Fulltext

Effective Treatment of Advanced Colorectal Cancer by Rapamycin and 5-FU/Oxaliplatin Monitored by TIMP-1

Wagner, Markus ; Roh, Vincent ; Strehlen, Michael ; Laemmle, Alexander ; Stroka, Deborah ; Egger, Bernhard ; Trochsler, Markus ; Hunt, Kelly ; Candinas, Daniel ; Vorburger, Stephan

In: Journal of Gastrointestinal Surgery, 2009, vol. 13, no. 10, p. 1781-1790

Aggiungi alla tua lista
    Titre
    • Effective Treatment of Advanced Colorectal Cancer by Rapamycin and 5-FU/Oxaliplatin Monitored by TIMP-1
    Auteur
    • Wagner, Markus. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Roh, Vincent. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Strehlen, Michael. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Laemmle, Alexander. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Stroka, Deborah. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Egger, Bernhard. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Trochsler, Markus. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Hunt, Kelly. Department of Surgical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
    • Candinas, Daniel. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    • Vorburger, Stephan. Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Journal of Gastrointestinal Surgery, 2009, vol. 13, no. 10, p. 1781-1790. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:319098
    Summary
    Aim: The mTOR-inhibitor rapamycin has shown antitumor activity in various tumors. Bedside observations have suggested that rapamycin may be effective as a treatment for colorectal carcinomatosis. Methods: We established an orthotopic syngenic model by transplanting CT26 peritoneal tumors in Balb/C mice and an orthotopic xenograft model by transplanting SW620 peritoneal tumors in nu/nu mice. Expression levels of tissue inhibitor of matrix-metalloproteinases 1 (TIMP-1) in the tumor and serum was determined by enzyme-linked immunosorbent assay. Results: Rapamycin significantly suppressed growth of syngenic and xenografted peritoneal tumors. The effect was similar with intraperitoneal or oral rapamycin administration. Tumor suppression was further enhanced when rapamycin was combined with 5-fluorouracil and/or oxaliplatin. The combination treatment showed no acute toxicity. TIMP-1 serum levels correlated well (CC = 0.75; P < 0.01) with rapamycin treatment. Conclusions: Rapamycin suppressed advanced stage colorectal cancer, even with oral administration. Combining rapamycin with current chemotherapy regimens significantly increased antitumor efficacy without apparent toxicity. The treatment efficacy correlated with serum TIMP-1 levels, suggesting its potential as a surrogate marker in future clinical trials