Novel Acetamide-Based HO-1 Inhibitor Counteracts Glioblastoma Progression by Interfering with the Hypoxic–Angiogenic Pathway

D’Amico, Agata Grazia; Maugeri, Grazia; Vanella, Luca; Consoli, Valeria; Sorrenti, Valeria; Bruno, Francesca; Federico, Concetta; Fallica, Antonino Nicolò; Pittalà, Valeria; D’Agata, Velia

doi:10.3390/ijms25105389

Cited by 2 publications

References 78 publications

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TMEM35B as a novel biomarker for diagnosing gliomas

Liang,

Lai,

Yan

et al. 2024

Biomarkers in Medicine

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Aims There is little information about transmembrane protein 35B (TMEM35B) expression in glioma, and its functions in glioma remains no clue. Patients & Methods Immunohistochemistry was used to measure TMEM35B expression levels and CCK8 and Transwell assays were analyzed the proliferative and migratory and invasive. Results TMEM35B protein was significantly higher in gliomas and correlated with a higher tumor TNM stages. Receiver operating characteristic curve analysis revealed that TMEM35B had high diagnostic value in distinguishing among glioma, normal tissues, tumor stages III+IV, and I+II. Additionally, TMEM35B knockdown inhibited the proliferative, migratory, and invasive capacities of glioma cells. Conclusions TMEM35B expression is upregulated in gliomas, and its knockdown hinders tumor progression, highlighting the protein as a potential biomarker for glioma diagnosis.

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TMEM35B as a novel biomarker for diagnosing gliomas

Liang,

Lai,

Yan

et al. 2024

Biomarkers in Medicine

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Repurposing Ivermectin and ATRA as Potential Therapeutics for Glioblastoma Multiforme

Sayad,

Hiatt,

Mustafa

2024

Preprint

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BackgroundGlioblastoma multiforme (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by rapid growth and resistance to conventional therapies. Despite advances in treatment, most patients succumb to the disease within 15 months. Drug repurposing, which involves finding new uses for existing drugs, is a promising strategy to develop new GBM treatments faster and more cost-effectively.MethodWe obtained single-cell RNA sequencing (scRNA-seq) data (GSE84465) from the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) repository to compare gene expression in GBM neoplastic cells and non-neoplastic cells. We identified genes that were abnormally expressed in tumor cells and linked these genes to potential drug targets. To identify potential repurposed drugs for GBM, we leveraged the Chemical Entities of Biological Interest (ChEBI) database to assess the interaction of various compounds with the differentially expressed genes identified in the scRNA-seq analysis. We focused on compounds that could reverse the aberrant gene expression observed in GBM neoplastic cells.ResultsOur analysis suggests that ivermectin and all-trans-retinoic acid (ATRA) could be repurposed as effective treatments for GBM. Ivermectin, typically used as an antiparasitic, demonstrated strong anti-tumor activity by downregulating 40 of the top 100 upregulated genes in GBM, indicating its potential to suppress tumor growth. ATRA, known for promoting cell differentiation, upregulated 60 genes typically downregulated in GBM neoplastic cells, showing its potential to correct transcriptional dysregulation and support tumor suppression. These findings underscore the promise of drug repurposing to target key pathways in GBM, offering new therapeutic options for this aggressive cancer.ConclusionsOur results provide compelling evidence that ivermectin and ATRA may be effective in treating GBM. The observed alterations in gene expression indicate the ability of these two agents to disrupt key genes and pathways crucial for tumor progression. Given the increasing interest in drug repurposing for cancer treatment, comprehensive preclinical and clinical investigations are warranted to assess fully the therapeutic efficacy of these compounds against this disease.

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Novel Acetamide-Based HO-1 Inhibitor Counteracts Glioblastoma Progression by Interfering with the Hypoxic–Angiogenic Pathway

Cited by 2 publications

References 78 publications

TMEM35B as a novel biomarker for diagnosing gliomas

TMEM35B as a novel biomarker for diagnosing gliomas

Repurposing Ivermectin and ATRA as Potential Therapeutics for Glioblastoma Multiforme

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