bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNSC-02. ANTICANCER ABILITY OF THE BERBERINE TO PROMOTE THE APOPTOSIS EFFECT AND ATTENUATE THE ROS GENERATION CAPACITY ON DBTRG BRAIN CANCER CELLS
Authors: Shen Chiung-Chyi , Yang Meng-Yin , Yang Yi-Chin , Hung Huey-Shan 
Published: November 2024

Abstract
Abstract In this research, berberine (BB), and its effect on the biological performance of DBTRG brain cancer cells and normal endothelial cells (EC) was investigated. Firstly, the DBTRG cancer cell and EC cell were cultured with different concentrations of BB (0.5, 1, 5 and 10 μg/ml), and it was confirmed that BB significantly reduced the proliferation of DBTRG cancer cells. However, there is no significant toxic effect on EC cells. The results of cell cycle analysis confirmed that BB significantly induced DBTRG cancer cell undergo apoptotic effect in a dose dependent manner. The assessment of cell migration behavior showed that BB significantly inhibited cell migration in DBTRG cancer cell, but not in BAEC as well as attenuated the matrix metalloproteinase 2/9 (MMP2/9) in a dose dependent manner. Furthermore, the reactive oxygen species (ROS) generation capacity among DBTRG cancer cell, EC cell and macrophages (Raw 264.7). It was demonstrated that BB was prominently decreased the ROS generation of DBTRG instead of EC or Raw264.7 cell. Moreover, the pro-inflammatory cytokines of TNF-α, IL-1β and IL-6 were significantly inhibited by BB in a dose dependent manner of DBTRG brain cancer cell. As mentioned above, it was demonstrated that bioactive BB molecules is potential for anti-brain cancer drugs may via anti-immune response and anti-oxidative generation capacity for brain cancer therapy. BB biomolecules may target for DBTRG cell which cannot cause inevitable toxic damage to the normal EC cell. Altogether, the promising findings of BB biomolecule on DBTRG cancer cell suggest that BB may be a good candidate of anticancer drug or adjuvant for the treatment of human brain cancer. Key words: berberine, DBTRG brain cancer, anti-immune response, anti-oxidative generation
CNSC-06. NAVIGATING BRAIN CANCER: PATIENT STORIES AND MEDICAL BREAKTHROUGH
Authors: Vanukuru Kiran Deepthi 
Published: November 2024

Abstract
The complex interplay of genetic mutation, dys regulated signalling pathways, Epigenetic modifications and Interaction with tumor microenvironment are the major aggravating factors for Brain Tumors. Neurological complications involve Increased Intracranial pressure, Seizures, Motor and Sensory deficits, Aphasia, Hydrocephaly, Behavioral and personality changes, Cerebellar Symptoms. It is diagnosed in a sequential steps. Collecting good history from patient in primary then examining the patient all through and making some investigations to come to a final diagnosis. On asking history to a patient he complains of recurrent convulsions, Personality changes and some motor activity deficit and loss of few senses. On examination we can reveal defect in cranial nerve functions, Motor or sensory deficits, loss of reflexes and coordination. Then Investigations being the next step for diagnosis, We ask the patient to undergo for a test for Blood Biomarkers and CSF analysis in case of suspection of metastatic Brain tumors. Biopsy to obtain for Histopathological Examination. Histopathological examination is done for analysis of genetic mutations and molecular markers. The other imaging techniques like MRI, MRS, CT, PET, EEG are done. This gives a clear picture of what actually caused tumor and shows a way for treatment. Now the treatment involves both Medical and Surgical treatment. Medical treatment includes Chemotherapy along with radiation therapy where the drugs given are Temozolomide and targeted therapy included EGFR BRAF inhibitors for glioblastoma and low grade gliomas respectively. Tumor treating fields- Optune is given. Surgical treatment involves Craniotomy for removal of primary Brain tumors, Neuro Endoscopy if tumor is present in ventricles or base of Brain, Laser interstitial Thermal therapy for deap seated and recurrent brain tumors. This is all about the treatment and now the patient management is very important for further clinical help. Physical, occupational and speech therapy helps patients recover. Symptomatic approach for inoperable tumors Provide comprehensive support for patients nearing end of life, Emphasise confidence and Quality of life.
CNSC-14. GLIOBLASTOMA MULTIFORME TUMOR VOLUME AND PERSISTENCE OF CHIMERIC ANTIGEN RECEPTOR T CELLS FOLLOWING TREATMENT
Authors: Veerappan Devi , Thomas Reena 
Published: November 2024

