Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 133 - 133

Published: Jan. 8, 2025

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy chemotherapy. Sesquiterpene triterpenoids (STLs) their semi-synthetic analogs are considered as a promising source novel anti-tumor agents due low systemic toxicity multi-target pharmacological effects on key processes associated with tumor progression. The current review aims systematize knowledge anti-glioblastoma potential STLs accumulated over last decade identify in glioblastoma cells that susceptible action STLs. An analysis published data clearly demonstrated STLs, which can successfully cross blood-brain barrier, exert complex inhibitory effect through induction "mitochondrial dysfunction-oxidative stress-apoptosis" axis, inhibition glucose metabolism cell cycle phase transition, suppression motility invasion blockade proneural-mesenchymal transition. Taken together, this highlights not only able induce death, but also effectively affect diffusive spread, suggests possible directions for further investigation context better understand mechanism action.

Language: Английский

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Advancing Glioblastoma Therapy: Learning From the Past and Innovations for the Future

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217601 - 217601

Published: March 1, 2025

Language: Английский

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The Role of Gut Microbiome on Glioblastoma Oncogenesis and Malignant Evolution

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2935 - 2935

Published: March 24, 2025

Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy temozolomide, radiotherapy. While immunotherapy targeted treatments show promise, therapeutic resistance disease progression remain major challenges. This is partly due GBM's classification as a "cold tumor" low mutational burden lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights gut microbiota key player in cancer biology, influencing both glioma development response. review explores intersectionality between microbiome GBM, beginning an overview composition its broader implications pathophysiology. We then examine how specific microbial populations contribute oncogenesis, modulating immune responses, inflammation, metabolic pathways drive tumor initiation progression. Additionally, we discuss microbiome's role resistance, including impact on chemotherapy, radiotherapy, efficacy. Given influence outcomes, evaluate emerging strategies modulate flora, such probiotics, dietary interventions, microbiota-based therapeutics, enhance therapy response GBM patients. Finally, address challenges future directions, emphasizing need standardized methodologies, mechanistic studies, clinical trials validate microbiota-targeted interventions neuro-oncology. By integrating research into paradigms, may unlock novel avenues improve patient outcomes.

Language: Английский

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Pentraxin 3: A Main Driver of Inflammation and Immune System Dysfunction in the Tumor Microenvironment of Glioblastoma

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1637 - 1637

Published: April 24, 2024

Brain tumors are a heterogeneous group of brain neoplasms that highly prevalent in individuals all ages worldwide. Within this pathological framework, the most and aggressive type primary tumor is glioblastoma (GB), subtype glioma falls within IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring few months after diagnosis, even gold-standard therapies now available, such as surgery, radiation, or pharmaceutical approach Temozolomide. For reason, it crucial to continue looking cutting-edge therapeutic options raise patients’ survival chances. Pentraxin 3 (PTX3) multifunctional protein has variety regulatory roles inflammatory processes related extracellular matrix (ECM). An increase PTX3 blood levels considered trustworthy factor associated beginning inflammation. Moreover, scientific evidence suggested sensitive earlier inflammation-related marker compared short pentraxin C-reactive (CRP). In several tumoral subtypes, via regulating complement-dependent macrophage-associated tumor-promoting inflammation, been demonstrated may function promoter cancer metastasis, invasion, stemness. Our review aims deeply evaluate context GB, considering its pivotal biological activities possible role molecular target future therapies.

Language: Английский

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Nanotherapeutic strategy against glioblastoma using enzyme inhibitors

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117713 - 117713

Published: Nov. 29, 2024

Language: Английский

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COSMC-Regulated O-Glycosylation: A Bioinformatics-Driven Biomarker Identification for Stratifying Glioblastoma Stem Cell Subtypes

Kinases and Phosphatases, Journal Year: 2024, Volume and Issue: 2(4), P. 391 - 412

Published: Dec. 22, 2024

Glioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability diversity, which make them challenging target effectively. This study explores the O-glycosylation differentiating two GSC subtypes, CD133 CD44. We utilized TCGA dataset GBM presented reproducible bioinformatics analysis for our results. Our profiling showed enriched signatures CD44-expressing over CD133, with Cosmc, chaperone core mucin-type O-glycosylation, significantly upregulated CD44-positive group. Moreover, Cosmc was associated shorter progression-free intervals, suggesting its potential as an indicator aggressive disease. High expression also immune-related pathways, including inflammatory response antigen presentation, presence myeloid cells, T NK cells. Additionally, elevated correlated extracellular matrix (ECM) pathways stromal cell populations, such perivascular fibroblasts. These findings position specially, a promising biomarker distinguishing subclones, relevance immune modulation, ECM dynamics, identifying it novel therapies.

Language: Английский

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Combined use of radiomics and artificial neural networks for the three‐dimensional automatic segmentation of glioblastoma multiforme

Expert Systems, Journal Year: 2024, Volume and Issue: unknown

Published: April 14, 2024

Abstract Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumour that has worst prognosis in adults. Currently, automatic segmentation of this kind being intensively studied. Here, three‐dimensional GBM achieved with its related subzones (active tumour, inner necrosis, peripheral oedema). Preliminary segmentations were first defined based on four basic magnetic resonance imaging modalities classic image processing methods (multithreshold Otsu, Chan–Vese active contours, morphological erosion). After an gap‐filling post step, these preliminary combined corrected by a supervised artificial neural network multilayer perceptron type hidden layer 80 neurons, fed 30 selected radiomic features gray intensity texture. Network classification overall accuracy 83.9%, while complete algorithm achieves average Dice similarity coefficients 89.3%, 80.7%, 79.7%, 66.4% for entire region interest, oedema, necrosis segmentations, respectively. These values are range best reported present bibliography, but even better Hausdorff distances lower computational costs. Results presented here evidence it possible to achieve traditional radiomics. This relevant clinical potential at time diagnosis, precision radiotherapy planning, or post‐treatment response evaluation.

Language: Английский

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Glioma Stem Cells: GPRC5A as a Novel Predictive Biomarker and Therapeutic Target Associated with Mesenchymal and Stemness Features

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(18), P. 8482 - 8482

Published: Sept. 20, 2024

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite understanding GBM biology, remains highly resistant to any therapy. Therefore, defining innovative biomarkers in can provide insights into tumor biology and potential therapeutic targets. In this study, we explored GPRC5A serve as a pertinent biomarker for GBM. We utilized GBM-TCGA dataset presented reproducible bioinformatics analysis our results. identified that expression was significantly upregulated compared normal tissues, with higher levels correlating poor overall survival (OS) progression-free interval (PFI). Moreover, it associated key genetic mutations, particularly NF1 PTEN strongly correlated mesenchymal stem-like phenotype. also predominantly aggressive features, including hypoxia, high extracellular matrix (ECM) environments, extensive stromal immune infiltrations. Its strong correlation markers hypoxic regions underscores target These findings valuable role pathology impact stratifications treatment strategies.

Language: Английский

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A Comprehensive review on exploring Thymoquinone as novel therapeutic molecule for clinical management of Glioblastoma Multiforme

Pharmacological Research - Natural Products, Journal Year: 2024, Volume and Issue: unknown, P. 100107 - 100107

Published: Oct. 1, 2024

Language: Английский

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Contemporary strategies in glioblastoma therapy: Recent developments and innovations

Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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