Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression

Abstract

BackgroundHyaluronic 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.MethodsWe 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.ResultsWe 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.ConclusionsFor 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.

Mesenchymal stromal cells release CXCL1/2/8 and induce chemoresistance and macrophage polarization

“…We waited 10 days before beginning the treatment, in order to allow the OTCs to interact with and potentially activate the BM-MSCs so to be as close as possible to the ex vivo experiment previously shown. We evaluated tumor progression seven days after the last injection of carboplatin by measuring the peritoneal cancer index (Table 1) as previously described [30]. Briefly, we analyzed the number of nodules and the size of the biggest nodule (as depicted in Table 1) and calculated the peritoneal cancer index.…”

Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane

“…For example, an antiadhesion barrier membrane is essential after intra-abdominal surgery to prevent normally free-moving tissues from sticking together [1]. For successful dental implant surgery, it is important to maintain adequate alveolar ridge dimensions and it often requires guided bone regeneration (GBR).…”

“…However, the lubricating effect of HA is generally short-lived and the duration of its bioeffects is not predictable. To address these issues, a semisynthetic natural polymer obtained from the CMC combined with HA has been developed that can generate a new hybrid membrane for use as a tissue barrier [1, 14, 21]. The CMC can cross-link with HA by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) with a various cross-linking degree [22].…”

Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer

“…The competitive inhibition of PtNP* uptake by HA, consistent with other studies of HA-based NPs [35, 36], suggests that the NPs entered cells via receptors for HA. CD44 is one of the best known receptors for HA [37], expressed on the surface of various cancer cells [38–42] including SKOV3 cells [43, 44]. This result indicates that PtNPs released during the HA gel degradation may provide a selective effect on cancer cells overexpressing HA receptors such as CD44.…”