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Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR

We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status...

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Autores principales: Caraglia, M, Giuberti, G, Marra, M, Addeo, R, Montella, L, Murolo, M, Sperlongano, P, Vincenzi, B, Naviglio, S, Prete, S Del, Abbruzzese, A, Stiuso, P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122065/
https://www.ncbi.nlm.nih.gov/pubmed/21525937
http://dx.doi.org/10.1038/cddis.2011.34
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author Caraglia, M
Giuberti, G
Marra, M
Addeo, R
Montella, L
Murolo, M
Sperlongano, P
Vincenzi, B
Naviglio, S
Prete, S Del
Abbruzzese, A
Stiuso, P
author_facet Caraglia, M
Giuberti, G
Marra, M
Addeo, R
Montella, L
Murolo, M
Sperlongano, P
Vincenzi, B
Naviglio, S
Prete, S Del
Abbruzzese, A
Stiuso, P
author_sort Caraglia, M
collection PubMed
description We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status in PBMC could be predictive of response. In the 20 responsive patients, the decrease of reactive oxygen species levels was already detectable after 10 days (T10) from the beginning of sorafenib administration, and this effect was enhanced by the combined treatment with sorafenib+octreotide LAR (T21). This effect correlated with the modulation of superoxide dismutase (SOD) activity (physiological scavenger of O(2−)) and of serum nitric oxide (NO) levels. Sorafenib alone induced an increase of about 40% of NO levels and of about two-fold of SOD activity in responsive patients, and both effects were significantly potentiated by the combined treatment. We found a gradual reduction of Erk1/2 activity, as evaluated by cytofluorimetric analysis, in 15 responsive patients reaching about 50% maximal decrease at T21. On the other hand, in 17 resistant patients, Erk1/2 activity was about 80% increased at T21. The determination of both the oxidative stress status and pERK activity in PBMC has high value in the prediction of response to sorafenib+octreotide therapy in HCC patients.
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spelling pubmed-31220652011-07-05 Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR Caraglia, M Giuberti, G Marra, M Addeo, R Montella, L Murolo, M Sperlongano, P Vincenzi, B Naviglio, S Prete, S Del Abbruzzese, A Stiuso, P Cell Death Dis Original Article We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status in PBMC could be predictive of response. In the 20 responsive patients, the decrease of reactive oxygen species levels was already detectable after 10 days (T10) from the beginning of sorafenib administration, and this effect was enhanced by the combined treatment with sorafenib+octreotide LAR (T21). This effect correlated with the modulation of superoxide dismutase (SOD) activity (physiological scavenger of O(2−)) and of serum nitric oxide (NO) levels. Sorafenib alone induced an increase of about 40% of NO levels and of about two-fold of SOD activity in responsive patients, and both effects were significantly potentiated by the combined treatment. We found a gradual reduction of Erk1/2 activity, as evaluated by cytofluorimetric analysis, in 15 responsive patients reaching about 50% maximal decrease at T21. On the other hand, in 17 resistant patients, Erk1/2 activity was about 80% increased at T21. The determination of both the oxidative stress status and pERK activity in PBMC has high value in the prediction of response to sorafenib+octreotide therapy in HCC patients. Nature Publishing Group 2011-04 2011-04-28 /pmc/articles/PMC3122065/ /pubmed/21525937 http://dx.doi.org/10.1038/cddis.2011.34 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Caraglia, M
Giuberti, G
Marra, M
Addeo, R
Montella, L
Murolo, M
Sperlongano, P
Vincenzi, B
Naviglio, S
Prete, S Del
Abbruzzese, A
Stiuso, P
Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title_full Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title_fullStr Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title_full_unstemmed Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title_short Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR
title_sort oxidative stress and erk1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide lar
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122065/
https://www.ncbi.nlm.nih.gov/pubmed/21525937
http://dx.doi.org/10.1038/cddis.2011.34
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