Therapy enhancing chromosome instability may be advantageous for gliomas.
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| Natura: | Artículo científico |
| Lingua: | en |
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NAR cancer
2025
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| _version_ | 1868266242355232769 |
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| author | Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V |
| author_facet | Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V |
| collection | PubMed - marine biology |
| contents | Therapy enhancing chromosome instability may be advantageous for gliomas. Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V Humans Glioma Isocitrate Dehydrogenase Chromosomal Instability Brain Neoplasms Cell Line, Tumor Tumor Suppressor Protein p53 Temozolomide Paclitaxel Mutation, Missense Recently revised brain tumor classification suggested a glioma treatment strategy that takes into consideration molecular variants in and marker genes. While pathogenic variants of IDH1 and TP53 can be accompanied by chromosomal instability (CIN), the impact of and mutations on genome stability remains unstudied. Elevated CIN might provide therapeutic targets, based on synergistic effects of chemotherapy with CIN-inducing drugs. Using an assay based on human artificial chromosomes, we investigated the impact of common glioma missense mutations in and on chromosome transmission and demonstrated that IDH1R132H and TP53R248Q variants elevate CIN. We next found enhanced CIN levels and the sensitivity of and genotypes, introduced into U87 MG glioma cells by CRISPR/Cas9, to different drugs, including conventional temozolomide. It was found that U87 MG cells carrying exhibit dramatic sensitivity to paclitaxel, which was independently confirmed on cell cultures derived from patients with naturally occurring . Overall, our results suggest that the development of CIN-enhancing therapy for glioma tumors with the genotype could be advantageous for adjuvant treatment. |
| format | Artículo científico |
| id | pubmed_39949830 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | NAR cancer |
| record_format | pubmed |
| spellingShingle | Therapy enhancing chromosome instability may be advantageous for gliomas. Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V Humans Glioma Isocitrate Dehydrogenase Chromosomal Instability Brain Neoplasms Cell Line, Tumor Tumor Suppressor Protein p53 Temozolomide Paclitaxel Mutation, Missense Therapy enhancing chromosome instability may be advantageous for gliomas. Goncharov, Nikolay V Baklanov, Ivan N Gulaia, Valeriia S Shuliak, Anastasiia P Lanskikh, Daria V Zhmenia, Valeriia M Shmelev, Mikhail E Shved, Nikita A Wu, Jing Liskovykh, Mikhail Larionov, Vladimir Kouprina, Natalay Kumeiko, Vadim V Humans Glioma Isocitrate Dehydrogenase Chromosomal Instability Brain Neoplasms Cell Line, Tumor Tumor Suppressor Protein p53 Temozolomide Paclitaxel Mutation, Missense Recently revised brain tumor classification suggested a glioma treatment strategy that takes into consideration molecular variants in and marker genes. While pathogenic variants of IDH1 and TP53 can be accompanied by chromosomal instability (CIN), the impact of and mutations on genome stability remains unstudied. Elevated CIN might provide therapeutic targets, based on synergistic effects of chemotherapy with CIN-inducing drugs. Using an assay based on human artificial chromosomes, we investigated the impact of common glioma missense mutations in and on chromosome transmission and demonstrated that IDH1R132H and TP53R248Q variants elevate CIN. We next found enhanced CIN levels and the sensitivity of and genotypes, introduced into U87 MG glioma cells by CRISPR/Cas9, to different drugs, including conventional temozolomide. It was found that U87 MG cells carrying exhibit dramatic sensitivity to paclitaxel, which was independently confirmed on cell cultures derived from patients with naturally occurring . Overall, our results suggest that the development of CIN-enhancing therapy for glioma tumors with the genotype could be advantageous for adjuvant treatment. |
| title | Therapy enhancing chromosome instability may be advantageous for gliomas. |
| topic | Humans Glioma Isocitrate Dehydrogenase Chromosomal Instability Brain Neoplasms Cell Line, Tumor Tumor Suppressor Protein p53 Temozolomide Paclitaxel Mutation, Missense |
| url | https://pubmed.ncbi.nlm.nih.gov/39949830/ |