TGF-beta signalling-related markers in cancer patients with bone metastasis.

Abstract

We measured transforming growth factor (TGF)-beta-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-beta 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-beta1 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-beta inhibitor.

• Authors: Jose Baselga, Mace L Rothenberg, Josep Tabernero, Joan Seoane, Thomas Daly, Ann Cleverly, Brandi Berry, Susanne K Rhoades, Chad A Ray, Jeffrey Fill, Daphne L Farrington, Lisa Anne Wallace, Jonathan M Yingling, Michael Lahn, Carlos Arteaga, Michael Carducci
• Journal: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals (Biomarkers) Vol. 13 Issue 2 Pg. 217-36 (Mar 2008) ISSN: 1354-750X [Print] England
• PMID: 18270872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Interleukin-11
• Parathyroid Hormone-Related Protein
• Smad Proteins
• Transforming Growth Factor beta
• Platelet Factor 4

Topics

• Aged
• Biomarkers
• Bone Neoplasms (blood, drug therapy, secondary)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Interleukin-11 (blood)
• Male
• Middle Aged
• Parathyroid Hormone-Related Protein (blood)
• Platelet Factor 4 (blood)
• Signal Transduction
• Smad Proteins (blood)
• Transforming Growth Factor beta (antagonists & inhibitors, blood)