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A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas

Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resis...

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Autores principales: Adams, Olivia, Janser, Félice A., Dislich, Bastian, Berezowska, Sabina, Humbert, Magali, Seiler, Christian A., Kroell, Dino, Slotta-Huspenina, Julia, Feith, Marcus, Ott, Katja, Tschan, Mario P., Langer, Rupert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999293/
https://www.ncbi.nlm.nih.gov/pubmed/29897944
http://dx.doi.org/10.1371/journal.pone.0197610
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author Adams, Olivia
Janser, Félice A.
Dislich, Bastian
Berezowska, Sabina
Humbert, Magali
Seiler, Christian A.
Kroell, Dino
Slotta-Huspenina, Julia
Feith, Marcus
Ott, Katja
Tschan, Mario P.
Langer, Rupert
author_facet Adams, Olivia
Janser, Félice A.
Dislich, Bastian
Berezowska, Sabina
Humbert, Magali
Seiler, Christian A.
Kroell, Dino
Slotta-Huspenina, Julia
Feith, Marcus
Ott, Katja
Tschan, Mario P.
Langer, Rupert
author_sort Adams, Olivia
collection PubMed
description Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC.
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spelling pubmed-59992932018-06-21 A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas Adams, Olivia Janser, Félice A. Dislich, Bastian Berezowska, Sabina Humbert, Magali Seiler, Christian A. Kroell, Dino Slotta-Huspenina, Julia Feith, Marcus Ott, Katja Tschan, Mario P. Langer, Rupert PLoS One Research Article Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC. Public Library of Science 2018-06-13 /pmc/articles/PMC5999293/ /pubmed/29897944 http://dx.doi.org/10.1371/journal.pone.0197610 Text en © 2018 Adams et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Adams, Olivia
Janser, Félice A.
Dislich, Bastian
Berezowska, Sabina
Humbert, Magali
Seiler, Christian A.
Kroell, Dino
Slotta-Huspenina, Julia
Feith, Marcus
Ott, Katja
Tschan, Mario P.
Langer, Rupert
A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title_full A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title_fullStr A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title_full_unstemmed A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title_short A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
title_sort specific expression profile of lc3b and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999293/
https://www.ncbi.nlm.nih.gov/pubmed/29897944
http://dx.doi.org/10.1371/journal.pone.0197610
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