La thérapie photodynamique pour le traitement des maladies inflammatoires chroniques de l'intestin et la prévention des cancers colorectaux associés : évaluation sur modèles murins

Abstract : Inflammatory bowel diseases (IBD) are chronic, incurable diseases associated with a high risk of colorectal cancer. Currently available therapies for the treatment of IBD and CRC prevention are far from optimal. Recently, photodynamic therapy (PDT) using low doses of photosensitizer and/or light, called LDPDT (Low-dose PDT) has emerged as a new treatment modality for inflammatory diseases such as psoriasis or rheumatoid arthritis. In this study, we assessed the therapeutic effect of LDPDT using a liposomal formulation of mTHPC (meta-tetra-hydroxyphenylchlorin, called Foslip®) in the mouse model for the treatment of IBD and prevention of CRC. Endoscopic, macroscopic and histological analyzes were performed and the rate of myeloperoxidase (MPO) in the colonic mucosa was quantified by ELISA. Cytokine expressions were quantified by RT-PCR, the permeability of the intestinal barrier was evaluated by immunolabeling and intestinal microbiota analysis was done by pyrosequencing. LDPDT-Foslip® significantly reduced colitis severity by suppressing intestinal inflammation including reduction of proinflammatory cytokines and suppression of neutrophil influx. Moreover, LDPDT restores the integrity of the intestinal barrier. In addition, LDPDT-Foslip® has clearly demonstrated a preventive effect on colorectal cancer development by suppressing chronic inflammation and changing the composition of intestinal microbiota. Accordingly, LDPDT-Foslip® could be considered as a new treatment modality to abrogate intestinal inflammation and prevent the development of colorectal cancer in patients with IBD
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Theses
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http://docnum.univ-lorraine.fr/prive/DDOC_T_2014_0177_REINHARD.pdf
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https://hal.univ-lorraine.fr/tel-01751070
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Submitted on : Thursday, March 29, 2018 - 1:04:34 PM
Last modification on : Friday, March 30, 2018 - 1:30:37 AM

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  • HAL Id : tel-01751070, version 1

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Aurélie Reinhard. La thérapie photodynamique pour le traitement des maladies inflammatoires chroniques de l'intestin et la prévention des cancers colorectaux associés : évaluation sur modèles murins. Médecine humaine et pathologie. Université de Lorraine, 2014. Français. ⟨NNT : 2014LORR0177⟩. ⟨tel-01751070⟩

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