title: Epigenetic effects of chromatin remodeling agents on organotypic cultures.
abstract: BACKGROUND
  Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression.
  
  
  CONCLUSIONS
  Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture.
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Sirchia
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Faversani
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rovina
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Russo
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.|Department of Pathophysiology & Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Paganini
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Savi
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.|Department of Pathophysiology & Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.affiliation: Division of Thoracic Surgery & Lung Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rosso
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Del Gobbo
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.|Department of Pathophysiology & Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.|Department of Pathophysiology & Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.|Department of Pathophysiology & Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Miozzo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000556:secondary; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D011401:Promoter Regions, Genetic; D059016:Tumor Microenvironment
chemical_list: D056572:Histone Deacetylase Inhibitors
keywords: DNA hydroxymethylation; DNA methylation; HDAC; chromatin remodeling agents; epigenetics; organotypic culture