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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 Tang, Daolin

PloS one, 2018-06, Vol.13 (6), p.e0197610-e0197610 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
Autor: 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
Tang, Daolin
Assuntos: Adenocarcinoma ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Adult ; Aged ; Apoptosis ; Autophagy ; Autophagy (Cytology) ; Autophagy - genetics ; Biology and Life Sciences ; Biopsy ; Biotechnology ; Cancer ; Cancer therapies ; Care and treatment ; Cell death ; Cell division ; Chemoresistance ; Chemotherapy ; Development and progression ; Disease-Free Survival ; Esophageal cancer ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - pathology ; Esophagus ; Experiments ; Female ; Gastric cancer ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Histology ; Homeostasis ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; Kinases ; Male ; Medical prognosis ; Medicine and Health Sciences ; Microtubule-Associated Proteins - genetics ; Middle Aged ; mRNA ; Neoadjuvant Therapy - adverse effects ; Ovarian cancer ; Paclitaxel ; Paclitaxel - administration & dosage ; Paclitaxel - adverse effects ; Pathology ; Penicillin ; Phagocytosis ; Proteins ; Research and Analysis Methods ; RNA-Binding Proteins - genetics ; Stomach cancer ; Surgery ; Therapeutic applications ; Transcription Factors ; Tumor proteins ; Tumors
É parte de: PloS one, 2018-06, Vol.13 (6), p.e0197610-e0197610
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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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 Tang, Daolin

United States: Public Library of Science

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