CNS Tumor

In our patient, the sarcomatous component exhibited p53 and OLIG2 immunohistochemical expression. Molecular analysis revealed IDH and TERT mutations, as well as 1p/19q and CDKN2A deletions.

Our findings confirm that glioblastoma tissues can be categorized into glycolytic-dominant and mitochondrial-dominant types, as previously reported. The mitochondrial-dominant type is also glutaminolysis-dominant. Therefore, inhibiting the glutaminolysis pathway may be an effective treatment for mitochondrial-dominant glioblastoma.

Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.

The SaCas9-KKH induced a genomic deletion, resulting in lowered mmu-miR-21a levels in the brain, leading to reduced tumor growth and improved overall survival. In this study, we demonstrated that disruption of genomic mmu-miR-21a with a single AAV vector influenced glioma development resulting in beneficial anti-tumor outcomes in GB-bearing mice.

Functional validation in patient-derived glioma stem cells and animal models highlights nucleotide metabolism as a promising therapy target for gliomas. This integrated multi-omics analysis introduces a proteomic classification for gliomas and identifies DPYD and TYMP as key metabolic biomarkers, offering insights into glioma pathogenesis and potential treatment strategies.

P2, N=60, Not yet recruiting, Massachusetts General Hospital | N=40 --> 60

P1, N=68, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2027 --> Feb 2028 | Trial primary completion date: Oct 2024 --> Feb 2025

P=N/A, N=60, Active, not recruiting, Maastricht Radiation Oncology | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=60, Not yet recruiting, Tata Memorial Centre | Initiation date: Aug 2024 --> Jan 2025

High levels of HIF-1α expression were associated with poorer survival outcomes and other clinicopathological characteristics of glioblastoma. Integrating HIF-1α into prognostic tools for glioblastoma aids in predicting survival, categorising risk, and advising patients on suitable treatment regimens.

B7-H3 nanoCAR-T cells showed promise for glioblastoma therapy following in vitro characterization, but limiting in vivo toxicity was observed. Off-tumor recognition of healthy mouse tissue by the cross-reactive B7-H3 nanoCAR-T cells was identified as a potential cause for this toxicity, warranting caution when using highly sensitive nanoCAR-T cells, recognizing the low-level expression of B7-H3 on healthy tissue.

In conclusion, our data show that C1GALT1 enhances the progression of glioma by regulated the O-glycosylation and phosphorylation of EGFR and the subsequent downstream AKT/ERK signaling pathway. Therefore, C1GALT1 represents a potential target for the diagnosis and treatment of glioma.

The MiCBO-TF model represents a powerful platform for both mechanistic investigations and the development of precision medicine approaches for DMG.

To lay the groundwork for the future rational optimization of this promising class of compounds, the molecular bases of DM1 and DM2 activity were investigated by modelling their interaction with hCav3.1 channels. The calculated binding modes of DM1 and DM2 to hCav3.1 channels partially mirrored that of the selective Cav3.1 blocker Z944, paving the way for future lead optimization.

Silencing RPS3A inhibited autophagy in U251 cells, whereas rapamycin, an activator of autophagy, reversed the inhibitory effect of RPS3A silencing on TAM M2 polarization...Overexpression of CSF1 promoted the proliferation and invasion of U251 cells and reversed the inhibitory effect of RPS3A silencing on TAM proliferation and invasion, but had no effect on TAM M2 polarization. The results of in vivo experiments showed that knockdown of RPS3A significantly inhibited glioma tumor growth and metastasis in vivo. This study revealed that RPS3A recruited TAMs by upregulating E4F1-mediated transcription activation of CSF1, and promoted the M2 polarization of TAMs through autophagy, promoting glioma cell malignant growth and tumor progression.

Mechanistic studies revealed that among active compounds, amide-type harmicens 12 and 14 inhibit DYRK1A and Hsp90 CTD, whereas compound 14 showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions.

Rapid central pathology review and molecular testing for eligibility was feasible. The protocol therapy including radiation, veliparib and temozolomide was well tolerated but failed to improve outcome compared to clinically and molecularly matched historical control cohorts treated with higher doses of alkylator chemotherapy.

Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

This case highlights the importance of comprehensive genetic testing in patients with pheochromocytoma and paraganglioma, particularly when hereditary syndromes are suspected. Genetic insights ensure precise management, allowing for tailored treatment and improved outcomes in patients with hereditary pheochromocytoma and paraganglioma.

Six characteristic genes (BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM) were identified by machine learning, and these genes are associated with multiple immune-related pathways and immune cells in neuroblastoma. BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM may serve as biomarkers that reflect the conditions of the immune microenvironment of neuroblastoma and hold promise in guiding neuroblastoma treatment.

At present, the crystal complex structure of SHP099 with SHP2-E76K has been reported in the RCSB PDB protein data bank, however, the dynamic structure of SHP099 binding to the active center of SHP2-E76K protein was still lacking. Therefore, this study used molecular dynamics simulation and Markov model to characterize the kinetics of the inhibitor SHP099 with SHP2-E76K enzyme and to determine the active binding site, which would give a hint of a vital enzyme-substrate interaction in atomistic detail that proposed the potential to be applied for the discovery of more effective SHP2-E76K inhibitors and, in broader terms, dynamic protein-drug interactions.

Here, we show that the IRDS signature, linked to chemo-resistance in other cancers, can be induced in glioblastoma by microglia. ISG genes and the microglia inducing the ISG expression could be promising novel therapeutic targets in glioblastoma.

In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases.

CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.

These findings provide a new perspective on the critical role of the noradrenergic system in mediating mirtazapine's effects on BDNF translation. We propose a novel mechanism of action in which mirtazapine promotes norepinephrine release and noradrenergic responses by upregulating ADRA2A and ADRB2 while downregulating serotonergic receptors.

This study demonstrates that integrating clinical and radiotherapy-derived AI-driven phenotypes can predict MGMT methylation. The framework addresses constraints that limit molecular diagnosis access.

Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole-induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.

P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31

P1, N=21, Active, not recruiting, University of Florida | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=134, Recruiting, Academic and Community Cancer Research United | Not yet recruiting --> Recruiting

P3, N=200, Not yet recruiting, Vastra Gotaland Region | Initiation date: May 2024 --> Dec 2024

Young adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long-term outcomes in ANNA1 autoimmunity.

P1, N=59, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

The study also highlights the plausible role of pyrethroids to be implicated in the deleterious effects of pesticides in a mixture. To the best of our knowledge, our finding is the first in toxicoproteomics to deeply elucidate pesticides' molecular interactions and their ability to adduct proteins as a pivotal role in the neurotoxicity mechanism.

Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX.

P2, N=262, Completed, Children's Oncology Group | Active, not recruiting --> Completed

To the best of our knowledge, this study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.

NKTR-255, a polymer-conjugated recombinant human interleukin-15 agonist, significantly stimulated NK cell proliferation and expansion and further enhanced the in vitro cytotoxic activity and in vivo anti-tumor efficacy of anti-MCAM-CAR-NK cells against NB. Our preclinical studies demonstrate that ex vivo expanded and modified anti-MCAM-CAR-NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAMhigh malignant NB.

Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression. These findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.

ALDH1A1 is a primary metabolic enzyme impacting the outcome of chemotherapy, including temozolomide...Evidence from a nationwide cancer registry has suggested PPIs have a negative impact on OS for GBM patients, particularly those with MGMT promoter methylation. This suggests PPIs should be avoided for prophylactic management of gastrointestinal toxicity in patients with GBM receiving chemoradiotherapy.

This study shows that the incorporation of molecular testing can considerably improve brain tumor diagnoses in Nigeria. Furthermore, this study highlights the diagnostic challenges in resource-limited settings and what is at stake in the global disparities of brain tumor diagnosis.

In recent years, it has been shown that dysregulation of molecular mechanisms in many LncRNAs such as MIR22HG, HULC, AGAP2-AS1, MALAT1, PVT1, TTTY14, HOTAIRM1, PTAR, LPP-AS2, LINC00336, and TINCR are connected with the GBM. Therefore, this scientific review paper focused on the molecular mechanisms of these LncRNAs in the context of GBM.