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Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines

BACKGROUND: This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). METHODS AND MATERIALS: T...

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Autores principales: Dehne, Sarah, Fritz, Clarissa, Rieken, Stefan, Baris, Daniela, Brons, Stephan, Haberer, Thomas, Debus, Jürgen, Weber, Klaus-Josef, Schmid, Thomas E., Combs, Stephanie E., Habermehl, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346564/
https://www.ncbi.nlm.nih.gov/pubmed/28348976
http://dx.doi.org/10.3389/fonc.2017.00035
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author Dehne, Sarah
Fritz, Clarissa
Rieken, Stefan
Baris, Daniela
Brons, Stephan
Haberer, Thomas
Debus, Jürgen
Weber, Klaus-Josef
Schmid, Thomas E.
Combs, Stephanie E.
Habermehl, Daniel
author_facet Dehne, Sarah
Fritz, Clarissa
Rieken, Stefan
Baris, Daniela
Brons, Stephan
Haberer, Thomas
Debus, Jürgen
Weber, Klaus-Josef
Schmid, Thomas E.
Combs, Stephanie E.
Habermehl, Daniel
author_sort Dehne, Sarah
collection PubMed
description BACKGROUND: This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). METHODS AND MATERIALS: The HCC cell lines HepG2, Hep3B, HuH7, and PLC were cultured and irradiated with photons or carbon ions at the Heidelberg Ion Beam Therapy Center using the raster-scanning method. For combination experiments, cell lines were first treated with Temsirolimus or GEM before irradiation. Cytotoxicity was measured by a clonogenic survival assay. The evaluation of the experiments and the obtained survival curves were based on the concept of additivity defined by Steel and Peckham. RESULTS: The results for the combination of carbon ions and both tested systemic substances TEM and GEM showed independent toxicities in all four cell lines. Supra-additive effects were observed in PLC cells for photon irradiation combined either with TEM or GEM and in HuH7 cells for the combination of photons with TEM. CONCLUSION: Addition of targeted therapy substances Temsirolimus and GEM to photon irradiation showed additive cytotoxicity in HCC cell lines, whereas independent toxicities where reached by the combination of carbon ions to these substances. It can be assumed that combining 12C with systemic substances only has independent effects because heavy ions cause direct damage because of their high-LET character resulting in complex and clustered double-strand breaks. Nonetheless, further investigations are warranted in order to determine whether addition of systemic therapy allows a reduction of radiation doses in combination therapy. This could possibly lead to better responses and tolerances in patients with HCC.
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spelling pubmed-53465642017-03-27 Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines Dehne, Sarah Fritz, Clarissa Rieken, Stefan Baris, Daniela Brons, Stephan Haberer, Thomas Debus, Jürgen Weber, Klaus-Josef Schmid, Thomas E. Combs, Stephanie E. Habermehl, Daniel Front Oncol Oncology BACKGROUND: This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). METHODS AND MATERIALS: The HCC cell lines HepG2, Hep3B, HuH7, and PLC were cultured and irradiated with photons or carbon ions at the Heidelberg Ion Beam Therapy Center using the raster-scanning method. For combination experiments, cell lines were first treated with Temsirolimus or GEM before irradiation. Cytotoxicity was measured by a clonogenic survival assay. The evaluation of the experiments and the obtained survival curves were based on the concept of additivity defined by Steel and Peckham. RESULTS: The results for the combination of carbon ions and both tested systemic substances TEM and GEM showed independent toxicities in all four cell lines. Supra-additive effects were observed in PLC cells for photon irradiation combined either with TEM or GEM and in HuH7 cells for the combination of photons with TEM. CONCLUSION: Addition of targeted therapy substances Temsirolimus and GEM to photon irradiation showed additive cytotoxicity in HCC cell lines, whereas independent toxicities where reached by the combination of carbon ions to these substances. It can be assumed that combining 12C with systemic substances only has independent effects because heavy ions cause direct damage because of their high-LET character resulting in complex and clustered double-strand breaks. Nonetheless, further investigations are warranted in order to determine whether addition of systemic therapy allows a reduction of radiation doses in combination therapy. This could possibly lead to better responses and tolerances in patients with HCC. Frontiers Media S.A. 2017-03-13 /pmc/articles/PMC5346564/ /pubmed/28348976 http://dx.doi.org/10.3389/fonc.2017.00035 Text en Copyright © 2017 Dehne, Fritz, Rieken, Baris, Brons, Haberer, Debus, Weber, Schmid, Combs and Habermehl. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Dehne, Sarah
Fritz, Clarissa
Rieken, Stefan
Baris, Daniela
Brons, Stephan
Haberer, Thomas
Debus, Jürgen
Weber, Klaus-Josef
Schmid, Thomas E.
Combs, Stephanie E.
Habermehl, Daniel
Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title_full Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title_fullStr Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title_full_unstemmed Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title_short Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines
title_sort combination of photon and carbon ion irradiation with targeted therapy substances temsirolimus and gemcitabine in hepatocellular carcinoma cell lines
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346564/
https://www.ncbi.nlm.nih.gov/pubmed/28348976
http://dx.doi.org/10.3389/fonc.2017.00035
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