TY - JOUR
T1 - Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice
AU - Jansen, Burkhard
AU - Heere-Ress, Elisabeth
AU - Schlagbauer-Wadl, Hermine
AU - Halaschek-Wiener, Julius
AU - Waltering, Stephan
AU - Moll, Ingrid
AU - Pehamberger, Hubert
AU - Marciano, Daniele
AU - Kloog, Yoel
AU - Wolff, Klaus
N1 - Funding Information:
Acknowledgements We thank the members of the Center for Biomedical Research, University of Vienna, Vienna, Austria, in particular, H. Pischinger, H. Bergmeister and U. Losert, for outstanding animal care and continuing support, and H. Kahr (University of Vienna) for technical assistance. Additionally we are grateful to T. Lucas (University of Vienna) for helpful discussions and critically reviewing the manuscript. Work in the laboratory of B.J. is supported by the Austrian Science Fund, the Austrian National Bank, the “Kommission Onkologie,” the “Kamillo Eisner Stiftung,” the “Anton Dreher Stiftung,” and the Niarchos Foundation. Work in the group of Y.K. was supported by the “Friends of the University of Tel-Aviv in Austria” and by the SAFAHO Foundation.
PY - 1999
Y1 - 1999
N2 - Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32±0.15 g and 1.08±0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.
AB - Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32±0.15 g and 1.08±0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.
KW - Merkel cell carcinoma
KW - S-trans, trans-farnesylthiosalicylic acid
KW - SCID mouse
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=0033400494&partnerID=8YFLogxK
U2 - 10.1007/s001099900052
DO - 10.1007/s001099900052
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AN - SCOPUS:0033400494
SN - 0946-2716
VL - 77
SP - 792
EP - 797
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 11
ER -
