title: 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.affiliation: Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Joan
authors.initials: J
authors.lastname: Seoane
authors.forename: Thomas
authors.initials: T
authors.lastname: Daly
authors.forename: Ann
authors.initials: A
authors.lastname: Cleverly
authors.forename: Brandi
authors.initials: B
authors.lastname: Berry
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Rhoades
authors.forename: Chad A
authors.initials: CA
authors.lastname: Ray
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fill
authors.forename: Daphne L
authors.initials: DL
authors.lastname: Farrington
authors.forename: Lisa Anne
authors.initials: LA
authors.lastname: Wallace
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Yingling
authors.forename: Michael
authors.initials: M
authors.lastname: Lahn
authors.forename: Carlos
authors.initials: C
authors.lastname: Arteaga
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
mesh_terms: D000368:Aged; D015415:Biomarkers; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000097:blood; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood; D010978:Platelet Factor 4 / Q000097:blood; D015398:Signal Transduction; D051785:Smad Proteins / Q000097:blood; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D015415:Biomarkers; D017370:Interleukin-11; D044162:Parathyroid Hormone-Related Protein; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D010978:Platelet Factor 4