Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma DOI Creative Commons
Bin Liao, Pan Wang,

Sheng Gong

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Background This study investigates whether Hypoxia-Inducible Factor 1 alpha (HIF1α) and 2 (HIF2α) coordinately regulate insulin-like growth factor receptor (IGF1R) expression, thereby influencing chemosensitivity in glioblastoma multiforme (GBM). Methods We analyzed the expression correlation of HIF1α, HIF2α, IGF1R glioma using The Cancer Genome Atlas (TCGA) Chinese Glioma (CGGA) databases. Immunohistochemistry (IHC) was performed to detect GBM tissues cells, as well oxygen tension. Cell cycle analysis, apoptosis assays, lactate dehydrogenase (LDH) release measurements, Western blotting, xenograft tumor models were employed explore synergistic regulation by HIF1α focusing on activation PI3K/AKT signaling pathway its contribution drug resistance. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) dual-luciferase reporter assays used investigate binding sites HIF2α involved regulating IGF1R. Results Our demonstrated that highly expressed hypoxia-cultured their positively correlated with expression. Simultaneous knockout cells resulted highest LDH rates under hypoxic conditions, accompanied most significant decrease IGF1R, p-PDK1, p-AKT levels. Knockout hypoxia led an increas rates, reduced phosphorylation PDK1 AKT. In addition, we promoted a specific response element (HRE) sequence (5′-GAACGTGCCT-3′) within promoter system. Conclusion Glioblastoma residing microenvironment, exhibit high HIF2α. These transcription factors promote upregulation which subsequently activates pathway. activation, turn, promotes cell proliferation chemoresistance, ultimately contributing malignancy.

Language: Английский

Glioblastoma Cell Migration, Invasion and Vasculogenic Mimicry Downmodulated by Novel uPAcyclin Derivatives DOI Creative Commons
F Santoro, Francesco Merlino, Diego Brancaccio

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 259 - 259

Published: Feb. 12, 2025

Despite extensive efforts to develop new treatments, the prognosis for glioblastoma multiforme (GBM) is extremely unfavorable, urging identification of chemotherapeutics. A previous work identified cyclic decapeptide uPAcyclin as a potent inhibitor GBM cell migration, matrix invasion and vascular-like structures' formation, acting through binding αV integrins not interfering with proliferation or survival. These clearcut activities prompted us design test novel derivatives on cultured U87-MG U251 GBM-MG human cells. With exception residues involved in peptide cyclization, were Ala-substituted one by single peptides tested affinity target integrin, inhibition vasculogenic mimicry. The first screening highlighted low inhibitory ability (Ala4,7,9 derivatives) capacity higher than (Ala2,5,6,8 derivatives). integration these results conformational studies led di-substituted variant uPAcyclin. Intriguingly, at least ten-fold greater anti-migratory anti-invasive effects [Ala2,Ala5]uPAcyclin compared found. latter also exhibited potential formation matrix-seeded shed light functional relevance amino acid lead therapeutically interesting variants promising candidates anti-GBM therapies.

Language: Английский

Citations

1
Comparative Clinical-Imaging and Histogenetic Analysis Between Astrocytoma IDH-Mutant Grade 4 and Glioblastoma IDH-Wildtype—Is There Really a Worse One? DOI Creative Commons
Cristian Ionuț Orășanu, Mariana Aşchie, Mariana Deacu

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(4), P. 438 - 438

Published: Feb. 11, 2025

Background: Brain tumors pose a significant health threat, leading to high morbidity and mortality rates. Astrocytoma IDH-mutant grade 4 (A4IDHmt) glioblastoma IDH-wildtype (G4IDHwt) exhibit similar clinical imaging characteristics. This study aims highlight the differences in their evolution histogenetic aspects with possible therapeutic impact, as well adverse prognostic factors patient survival. Methods: We performed 10-year retrospective of gliomas, evaluating immunomarkers FISH tests. also quantified tumor necrosis microvascular density. Results: A total 81 cases were identified; 54.32% A4IDHmt. observed that A4IDHmt patients younger (34.10% under 50) had higher survival rate (4.55%). group exhibited more pronounced density (p = 0.010) proliferative index 0.026). G4IDHwt was associated larger volumes (94.84 cm3 vs. 86.14 cm3), lower resectability rates (82.88% 87.67%), immature cell population (83.78% 68.18%). In case both, negative risk on univariate analysis is given by advanced age (A4IDHmt: HR 1.035, G4IDHwt: 1.045) p53 immunopositivity 6.962, 4.680). Conclusions: The for include rapid onset symptoms (HR 2.038), diabetes mellitus 2.311), arterial hypertension 2.325), residual 2.662), increased volume 1.060), 1.096), 1.097). For G4IDHwt, consist 1.023), lost PTEN immunoreaction 33.133), unmethylated DNA status 6.765, respectively 20.573). Even if it has factors, lesser evil.

Language: Английский

Citations

0
Targeting EGFR and PI3K/mTOR pathways in glioblastoma: innovative therapeutic approaches DOI

Gursimran Singh,

Rohit Rohit,

Pankaj Kumar

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 10, 2025

Language: Английский

Citations

0
Potential of Curcumin and Its Analogs in Glioblastoma Therapy DOI Creative Commons
Agnieszka Nowacka, Ewa Ziółkowska, Wojciech Smuczyński

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 351 - 351

Published: March 18, 2025

Curcumin, a polyphenol found in turmeric, demonstrates multifaceted anti-cancer activity against glioblastoma. Its therapeutic potential stems from its ability to modulate various molecular pathways implicated glioblastoma development and progression, enhance the effectiveness of radiation therapy, induce cancer cell death through diverse mechanisms, including apoptosis, autophagy, cycle arrest. These combined actions make curcumin promising candidate for treatment, warranting further investigation into clinical application. In this review, we summarize latest research on analogs' therapy.

Language: Английский

Citations

0
Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma DOI Creative Commons
Bin Liao, Pan Wang,

Sheng Gong

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Background This study investigates whether Hypoxia-Inducible Factor 1 alpha (HIF1α) and 2 (HIF2α) coordinately regulate insulin-like growth factor receptor (IGF1R) expression, thereby influencing chemosensitivity in glioblastoma multiforme (GBM). Methods We analyzed the expression correlation of HIF1α, HIF2α, IGF1R glioma using The Cancer Genome Atlas (TCGA) Chinese Glioma (CGGA) databases. Immunohistochemistry (IHC) was performed to detect GBM tissues cells, as well oxygen tension. Cell cycle analysis, apoptosis assays, lactate dehydrogenase (LDH) release measurements, Western blotting, xenograft tumor models were employed explore synergistic regulation by HIF1α focusing on activation PI3K/AKT signaling pathway its contribution drug resistance. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) dual-luciferase reporter assays used investigate binding sites HIF2α involved regulating IGF1R. Results Our demonstrated that highly expressed hypoxia-cultured their positively correlated with expression. Simultaneous knockout cells resulted highest LDH rates under hypoxic conditions, accompanied most significant decrease IGF1R, p-PDK1, p-AKT levels. Knockout hypoxia led an increas rates, reduced phosphorylation PDK1 AKT. In addition, we promoted a specific response element (HRE) sequence (5′-GAACGTGCCT-3′) within promoter system. Conclusion Glioblastoma residing microenvironment, exhibit high HIF2α. These transcription factors promote upregulation which subsequently activates pathway. activation, turn, promotes cell proliferation chemoresistance, ultimately contributing malignancy.

Language: Английский

Citations

0