Adolfo López-Ornelas1, Paula Vergara2, José Segovia3. 1. Departamento de Farmacología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F. 2. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F. 3. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F.. Electronic address: jsegovia@fisio.cinvestav.mx.
Abstract
BACKGROUND AIMS: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor and current treatments have not improved its prognosis. Therefore, new strategies and therapeutic agents should be investigated. Growth arrest specific-1 (Gas1) is a protein that induces cell arrest and apoptosis of gliomas and a soluble form, tGas1, increases these effects acting in both autocrine and paracrine manners. Moreover, neural stem cells (NSCs) can be used as a vehicle to transport therapeutic molecules because they have innate tropism towards tumors. METHODS: Lentiviral vectors were used to obtain NSCs capable of expressing tGas1 in a regulated manner. The ability of engineered NSCs to track and reach GBM in vivo, produce tGas1, and their efficacy decreasing tumor growth and increasing the overall health and survival time of nude mice implanted with GBM were assessed. RESULTS: The overexpression of tGas1 from NSCs decreased viability and induced cell arrest and apoptosis of GBM cells and also, albeit in a reduced manner, of NSCs themselves. NSCs migrate from one cerebral hemisphere to the contralateral, reach GBM, express the tGas1 transgene when induced by tetracycline and produce the protein. Tumor volume decreased by 77% compared with controls, and tGas1 improved the overall health and increased the survival time of mice implanted with GBM by 75%. CONCLUSIONS: We demonstrated that tGas1 has an antineoplastic effect, and the results support the potential of tGas1 as an adjuvant for the treatment of gliomas.
BACKGROUND AIMS: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor and current treatments have not improved its prognosis. Therefore, new strategies and therapeutic agents should be investigated. Growth arrest specific-1 (Gas1) is a protein that induces cell arrest and apoptosis of gliomas and a soluble form, tGas1, increases these effects acting in both autocrine and paracrine manners. Moreover, neural stem cells (NSCs) can be used as a vehicle to transport therapeutic molecules because they have innate tropism towards tumors. METHODS: Lentiviral vectors were used to obtain NSCs capable of expressing tGas1 in a regulated manner. The ability of engineered NSCs to track and reach GBM in vivo, produce tGas1, and their efficacy decreasing tumor growth and increasing the overall health and survival time of nude mice implanted with GBM were assessed. RESULTS: The overexpression of tGas1 from NSCs decreased viability and induced cell arrest and apoptosis of GBM cells and also, albeit in a reduced manner, of NSCs themselves. NSCs migrate from one cerebral hemisphere to the contralateral, reach GBM, express the tGas1 transgene when induced by tetracycline and produce the protein. Tumor volume decreased by 77% compared with controls, and tGas1 improved the overall health and increased the survival time of mice implanted with GBM by 75%. CONCLUSIONS: We demonstrated that tGas1 has an antineoplastic effect, and the results support the potential of tGas1 as an adjuvant for the treatment of gliomas.
Authors: Brenda I Luna-Antonio; Rafael Rodriguez-Muñoz; Carmen Namorado-Tonix; Paula Vergara; Jose Segovia; Jose L Reyes Journal: Histochem Cell Biol Date: 2017-03-18 Impact factor: 4.304
Authors: Brenda I Luna-Antonio; Rafael Rodríguez-Muñoz; Carmen Namorado-Tonix; Alejandro Pérez-López; Elsa I Sanchez; Paula Vergara; José L Reyes; José Segovia Journal: J Mol Histol Date: 2022-10-22 Impact factor: 3.156
Authors: Elizabeth Bautista; Natanael Zarco; Nicolás Aguirre-Pineda; Manuel Lara-Lozano; Paula Vergara; Juan Antonio González-Barrios; Raúl Aguilar-Roblero; José Segovia Journal: Cell Mol Neurobiol Date: 2017-11-06 Impact factor: 5.046
Authors: Gina Li; Nicolas Bonamici; Mahua Dey; Maciej S Lesniak; Irina V Balyasnikova Journal: Expert Opin Drug Deliv Date: 2017-09-18 Impact factor: 6.648