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Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth

Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing fact...

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Autores principales: Ranjan, Alok, Wright, Stephen, Srivastava, Sanjay K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564593/
https://www.ncbi.nlm.nih.gov/pubmed/28512255
http://dx.doi.org/10.18632/oncotarget.17425
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author Ranjan, Alok
Wright, Stephen
Srivastava, Sanjay K
author_facet Ranjan, Alok
Wright, Stephen
Srivastava, Sanjay K
author_sort Ranjan, Alok
collection PubMed
description Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics. Penfluridol, an antipsychotic drug has been shown to have anti-cancer properties in our recently published studies. The present study evaluates the immune response of penfluridol in glioblastoma tumors. Our results demonstrated that penfluridol treatment significantly suppressed glioblastoma tumor growth. Our current results demonstrated about 72% suppression of myeloid derived suppressor cells (MDSCs) with penfluridol treatment in mouse bearing U87MG glioblastoma tumors. MDSCs are known to increase regulatory T cells (Treg), which are immunosuppressive in nature and suppresses M1 macrophages that are tumor suppressive in nature. Our results also showed suppression of regulatory T cells as well as elevation of M1 macrophages with penfluridol treatment by 58% and 57% respectively. Decrease in CCL4 as well as IFNγ with penfluridol treatment was also observed indicating decrease in overall tumor inflammation. This is the first report demonstrating immune modulations by penfluridol treatment associated with glioblastoma tumor growth suppression prompting further investigation to establish penfluridol as a treatment option for glioblastoma patients.
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spelling pubmed-55645932017-08-23 Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth Ranjan, Alok Wright, Stephen Srivastava, Sanjay K Oncotarget Research Paper Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics. Penfluridol, an antipsychotic drug has been shown to have anti-cancer properties in our recently published studies. The present study evaluates the immune response of penfluridol in glioblastoma tumors. Our results demonstrated that penfluridol treatment significantly suppressed glioblastoma tumor growth. Our current results demonstrated about 72% suppression of myeloid derived suppressor cells (MDSCs) with penfluridol treatment in mouse bearing U87MG glioblastoma tumors. MDSCs are known to increase regulatory T cells (Treg), which are immunosuppressive in nature and suppresses M1 macrophages that are tumor suppressive in nature. Our results also showed suppression of regulatory T cells as well as elevation of M1 macrophages with penfluridol treatment by 58% and 57% respectively. Decrease in CCL4 as well as IFNγ with penfluridol treatment was also observed indicating decrease in overall tumor inflammation. This is the first report demonstrating immune modulations by penfluridol treatment associated with glioblastoma tumor growth suppression prompting further investigation to establish penfluridol as a treatment option for glioblastoma patients. Impact Journals LLC 2017-04-26 /pmc/articles/PMC5564593/ /pubmed/28512255 http://dx.doi.org/10.18632/oncotarget.17425 Text en Copyright: © 2017 Ranjan et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ranjan, Alok
Wright, Stephen
Srivastava, Sanjay K
Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title_full Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title_fullStr Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title_full_unstemmed Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title_short Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
title_sort immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564593/
https://www.ncbi.nlm.nih.gov/pubmed/28512255
http://dx.doi.org/10.18632/oncotarget.17425
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