Abstract
Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, and lymphoblastic leukemias suggesting benefits in GBM. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure. A radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting (FACS) analysis takes a sample mixture of cells and sorts them into different populations based on specific biomarkers and characteristics. B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume (3.04% Subject 001 with 2438 mm² volume and 2.38% Subject 003 with 224 mm² tumor volume). However, the number of CAR-T cells per 1 mm² was significantly reduced in patients with a larger post-surgical tumor volume (0.0012 cells/mm² Subject 001 and 0.010 cells/mm² Subject 003). This study shows that although there is an overall increased CAR-T cell persistence for a larger tumor volume, the number of CAR-T cells per 1 mm² is significantly smaller for larger tumor volumes, while illustrating that a larger post-surgical tumor bulk volume is correlated with an increased CAR-T cell persistence within 1-week post-infusion. These findings provide novel information and complement other correlative studies as part of the Phase 1 interventional clinical trial for glioblastoma patients.
CNSC-18. A SCOPING REVIEW OF HISTONE 3.3 G34R/V HIGH-GRADE GLIOMA: EPIGENETIC AND MOLECULAR PROFILES, CLINICOPATHOLOGY, AND TREATMENT AVENUES
Authors: Tang Kayen , Cesaire Melissa , McDonald Taylor , Castro Maria , Jackson Sadhana 
Published: November 2024

Abstract
Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for histone 3.3 G34R/V (H3.3G34R/V) mutated gliomas, which often present in adolescent and young adult patients. While treatments to date delay progression, post 5-year overall survival is exceedingly rare. Historically, there has been limited research on H3G34R/V mutant tumors, which likely contributes to lack of advancements in current treatments. This scoping review fills the current knowledge gap of H3G34R/V mutated gliomas and summarizes future targets and therapeutic options. In October 2023, MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection were searched. Two reviewers screened all articles by title and abstract review and three independent reviewers extracted all studies meeting inclusion criteria relevant to H3G34R/V tumors (preclinical and clinical studies). Of the 2203 articles screened, 200 were deemed eligible. The 200 articles included 68 literature reviews, 9 systematic reviews, 54 preclinical studies, and 69 clinically oriented studies. We found that the United States and ACTA neuropathologica are the top country and journal contributors, respectively, to understanding molecular diagnosis, disease pathology, and potential targeted treatment options of H3.3G34R/V tumors. This literature collectively demonstrates the involvement of numerous oncogenes and tumor suppressor genes involved in RAS/MAPK, MYCN, NOTCH, and LIF/STAT pathways such as ATRX, PDGFRA, and TP53 in influencing the neural characteristics and prognostic outcomes of the tumor. While certain therapeutic modalities, including H3K9 methyltransferase inhibitors and bevacizumab-based therapy have exhibited preclinical efficacy and some indication of positive clinical outcomes, more research on agents that permeate the blood-brain barrier to impair growth are necessary. Additionally, further research into the supportive role of the tumor microenvironment that enables disease progression is warranted. Collectively, these studies will empower intelligent prospective clinical trials using H3.3G34R/V targeted therapies which enhance disease survival.
CNSC-21. THE EFFICACY OF TUMOR TREATING FIELDS IN TREATING IDH-MUTANT ASTROCYTOMA, WHO GRADE 4: AN EARLY RESULT FROM SHANGHAI HUASHAN HOSPITAL
Authors: Qiu Xianxin , Chen Lingzhao , Liang Liping , Zhou Zhirui , Liu Jiabing , Zhu Wenjia , Wu Tianqi , Pan Mingyuan , Qin Zhiyong , Wang Yang 
Published: November 2024

Abstract

OBJECTIVES
There is ongoing debate regarding the efficacy of Tumor Treating Fields (TTFields) for treating IDH-mutant grade 4 astrocytoma (IDHmA4). In fact, the evidence supporting TTFields in treating IDHmA4 is largely extrapolated from EF-14, of which the results stem form heterogeneous entities of glioblastoma lack of IDH status. This study was conducted by reviewing the database in our center following the release of WHO CNS 5, aiming to preliminarily explore the efficacy of TTFields and prognosticators of newly-diagnosed IDHmA4.

