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Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor

Brain tumors have been proved challenging to treat. Here we established a Multi-Target Neural Differentiation (MTND) therapeutic cocktail to achieve effective and safe treatment of brain malignancies by targeting the important hallmarks in brain cancers: poor cell differentiation and compromised cel...

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Detalles Bibliográficos
Autores principales: Hu, Xiaoping, Xie, Jingdun, Yang, Yilin, Qiu, Ziyi, Lu, Weicheng, Lin, Xudong, Xu, Bingzhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418641/
https://www.ncbi.nlm.nih.gov/pubmed/37569705
http://dx.doi.org/10.3390/ijms241512329
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author Hu, Xiaoping
Xie, Jingdun
Yang, Yilin
Qiu, Ziyi
Lu, Weicheng
Lin, Xudong
Xu, Bingzhe
author_facet Hu, Xiaoping
Xie, Jingdun
Yang, Yilin
Qiu, Ziyi
Lu, Weicheng
Lin, Xudong
Xu, Bingzhe
author_sort Hu, Xiaoping
collection PubMed
description Brain tumors have been proved challenging to treat. Here we established a Multi-Target Neural Differentiation (MTND) therapeutic cocktail to achieve effective and safe treatment of brain malignancies by targeting the important hallmarks in brain cancers: poor cell differentiation and compromised cell cycle. In-vitro and in-vivo experiments confirmed the significant therapeutic effect of our MTND therapy. Significantly improved therapeutic effects over current first-line chemo-drugs have been identified in clinical cells, with great inhibition of the growth and migration of tumor cells. Further in-vivo experiments confirmed that sustained MTND treatment showed a 73% reduction of the tumor area. MTND also induced strong expression of phenotypes associated with cell cycle exit/arrest and rapid neural reprograming from clinical glioma cells to glutamatergic and GABAergic expressing cells, which are two key neuronal types involved in many human brain functions, including learning and memory. Collectively, MTND induced multi-targeted genotypic expression changes to achieve direct neural conversion of glioma cells and controlled the cell cycle/tumorigenesis development, helping control tumor cells’ malignant proliferation and making it possible to treat brain malignant tumors effectively and safely. These encouraging results open avenues to developing new therapies for brain malignancies beyond cytotoxic agents, providing more effective medication recommendations with reduced toxicity.
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spelling pubmed-104186412023-08-12 Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor Hu, Xiaoping Xie, Jingdun Yang, Yilin Qiu, Ziyi Lu, Weicheng Lin, Xudong Xu, Bingzhe Int J Mol Sci Article Brain tumors have been proved challenging to treat. Here we established a Multi-Target Neural Differentiation (MTND) therapeutic cocktail to achieve effective and safe treatment of brain malignancies by targeting the important hallmarks in brain cancers: poor cell differentiation and compromised cell cycle. In-vitro and in-vivo experiments confirmed the significant therapeutic effect of our MTND therapy. Significantly improved therapeutic effects over current first-line chemo-drugs have been identified in clinical cells, with great inhibition of the growth and migration of tumor cells. Further in-vivo experiments confirmed that sustained MTND treatment showed a 73% reduction of the tumor area. MTND also induced strong expression of phenotypes associated with cell cycle exit/arrest and rapid neural reprograming from clinical glioma cells to glutamatergic and GABAergic expressing cells, which are two key neuronal types involved in many human brain functions, including learning and memory. Collectively, MTND induced multi-targeted genotypic expression changes to achieve direct neural conversion of glioma cells and controlled the cell cycle/tumorigenesis development, helping control tumor cells’ malignant proliferation and making it possible to treat brain malignant tumors effectively and safely. These encouraging results open avenues to developing new therapies for brain malignancies beyond cytotoxic agents, providing more effective medication recommendations with reduced toxicity. MDPI 2023-08-02 /pmc/articles/PMC10418641/ /pubmed/37569705 http://dx.doi.org/10.3390/ijms241512329 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Xiaoping
Xie, Jingdun
Yang, Yilin
Qiu, Ziyi
Lu, Weicheng
Lin, Xudong
Xu, Bingzhe
Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title_full Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title_fullStr Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title_full_unstemmed Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title_short Multi-Target Neural Differentiation (MTND) Therapeutic Cocktail to Suppress Brain Tumor
title_sort multi-target neural differentiation (mtnd) therapeutic cocktail to suppress brain tumor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418641/
https://www.ncbi.nlm.nih.gov/pubmed/37569705
http://dx.doi.org/10.3390/ijms241512329
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