Der Nervenarzt, Journal Year: 2023, Volume and Issue: 95(2), P. 96 - 103
Published: Dec. 29, 2023
Neuro-Oncology Advances, Journal Year: 2023, Volume and Issue: 5(1)
Published: Jan. 1, 2023
Glioblastoma (GBM) tumor microenvironment (TME) is a highly heterogeneous and complex system, which in addition to cancer cells, consists of various resident brain immune cells as well transit through the such marrow-derived cells. The TME dynamic environment heavily influenced by alterations cellular composition, cell-to-cell contact metabolic products other chemical factors, pH oxygen levels. Emerging evidence suggests that GBM appear reprogram their TME, hijack microenvironmental elements facilitate rapid proliferation, invasion, migration, survival thus generating treatment resistance. interact with directly interaction mediated cell-surface molecules, or indirectly apocrine paracrine signaling via cytokines, growth extracellular vehicles. recent discovery neuron-glioma interfaces neurotransmitter-based interactions has uncovered novel mechanisms favor cell growth. Here, we review known emerging related communication between components its discuss models for studying outline current studies targeting therapeutic purposes.
Language: Английский
Citations
146
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2563 - 2563
Published: Feb. 22, 2024
Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding tissue. While lower-grade gliomas present more circumscribed borders, high-grade aggressive with widespread infiltration and dissemination. Glioblastoma (GBM) known for its high invasiveness association poor prognosis. Its low survival rate due to certainty recurrence, caused microscopic which makes surgical eradication unattainable. New insights GBM biology at single-cell level have enabled identification mechanisms exploited glioma cells invasion. In this review, we explore current understanding several molecular pathways used tumor invade normal We address intrinsic biological drivers cell invasion, tackling how interact each other microenvironment (TME). focus on recently discovered neuronal niche in TME, including local as well distant neurons, contributing growth then promoted astrocytes immune cells. Finally, review literature therapeutic targeting
Language: Английский
Citations
15
Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 682 - 682
Published: April 15, 2024
The tumor microenvironment (TME) plays an important role in the process of tumorigenesis, regulating growth, metabolism, proliferation, and invasion cancer cells, as well contributing to resistance conventional chemoradiotherapies. Several types cells with relatively stable phenotypes have been identified within TME, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils, natural killer (NK) which shown modulate cell metastasis, interaction immune system, thus promoting heterogeneity. Growing evidence suggests that tumor-cell-derived extracellular vesicles (EVs), via transfer various molecules (e.g., RNA, proteins, peptides, lipids), play a pivotal transformation normal TME into their protumorigenic counterparts. This review article focuses on functions EVs modulation view how exosomes contribute importance for diagnosis therapy.
Language: Английский
Citations
9
JCI Insight, Journal Year: 2024, Volume and Issue: 9(1)
Published: Jan. 8, 2024
Epilepsy has a profound impact on quality of life. Despite the development new antiseizure medications (ASMs), approximately one-third affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human animal model studies implicated immunotherapeutic metabolomic approaches that may benefit with epilepsy. In this Review, we detail proinflammatory immune landscape contrast immunosuppressive microenvironment in glioma-related tumor setting, excessive facilitates immunosuppression, thereby contributing subsequent glioma progression. Metabolic modulation IDH1-mutant pathway provides dual for reversing suppression dampening seizure activity. Elucidating relationship between neurons immunoreactivity is an area prioritization next era ASMs.
Language: Английский
Citations
8
Molecular Oncology, Journal Year: 2024, Volume and Issue: unknown
Published: April 3, 2024
In recent years, the discovery of functional and communicative cellular tumour networks has led to a new understanding malignant primary brain tumours. this review, authors shed light on diverse nature cell‐to‐cell connections in tumours propose an innovative treatment approach address detrimental connectivity these networks. The proposed therapeutic outlook revolves around three main strategies: (a) supramarginal resection removing substantial portion communicating cell front far beyond gadolinium‐enhancing mass, (b) morphological isolation at single level disrupting structural contacts facilitated by elongated membrane protrusions known as microtubes (TMs), (c) blocking TM‐mediated intercellular cytosolic exchange inhibiting neuronal excitatory input into network. We draw analogy between Alcatraz Federal Penitentiary, where inmates faced impassable sea barrier experienced both spatial within individual cells. Based current translational efforts ongoing clinical trials, we Alcatraz‐Strategy promising framework tackle harmful effects
Language: Английский
Citations
7
British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(8), P. 1327 - 1338
Published: Aug. 24, 2023
Abstract Background Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of situ microenvironment affects clinically-predictive value this model. We implemented a GSC monolayer system investigate - vitro molecular correspondence and relationship between patient response temozolomide (TMZ). Methods DNA/RNA-sequencing was performed on 56 glioblastoma tissues 19 derived cultures. Sensitivity TMZ screened across 66 Viability readouts were related clinical parameters corresponding patients whole-transcriptome data. Results Tumour DNA RNA sequences revealed strong similarity GSCs despite neuronal immune interactions. In screening yielded three categories which significantly correlated with survival, therewith providing more specific prediction than binary MGMT marker. Transcriptome analysis identified 121 genes sensitivity 21were validated external datasets. Conclusion retain patient-unique hallmark gene expressions their natural environment. Drug using predicted specifically status, while transcriptome potential biomarkers for response. drug therefore provides tool improve development precision medicine glioblastoma.