METHODS
This retrospective analysis included 53 consecutive patients with newly-diagnosed IDHmA4, who underwent radiotherapy at Huashan Hospital, Fudan University between September 2021 and December 2023. All patients were administered with concurrent and adjuvant temozolomide. Eleven patients received adjuvant TTFields after surgery. Information regarding patient baseline characteristics, treatment approaches and molecular markers were collected with the purpose of analyzing prognostic factors.

RESULTS
The median follow-up was 15.7 months. At the time of data cutoff of this analysis, 20 patients had tumor relapse; 3 patients died, all of them were without TTFields therapy. The most common tumor failure pattern was local recurrence (80%, 16/20). The median PFS for the entire cohort was 19.3 months, the median OS was not reached. Univariate analysis indicated that patients who received TTFields therapy tended to have longer median PFS than that of patients without TTFields therapy (24.4 months vs. 18.5 months, P=0.097). Additionally, patients younger than 40 years (24.4 vs. 18.5 months, P=0.107) or without homozygous deletion of CDKN2A/B (23.7 vs. 18.0 months, P=0.108) tended to have better median PFS. No significant independent prognostic factor was found in the multivariate analysis.

CONCLUSIONS
The overall prognosis of IDHmA4 is poor. TTFields may help to improve the outcome of patients with newly-diagnosed IDHmA4. Longer follow-up, larger sample size and prospective clinical trials are warranted for deeper comprehension.
CNSC-22. GLIOBLASTOMA CELLS EXHIBIT NEURON-LIKE EXCITABILITY IN BOTH ACUTE AND ORGANOTYPIC HUMAN BRAIN SLICES
Authors: Tong Tong , Elbæk Kirstine Juul , Eschen Jens , Ozsvar Attila , Cortnum Søren Ole Stigaard , Sindby Ann Kathrine , Kristensen Bjarne Winther , Meier Kaare , Mikic Nikola , Sørensen Jens Christian Hedemann , Capogna Marco , Ting Jonathan , Hou Wen-Hsien , Korshøj Anders Rosendal 
Published: November 2024

Abstract
Glioblastomas (GBM) are known for their significant intratumor heterogeneity, featuring a variety of plastic cell types that make effective treatment challenging. Recent studies have shown that neuronal-progenitor-like transcriptomic cell states at the leading edge of the tumor receive synaptic input from nearby neurons, which drives disease proliferation. However, the excitability of GBM cells remains controversial, with observations ranging from non-excitable to neuron-like excitability, complicating our understanding of their pathophysiology. In this study, we developed a novel experimental approach to study glioblastoma cells in both acute and cultured brain slices infiltrated with cancer from GBM patients. Using an adeno-associated virus for gene delivery, we selectively expressed fluorescent proteins in specific cell types. Fluorescence-guided whole-cell patch-clamp recordings were then used to analyze the electrophysiological properties of GBM cells and neurons within the tumor microenvironment. Our findings show that GBM cells have distinct electrophysiological properties, including a depolarized resting membrane potential (-31.95 ± 2.18 mV, n = 55 cells) and high membrane resistance (1.27 ± 0.19 GΩ, n = 62 cells). Approximately 56% of GBM cells at the tumor’s leading edge exhibited neuron-like excitability, generating aberrant action potentials (aAPs) upon depolarization. Collectively, our study provides direct evidence of the intrinsic excitability of GBM cells and a detailed characterization of their electrophysiological properties in the cancer-infiltrated human cortex. These insights shed new light on tumor heterogeneity and cell-cell interactions in glioblastoma, potentially guiding the development of targeted therapies.
CNSC-24. REAL-TIME HIGH-DENSITY ECOG MAPPING OF SENSORIMOTOR REGIONS AND CONSCIOUSNESS DIFFERENTIATION IN PERI-ROLANDIC GLIOMA SURGERY
Authors: Asman Priscella , Prabhu Sujit , Hall Mathew , Tasnim Israt , Pellizzer Guiseppe , Bhavsar Shyreyas , Tummala Sudhakar , Ince Nuri 
Published: November 2024

Abstract

INTRODUCTION
Accurately mapping sensorimotor regions is crucial for preserving motor and sensory functions in the treatment of gliomas located in the peri-Rolandic areas of the brain.

