Wagner, Markus; Roh, Vincent; Strehlen, Michael; Laemmle, Alexander; Stroka, Deborah; Egger, Bernhard; Trochsler, Markus; Hunt, Kelly K; Candinas, Daniel; Vorburger, Stephan A (2009). Effective treatment of advanced colorectal cancer by rapamycin and 5-FU/oxaliplatin monitored by TIMP-1. Journal of gastrointestinal surgery, 13(10), pp. 1781-90. New York, N.Y.: Springer-Verlag 10.1007/s11605-009-0948-x
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery |
UniBE Contributor: |
Lämmle, Alexander, Stroka, Deborah, Candinas, Daniel, Vorburger, Stephan |
ISSN: |
1091-255X |
Publisher: |
Springer-Verlag |
Language: |
English |
Submitter: |
Anette van Dorland |
Date Deposited: |
04 Oct 2013 15:12 |
Last Modified: |
05 Dec 2022 14:22 |
Publisher DOI: |
10.1007/s11605-009-0948-x |
PubMed ID: |
19565301 |
Web of Science ID: |
000270363400005 |
BORIS DOI: |
10.7892/boris.31848 |
URI: |
https://boris.unibe.ch/id/eprint/31848 (FactScience: 196611) |
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