D García-Olmo1,2,3, P Villarejo Campos4, J Barambio2, S Garcia Gomez-Heras5, L Vega-Clemente1, S Olmedillas-Lopez1, H Guadalajara2,3, M Garcia-Arranz1,3. 1. New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain. 2. Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040, Madrid, Spain. 3. Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034, Madrid, Spain. 4. Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040, Madrid, Spain. villarejocampos@yahoo.es. 5. Department of Human Histology, Universidad Rey Juan Carlos, Avda de Atenas s/n, 28922, Alcorcón, Spain.
Abstract
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to pan class="Chemical">mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.
Authors: Jaehwa Choi; Kimberly Credit; Karla Henderson; Ravi Deverkadra; Zhi He; Helge Wiig; Heather Vanpelt; Michael F Flessner Journal: Clin Cancer Res Date: 2006-03-15 Impact factor: 12.531
Authors: M Garcia-Arranz; P Villarejo-Campos; J Barambio; S Garcia Gomez-Heras; L Vega-Clemente; H Guadalajara; D García-Olmo Journal: World J Surg Oncol Date: 2022-02-25 Impact factor: 2.754