Author of

• 20158

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  P1.09 - Mesothelioma (ID 695)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22734

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    P1.09-012 - A Pre-Clinical Investigation of Intrapleural Curcumin Treatments as an Adjunct Therapy for Malignant Pleural Mesothelioma (ID 9312)

    09:30 - 09:30  |  Author(s): S. Marri
    • Abstract

    Background:
    Malignant pleural mesothelioma (MPM) is an aggressive malignancy originating in pleural mesothelial cells with median survivals of approximately 12 months following diagnosis. Recently, anti-angiogenic therapies have been trialled with only a modest effect. This may be, in part, due to alternative mechanisms of tumour vascularisation such as vasculogenic mimicry (VM), the ability of tumour cells to form fluid carrying vascular channels. Curcumin, a polyphenol extracted from the spice turmeric, has numerous anti-cancer and anti-inflammatory properties. Our aims were to investigate the effect of curcumin on vasculogenic mimicry and to determine if curcumin acts by disrupting microRNA profiles of mesothelioma cells. In preparation for future clinical trials, we evaluated the safety of curcumin treatments in vivo, when applied to the pleural cavity.
    
    Method:
    Mesothelioma cell lines NCl-H226 and NCI-H28, as well as patient-derived primary mesothelioma cells isolated from pleural effusions, were used for in vitro experiments. Matrigel tube formation assays were performed to assess if curcumin could inhibit VM in vitro. Small RNAseq was performed to determine if 6 h curcumin (20 mM) treatments had an effect on microRNA expression. Curcumin (80 mg/kg) was injected into the pleural cavity of Fischer 344 rats (n=6) and blood was taken at 1.5 h, 24 h, 48 h, 7 days, 14 days and 21 days. Rats were euthanized at 48 h, 1 week and 3 weeks (n=2). Parietal pleura, lung, kidney, liver brain and heart tissues were obtained and examined for signs of gross tissue damage and histopathological changes such as inflammation, and necrosis. Curcumin plasma and concentrations were measured using UPLC-MS to determine systemic distribution of curcumin following intrapleural treatments.
    
    Result:
    Non-cytotoxic curcumin treatments (20-10 mM) significantly inhibited the ability of mesothelioma cells to perform vasculogenic mimicry in vitro in a dose dependent manner. The microRNA expression profiles differed greatly between each mesothelioma sub-type. Minimal curcumin-induced change was observed, however differential expression analysis revealed some potential microRNA targets. No adverse effects were observed following intrapleural curcumin administration. Encapsulated curcumin deposits were observed in the pleural cavity of rats at 1 and 3 weeks following curcumin administration. Histological analysis revealed focal reactive mesothelial hyperplasia and a histiocytic response towards curcumin. Lung, liver, heart, brain and kidney tissues all display normal histological appearances. Curcumin was detected in the plasma samples of rats receiving intrapleural curcumin with peak concentration observed at 1.5 h post curcumin treatment (387-100 µg/ml).
    
    Conclusion:
    Intrapleural curcumin treatments may be suitable as adjunct treatment for MPM.