739 pediatric patients with medulloblastoma met the prespecified inclusion criteria. Fourteen variables, including age, sex, race, ethnicity, median household income, county attribute, laterality, histology, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy, were included in the calculator (). The concordance index was 0.757 in the training cohort and 0.762 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots. The DCA curves indicated that the developed model has a good clinical prognostic benefit for pediatric medulloblastoma patients, and could aid prognostication efforts in the clinical setting. An easy-to-use prognostic calculator for a large cohort of pediatric patients with medulloblastoma was established. Future efforts should focus on improving granularity of population-based registries and externally validating the proposed calculator.

Disturbed meningeal lymphatic function associated with malignancy and progression in patients with intracranial malignant tumors

Meningeal lymphatic vessels (mLVs) have proven to bear a relationship with tumor immunity and therapeutic efficacy of intracranial malignant tumors in pre-clinical animal studies. We aimed to explore the association between mLV function and intracranial malignant tumors in clinical participants. The participants were allocated to a control group or a group of patients with intracranial tumors. Dynamic enhanced magnetic resonance was used to evaluate the wash-in and wash-out functions of mLVs around the superior sagittal sinus and the sigmoid sinus. A total of 246 individuals were recruited for our study. The area under curve and wash-in rate of mLVs in the intracranial tumor group were higher than in the control group (2,749 vs. 2,110, p<0.001 and 3.72 vs. 2.87, p<0.001, respectively). The wash-out ratio of mLVs was lower in the intracranial tumor group than in the control group (0.65 vs. 0.73, p<0.001). Decreased wash-out of mLVs was associated with tumor progression (β= -0.118; p<0.001). High-grade glioma and isocitrate dehydrogenase wild type were associated with a lower mLV wash-out function (β= -0.057, p= 0.044 and β= -0.069, p= 0.047, respectively). Intracranial malignant tumors were associated with elevated wash-in function and decreased wash-out function of mLVs. High-grade glioma and isocitrate dehydrogenase wild type were associated with low mLV wash-out function, and long-term decreased mLV wash-out function was a risk factor for tumor progression. There was no funding.

LncBIRC3-OT promotes the malignant progression of glioma by interacting with RELA to upregulate stanniocalcin-1 expression

Glioma is the most common malignant intracranial tumor, accounting for 80 % of all malignant brain tumors. Growing evidence suggests that lncRNAs are involved in the growth, angiogenesis, metastasis, and therapeutic resistance in a variety of tumors, including glioma. In this study, lncBIRC3-OT (NONHSAT159592.1), which is highly expressed in glioma, was screened by RNA-seq method and verified by quantitative reverse transcription polymerase chain reaction. Subsequently, we knocked down the endogenous expression of lncBIRC3-OT in U87 and U251 cells and found that down-regulated lncBIRC3-OT inhibited cell proliferation, colony formation, migration, and invasion. Mechanically, lncBIRC3-OT could guide RELA protein to the stanniocalcin-1 (STC1) promoter, initiate STC1 transcription, and ultimately promote the progression of glioma. Together, these findings suggest that lncBIRC3-OT is an important regulator promoting glioma progression, and may be a promising therapeutic target for glioma.