Language: Английский
Citations
14
Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1042 - 1042
Published: Feb. 7, 2023
Gliomas are the most frequent central nervous system (CNS) primary tumors. The prognosis and clinical outcomes of these malignancies strongly diverge according to their molecular alterations range from a few months decades. tumor-associated microenvironment involves all cells connective tissues surrounding tumor cells. composition as well interactions with associated neoplastic mass, both variables assuming an increasing interest in last years. This is mainly because can mediate progression, invasion, dedifferentiation, resistance treatment, relapse gliomas. In particular, diverges isocitrate dehydrogenase (IDH) mutated wild-type (wt) Indeed, IDH gliomas often show lower infiltration immune reduced angiogenesis compared wt On other hand, tumors exhibit strong mediated by several cytokines chemokines, including CCL2, CCL7, GDNF, CSF-1, GM-CSF, etc. presence factors, Sox2, Oct4, PD-L1, FAS-L, TGF β2, also switch toward regulatory inhibited system. Other important described between glioblastoma astrocytes, neurons, stem cells, while less elucidated IDH-mutated possibility targeting intriguing perspective terms therapeutic drug development. this review, we summarized available evidence related glioma microenvironment, focusing on differences within different subtypes possible
Language: Английский
Citations
10
Cancer Discovery, Journal Year: 2025, Volume and Issue: 15(1), P. 39 - 51
Published: Jan. 13, 2025
Abstract Deepening our understanding of neuro-cancer interactions can innovate brain tumor treatment. This mini review unfolds the most relevant and recent insights into neural mechanisms contributing to initiation, progression, resistance, including synaptic connections between neurons cancer cells, paracrine signaling, cells’ intrinsic properties. We explain basic clinical–translational relevance these findings, identify unresolved questions particularly interesting future research avenues, such as central nervous system neuro-immunooncology, discuss potential transferability extracranial cancers. Lastly, we conceptualize ways toward clinical trials develop a roadmap neuroscience-instructed therapies. Significance: Neural influences on tumors drive their growth invasion. Herein, use fundamentally new biology for improved outcomes.
Language: Английский
Citations
0
Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 23, 2025
Abstract Glioblastoma multiforme is the most devastating brain tumor without cure. Although in vitro and vivo research on glioblastoma have demonstrated its complexity, including interactions with cells microenvironment, 3D models resembling those key features allowing to study therapeutic interventions of this aggressive are scarce. Here, a model developed that establishes microenvironment hyaluronic acid‐based hydrogel cross‐linked laminin, both which components brain's extracellular matrix. This mimics mechanical properties matrix at macroscopic mesoscopic levels, as evaluated by stiffness, viscosity using rheological nanoindentation measurements. The ultra‐soft storage modulus 100 Pa reinforced printed microfiber scaffolds allow setup multicellular primary cortical neurons astrocytes cells. Tumor characterized through confocal shadow imaging disease entities functional surrounding tumor's hijacking capability neuronal signaling promote own proliferation.
Language: Английский
Citations
0
Brain and Spine, Journal Year: 2025, Volume and Issue: 5, P. 104202 - 104202
Published: Jan. 1, 2025
Functional coupling of the tumor to extralesional brain areas and pretherapeutic cognitive performance status have each independently been identified as prognostically relevant in glioma patients. It is however unclear, whether tumor-connectivity correlates with or outcome. To investigate potential associations between pre- postoperative resting-state fMRI connectivity (FC) functions patients compared healthy controls. 18 age-matched, controls underwent neuropsychological testing 4.5 months (mean) postoperatively. FC (Tu-EL) was determined, well (EL) contralesional hemisphere (conEL). Groups were regard behavioral measures. Patients showed deficits all domains tested. While tended be worse, deterioration not statistically significant timepoints. EL did differ groups, but conEL (p < .045) increased Tu-EL significantly associated worse attention .001), and, by trend .058), attentional outcome Intrinsic functional rest might relate pathological tumor-neuron interaction on macroscale, reflecting invasive nature diffusely infiltrating glioma. Deepening our understanding measures at connectomic level context cancer neuroscience may aid identifying neurophysiological impairment prognosticating
Language: Английский
Citations
0