title: Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression.
abstract: BACKGROUND
  Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study's objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management.
  
  
  METHODS
  We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts.
  
  
  RESULTS
  We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier.
  
  
  CONCLUSIONS
  For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks.
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France ; Surgery Department, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Picaud
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Thibault
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Mery
authors.affiliation: Biostatistic Unit, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Monia
authors.initials: M
authors.lastname: Ouali
authors.affiliation: Surgery Department, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martinez
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France ; Université de Toulouse, Université Paul Sabatier, 118, Route de Narbonne, F-31062 Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Delord
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France ; Université de Toulouse, Université Paul Sabatier, 118, Route de Narbonne, F-31062 Toulouse, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
authors.affiliation: EA4553, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France ; Surgery Department, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052 Toulouse, France.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Ferron
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005069:Evaluation Studies as Topic; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015398:Signal Transduction; D000267:Tissue Adhesions / Q000517:prevention & control
chemical_list: C497483:CD44 protein, human; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid; D002266:Carboxymethylcellulose Sodium
keywords: Anti-adhesion membranes; Hyaluronic acid; Ovarian adenocarcinoma; Surgery
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