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Intraperitoneal treatment with dimethylthioampal (DIMATE) combined with surgical debulking is effective for experimental peritoneal carcinomatosis in a rat model

  • Published:
Journal of Gastrointestinal Surgery

Abstract

The goal was to evaluate the efficiency of intraperitoneal administration of dimethylthioampal (DIMATE), a cellular apoptosis inducer, combined, or not, with cytoreductive surgery on rats with peritoneal adenocarcinomatosis. Peritoneal carcinomatosis was induced in rats by intraperitoneal injection of adenocarcinoma cell line DHD/K12/pro B. Intraperitoneal DIMATE was given at 17.3 mg/kg. Rats were randomized into five groups of eight animals, regarding the day of treatment (2 days or 20 days after peritoneal carcinomatosis induction) and the combination with cytoreductive surgery. All rats were killed at 30 days to evaluate carcinomatosis extent (quantitative score) and ascites volume. The quantitative score of carcinomatosis and the ascites volume were significantly reduced in the groups treated with DIMATE at day 2 (P = 0.005 and P < 0.001, respectively) and when DIMATE was used with cytoreductive surgery at day 20 (P = 0.009 and P <0.001, respectively). Cytoreductive surgery or DIMATE used alone at day 20 had no significant infiuence. The intraperitoneal DIMATE administration at day 20, when not combined with surgery, had no significant infiuence on carcinomatosis extent or on ascites volume. Intraperitoneal DIMATE appeared to be an efficient drug in the prevention or treatment of peritoneal carcinomatosis when combined with cytoreductive surgery or when it was given by intraperitoneal route, before the development of macroscopic peritoneal carcinomatosis. It appears to be a promising therapeutic agent to be investigated in a human phase I trial in peritoneal carcinomatosis.

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Authors and Affiliations

  1. Service de Chirurgie Digestive d’Urgence, Hô pital Edouard Herriot, Lyon, France

    Olivier Monneuse M.D.

  2. Faculté de Médecine Lyon Sud, EA 3738, Oullins, France

    Olivier Monneuse M.D., Francois Noel Gilly M.D., Ph.D. &  Olivier Glehen M.D., Ph.D.

  3. Service de Chirurgie Générale, CHU de Grenoble, France

    Jean-Philippe Mestrallet M.D.

  4. Faculté de Médecine Lyon Sud, Laboratoire d’Immunochimie, Oullins, France

    Gerry Quash Ph.D.

  5. Service de Chirurgie Générale, Thoracique et Endocrinienne, CHU Lyon Sud, Pierre Bénite, France

    Francois Noel Gilly M.D., Ph.D. &  Olivier Glehen M.D., Ph.D.

Authors
  1. Olivier Monneuse M.D.
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  2. Jean-Philippe Mestrallet M.D.
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  3. Gerry Quash Ph.D.
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  4. Francois Noel Gilly M.D., Ph.D.
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  5. Olivier Glehen M.D., Ph.D.
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Correspondence to Olivier Glehen M.D., Ph.D..

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Monneuse, O., Mestrallet, JP., Quash, G. et al. Intraperitoneal treatment with dimethylthioampal (DIMATE) combined with surgical debulking is effective for experimental peritoneal carcinomatosis in a rat model. J Gastrointest Surg 9, 769–774 (2005). https://doi.org/10.1016/j.gassur.2005.02.006

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  • DOI: https://doi.org/10.1016/j.gassur.2005.02.006

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