Analysis and variability of TGFbeta measurements in cancer patients with skeletal metastases.
Transforming growth factor beta (TGFbeta) plays an important role in cancer, but accurate measurement of circulating TGFbeta is complicated by the high TGFbeta content of platelets which can release TGFbeta ex vivo. We evaluated the use of citrate-theophylline-adenosine-dipyridamole (CTAD) tubes to reduce preanalytical variation in TGFbeta measurements caused by ex vivo platelet activation. CTAD substantially reduced ex vivo platelet activation relative to traditional plasma collections in normal donors, which correlated with a decrease in measured TGFbeta levels. We show that TGFbeta levels are elevated in the majority of cancer patients with skeletal metastases, and that within-patient variability of these levels is relatively low over several weeks. Patients with elevated TGFbeta could be subdivided into groups with or without evidence of platelet contribution to measured TGFbeta levels. The use of CTAD tubes allows a better determination of a patient's TGFbeta status, and may improve classification of patients with oncologic disease.
O'Brien
Peter J
PJ
Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA;
Ramanathan
Rajeev
R
Yingling
Jonathan M
JM
Baselga
Jose
J
Rothenberg
Mace L
ML
Carducci
Michael
M
Daly
Thomas
T
Adcock
Dorothy
D
Lahn
Michael
M
Clin Chem. 2002 Jun;48(6 Pt 1):891-9
12029005
Clin Cancer Res. 1999 Sep;5(9):2498-505
10499625
Proc Natl Acad Sci U S A. 1985 Apr;82(8):2267-71
3857579
J Cell Biol. 1986 Apr;102(4):1217-23
3457014
BMC Cancer. 2005 Aug 08;5:98
16086840
Nat Rev Cancer. 2003 Nov;3(11):807-21
14557817
Clin Chem. 1997 Oct;43(10):1965-74
9342020
Neoplasia. 2002 Nov-Dec;4(6):465-73
12407439
J Immunol Methods. 1997 Dec 1;209(2):203-6
9461336
Clin Cancer Res. 1995 Jan;1(1):129-36
9815895
Clin Chem. 2004 Mar;50(3):656-8
14981037
Int J Cancer. 2004 Dec 20;112(6):1020-8
15386352
Clin Chem. 2005 Dec;51(12):2365-8
16306098
Clin Chem. 1999 Nov;45(11):2030-3
10545083
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8621-3
12861075
Biomarkers. 2008 Mar;13(2):217-36
18270872
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13909-14
16172383
Clin Cancer Res. 2004 Sep 1;10(17):5804-7
15355909
Blood. 1981 Feb;57(2):199-202
6160890
Anticancer Res. 2005 Sep-Oct;25(5):3523-9
16101174
N Engl J Med. 2000 May 4;342(18):1350-8
10793168
Thromb Res. 1983 Jul 15;31(2):365-74
6636048
Thromb Res. 1996 Aug 1;83(3):199-216
8840462
J Clin Oncol. 2001 Jun 1;19(11):2856-64
11387358