A high-glucose diet stimulates an anti-tumor immune response to glioblastoma via gut microbiota modulation
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ABSTRACT:
PROVIDER: PRJNA918575 | ENA |
REPOSITORIES: ENA
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Project description:A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supplied GL261 syngeneic glioblastoma (GBM) model mice with a short-term high-glucose diet (HGD) and found an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota by an HGD was critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing showed that modulation of the gut microbiota by an HGD increased the T cell-mediated anti-tumor immune response in GBM mice. We found that the cytotoxic CD4+ T cell population in GBM mice increased due to synergy with anti-PD-1 immune checkpoint inhibitors, but this depended on an HGD. Thus, we determined that an HGD enhanced anti-tumor immune responses in GBM mice through changes in the gut microbiota and suggest that the role of an HGD in GBM should be re-examined.
2023-09-19 | GSE222192 | GEO
Project description:Viral infection makes us feel sick. The extent of these changes to our metabolism are relative to the severity of disease. Whether blood glucose levels are subject to infection-induced modulation is largely unknown. Here we show that strong, non-lethal infection restricts systemic glucose availability which promotes the antiviral IFN-I response. Following systemic viral infection of mice, we find that IFNγ produced by γδ T cells directly stimulates pancreatic β-cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous glucose output by the liver. Glucose restriction enhances type-I interferon production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, which explains why patients with metabolic disease are more susceptible to viral infection.
2024-04-14 | GSE263599 | GEO
Project description:Viral infection makes us feel sick. The extent of these changes to our metabolism are relative to the severity of disease. Whether blood glucose levels are subject to infection-induced modulation is largely unknown. Here we show that strong, non-lethal infection restricts systemic glucose availability which promotes the antiviral IFN-I response. Following systemic viral infection of mice, we find that IFNγ produced by γδ T cells directly stimulates pancreatic β-cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous glucose output by the liver. Glucose restriction enhances type-I interferon production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, which explains why patients with metabolic disease are more susceptible to viral infection.
2024-04-14 | GSE263600 | GEO
Project description:Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression
| PRJNA544318 | ENA
Project description:This model is based on paper:
Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy
Abstract:
Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.
2024-09-02 | BIOMD0000000828 | BioModels
Project description:This model is based on paper, based on its cell cycle dynamics model:
Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy
Abstract:
Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.
2024-09-02 | BIOMD0000000829 | BioModels
Project description:Macrophages are critical components of the immunosuppressive microenvironment that restrict anti-cancer immunity in glioblastoma (GBM). However, how GBM shapes the regulatory function of macrophages remains elusive. Here, we report that monocyte-derived macrophages (MDM), but not yolk-sac derived microglia (MG), exhibited potent immunosuppressive activity, which was mediated by a population of glycolytic GLUT1+MDM, in an IL10-dependent manner. GBM-derived factors reprogrammed MDM towards glycolytic cells with enhanced avidity for glucose, which was mostly used to generate lactate. In turn, intracellular lactate caused lactylation of histone lysine residues that promoted MDM immunosuppressive activity via regulation of Il10 expression. GBM-primed activation of PERK supported glucose metabolism and regulated GLUT1 expression through ATF4 in MDM. PERK-deletion in MDM abrogated histone lactylation and suppressive activity, thereby promoting polyfunctional T cell-infiltration of tumors. In combination with immunotherapy, PERK-deletion blocked GBM progression. Our study demonstrates that glucose-driven histone lactylation controls MDM immunosuppressive function; all in a PERK-dependent manner.
2024-05-06 | GSE260700 | GEO
Project description:MicroRNAs are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules can represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme (GBM), the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly upregulated in glioblastoma and a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, miR-181c, which are down-regulated in glioblastoma.
2005-09-23 | E-TABM-37 | biostudies-arrayexpress
Project description:Glioblastoma, the most aggressive primary brain cancer, has dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we here systematically screen repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform. Profiling >2,500 ex vivo drug responses across 27 patients and 132 drugs identified class-diverse neuroactive drugs with potent anti-glioblastoma efficacy that were validated across model systems. Interpretable molecular machine learning of drug-target networks revealed neuroactive convergence on AP-1/BTG-driven glioblastoma suppression, enabling expanded in silico screening of >1 million compounds with high patient validation accuracy. Deep multi-modal profiling confirmed Ca2+-driven AP-1/BTG-pathway induction as a neuro-oncological glioblastoma vulnerability, epitomized by the antidepressant Vortioxetine synergizing with current standard-of-care chemotherapies in vivo. These findings establish an actionable framework for glioblastoma treatment rooted in its neural etiology.
| MSV000090357 | MassIVE
Project description:Animals with intracranial glioblastoma of the NS1 cells line were treated with anti-C1-INH +/- radiotherapy or were untreated control animals.
2022-10-19 | E-MTAB-12296 | biostudies-arrayexpress