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 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)

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; Keogh-Stroka, Deborah M.; Candinas, Daniel and Vorburger, Stephan

ISSN:

1091-255X

Publisher:

Springer-Verlag

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:12

Last Modified:

23 Oct 2019 19:25

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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