Int J Colorectal Dis (2006) 21: 625–631 DOI 10.1007/s00384-005-0071-8
Janindra Warusavitarne Palaniappan Ramanathan Anthony Kaufman Bruce G. Robinson Margaret Schnitzler
Accepted: 7 December 2005 Published online: 24 March 2006 # Springer-Verlag 2006
J. Warusavitarne (*) . P. Ramanathan . B. G. Robinson . M. Schnitzler Department of Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St. Leonards, NSW 2065, Australia e-mail:
[email protected] Tel.: +61-2-99267176 Fax: +61-2-99268484 A. Kaufman Department of Anatomical Pathology, Palms, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
ORIGINA L ARTI CLE
5-Fluorouracil (5FU) treatment does not influence invasion and metastasis in microsatellite unstable (MSI-H) colorectal cancer
Abstract Microsatellite instability is a recognised pathway of colorectal carcinogenesis responsible for about 15% of all sporadic colorectal cancers. Recent evidence has suggested that these tumours may not have the same response as microsatellite stable colon cancers to 5-fluorouracil (5FU)-based chemotherapy. The response to 5FU in four microsatellite unstable (MSI-H) cell lines was examined by cell viability assays and invasion assays. Flow cytometry was used to assess the effect of 5FU on MSI-H cell lines. In vivo response to 5FU was assessed by intraperitoneal injection of 5FU or control to 80 nude mice that had received intrasplenic injections of an MSI-H cell line KM12C prior to commencing treatment. There was inhibition of cell growth in MSI-H cell lines when treated with 5FU. There was no difference in invasiveness in the MSI-H cell lines when treated with 5FU. Primary tumours formed in 27 of
Introduction There are at least two recognised pathways of colorectal carcinogenesis. About 15% of colorectal cancers demonstrate microsatellite instability, in which point mutations at microsatellite repeat loci result in widespread genomic instability [1, 2]. Tumours with high-frequency microsatellite instability (MSI-H) tend to be locally advanced and are less likely to metastasise than microsatellite stable (MSS) colon cancers.
the untreated and 25 of the 5FU treated mice (p=NS). There was a 36% reduction in splenic weight in those mice treated with 5FU (p