OBJECTIVE
We examined the use of high-density electrocorticography (ECoG) for passive mapping of sensorimotor regions in treating peri-Rolandic gliomas by analyzing the spatial-temporal and spectral features of real-time somatosensory evoked potentials (SSEPs), and their spectral patterns in differentiating states of consciousness.

METHODS
During surgery, SSEPs were recorded using high-density ECoG on fourteen patients (n=14), both in anesthetized and awake states. Neural data from 0.6Hz median nerve stimulation were captured at 2.4kHz and processed in real-time using MATLAB Simulink. The system displayed SSEPs’ peak activations as a 2D heat map on a screen, particularly around the 20ms time point (N20), and generated the spectral power in the gamma range using the Stockwell transform. Accuracy in delineating the central sulcus (CS) was assessed using the ROC curve, and paired t-tests compared gamma oscillations between states of consciousness.

RESULTS
Patients consistently showed clear discrimination between anterior and posterior channels at the 20ms time point, with 93.6±14.9% accuracy. Color contrast delineated the CS, correlating with the sulcus in the 3D reconstructed magnetic resonance imaging of each patient. Late gamma (60–250 Hz) modulation occurred 50 ms after stimulation onset, extending up to 250 ms in the primary somatosensory area. It was suppressed in the anesthetized state and significantly increased in the awake state (delineation accuracy: 81±10.3% and 91±13.4%, respectively).

CONCLUSIONS
These results demonstrate that SSEPs and gamma modulations can delineate sensorimotor areas and assess consciousness, significantly impacting neurosurgical planning.
CNSC-28. BRAINSTEM NEUROMODULATORY NEURONS PROMOTE GLIOMA GROWTH LOCALLY AND VIA LONG-RANGE PROJECTIONS TO MIDLINE AND CORTICAL STRUCTURES
Authors: Drexler Richard , Drinnenberg Antonia , Gavish Avishai , Yalcin Belgin , Shamardani Kiarash , Rogers Abigail , Mancusi Rebecca , Taylor Kathryn , Kim Yoon Seok , Woo Pamelyn , Ravel Alexandre , Tatlock Eva , Jokhai Rayyan , Ayala-Sarmiento Alberto , Rincon-Fernandez David , Ramakrishnan Charu , La Siverts ’Akea , Daigle Tanya , Tasic Bosiljka , Zeng Hongkui , Breunig Joshua , Loh Kyle , Deisseroth Karl , Monje Michelle 
Published: November 2024

