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Biomarkers Volume 13, 2008 - Issue 2
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Research Article

TGF-β signalling-related markers in cancer patients with bone metastasis

Jose Baselga Vall d′Hebron University Hospital, 08035, Barcelona, Spain
,
Mace L. Rothenberg Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232, USA
,
Josep Tabernero Vall d′Hebron University Hospital, 08035, Barcelona, Spain
,
Joan Seoane Vall d′Hebron University Hospital, 08035, Barcelona, Spain
,
Thomas Daly Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Ann Cleverly Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Brandi Berry Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Susanne K. Rhoades Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Chad A. Ray Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Jeffrey Fill Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Daphne L. Farrington Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Lisa Anne Wallace The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, 21205, USA
,
Jonathan M. Yingling Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Michael Lahn Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA
,
Carlos Arteaga Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232, USA
&
Michael Carducci The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, 21205, USA
 show all
Pages 217-236 | Received 14 May 2007, Published online: 08 Oct 2008
 
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Abstract

We measured transforming growth factor (TGF)-β-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-β inhibitors. Forty-nine patients with bone metastasis were enrolled in the study, including patients with breast (n=23) and prostate cancer (n=15). Plasma TGF-β1 levels were elevated in more than half of the cancer patients (geometric mean 2.63 ng ml−1) and positively correlated with increased platelet factor 4 (PF4) levels, parathyroid-related protein (PTHrP), von Willebrand Factor (vWF) and interleukin (IL)-10. PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-β inhibitor.

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