Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.

<h4>Background</h4>The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung per...

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Autores principales:	Pierre-Benoit Pagès, Olivier Facy, Pierre Mordant, Sylvain Ladoire, Guy Magnin, Francois Lokiec, Francois Ghiringhelli, Alain Bernard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/578522b4bac34285bbab7d56024f5fb8
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spelling	oai:doaj.org-article:578522b4bac34285bbab7d56024f5fb82021-11-18T07:53:05ZIsolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.1932-620310.1371/journal.pone.0059485https://doaj.org/article/578522b4bac34285bbab7d56024f5fb82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527205/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP.<h4>Methods</h4>First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria.<h4>Results</h4>In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent.<h4>Conclusions</h4>GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique.Pierre-Benoit PagèsOlivier FacyPierre MordantSylvain LadoireGuy MagninFrancois LokiecFrancois GhiringhelliAlain BernardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59485 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre-Benoit Pagès Olivier Facy Pierre Mordant Sylvain Ladoire Guy Magnin Francois Lokiec Francois Ghiringhelli Alain Bernard Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
description	<h4>Background</h4>The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP.<h4>Methods</h4>First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria.<h4>Results</h4>In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent.<h4>Conclusions</h4>GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique.
format	article
author	Pierre-Benoit Pagès Olivier Facy Pierre Mordant Sylvain Ladoire Guy Magnin Francois Lokiec Francois Ghiringhelli Alain Bernard
author_facet	Pierre-Benoit Pagès Olivier Facy Pierre Mordant Sylvain Ladoire Guy Magnin Francois Lokiec Francois Ghiringhelli Alain Bernard
author_sort	Pierre-Benoit Pagès
title	Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
title_short	Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
title_full	Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
title_fullStr	Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
title_full_unstemmed	Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
title_sort	isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/578522b4bac34285bbab7d56024f5fb8
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Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.

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