Abstract
Neuronal activity robustly drives glioma progression, mediated through paracrine and synaptic neuron-to-glioma interactions. Recent research has focused on glutamatergic and GABAergic neurons, while the impact of neuromodulatory neuron subpopulations and their long-range projections remain unexplored. Here, we explore the glioma-promoting effects of serotonergic and cholinergic brainstem neurons, which project to defined regions throughout the brain. By employing optogenetic stimulation of midbrain serotonergic or cholinergic neurons in mice bearing high-grade glioma allografts or xenografts, we observed robust, circuit-specific effects of each neuromodulatory neuronal subtype on proliferation. Concordant with the anatomy of serotonergic projections, we found that serotonergic neurons of the dorsal raphe nucleus promoted glioma proliferation in the neocortex and pons, while those from the median raphe nucleus increased proliferation in the thalamus. Similarly, stimulation of cholinergic neurons in the laterodorsal tegmentum nucleus enhanced thalamic glioma growth, and stimulation of the pedunculopontine nucleus promoted pontine tumor growth. The long-range neuronal activity-regulated effects on glioma cells were mediated by neurotransmitter secretion at axon terminals, and paracrine signalling protein release locally in the brainstem. The activity-regulated paracrine factor profiles are distinct between serotonergic and cholinergic neurons, illustrating neuron subtype-specific mechanisms affecting glioma cells beyond neurotransmitter differences. Co-culture with hESC/hiPSC-derived cholinergic or serotonergic neurons demonstrated synaptic structures between both neuromodulatory subpopulations and glioma cells, indicating a synaptic component to these neuron-glioma interactions. ScRNA-seq data integration revealed distinct receptor abundances between DMGs and IDH-WT glioblastomas correlating with specific cellular states. Inhibition of these targets – such as M1 or M3 cholinergic receptors in DMG – mitigated the proliferation-inducing effects of the relevant neuron subtype on glioma cells. In summary, these findings introduce brainstem cholinergic and serotonergic neuromodulatory neurons as drivers of high-grade glioma growth in a circuit-specific manner in midline structures and in neocortex, adding to the complexity with which gliomas integrate into brain-wide neural circuitry.
CNSC-29. CIRCADIAN SIGNALING IN GLIOBLASTOMA SYNCHRONIZES TUMOR DAILY RHYTHMS AND REGULATES TUMOR PROGRESSION
Authors: Gonzalez-Aponte Maria , Damato Anna , Simon Tatiana , Aripova Nigina , Rubin Joshua , Herzog Erik 
Published: November 2024

Abstract
Glioblastoma (GBM) is the most common primary brain tumor in adults with a poor prognosis despite aggressive therapy. A recent, retrospective clinical study found that administering Temozolomide in the morning increased patient overall survival by 6 months compared to evening. Previous work has shown that murine and human models of GBM have cell-intrinsic circadian rhythms in expression of the core clock genes Bmal1 and Per2. This suggests that GBM has circadian rhythms that entrain to the hosts’ central clock. Understanding the mechanisms underlying circadian entrainment and tumor growth in GBM is essential to determine whether regulation of tumor biology and susceptibility to therapies varies with time of day. Here, we tested the hypothesis that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We found that GBM cells transduced with luciferase reporters to record clock gene expression have intrinsic circadian rhythms, with Bmal1 peaking 8-12 h before Per2 in murine and human cell lines in vitro and in vivo. Further, intrinsic circadian rhythms in clock gene expression in GBM entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We found daily glucocorticoids (i.e., Dexamethasone) promoted or suppressed GBM growth depending on time of day of administration and on the clock gene, Bmal1. Blocking circadian signals, like VIP or glucocorticoids, dramatically slowed GBM growth and disease progression. Our results suggest that GBM tumors entrain to the circadian circuit of the brain and depend on clock-controlled cues like VIP and glucocorticoids to grow at specific times of day. This work may inform personalized circadian medicine to improve individual GBM patient outcomes.
CNSC-30. DETERMINING THE REGULATION AND FUNCTION OF ANGPT1 HIGH-GRADE GLIOMAS
Authors: Langhnoja Jaldeep , Wei Xin , Arounleut Phonepasong , Kundu Ipsita , Phoenix Timothy 
Published: November 2024

Abstract
Angiopoietin-1 (Angpt1) is a secreted protein that promotes angiogenesis and vascular stability in development and certain disease states through activation of the Tie2 receptor. However, little is known about its regulation and function in brain tumors. Angpt1 is upregulated in glial brain tumors, including high-grade gliomas and ependymomas. We find Angpt1 is expressed by specific cell populations within gliomas, along with non-tumor reactive astrocytes and perivascular mural cells. Leveraging an in vivo brain tumor modeling system we have generated glioma models to investigate how tumor cell state impacts Angpt1 expression, along with creating Angpt1 knock-out models. We find that Angpt1 expression is increased when glioma models are biased towards a more astrocytic and/or mesenchymal state, mirroring developmental expression patterns. Ongoing studies utilizing these models are being used to determine the mechanisms that regulate the dynamic expression of Angpt1 and its function in glioma pathogenesis, including tumor angiogenesis and blood-brain barrier function.