title: Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors.
abstract: The chymotrypsin-like (ChT-L) activity is one of the key regulators of intracellular protein degradation. Elevated proteasome ChT-L activity has recently been reported in plasma of patients with leukemia and myelodysplastic syndrome and suggested to have a prognostic significance. The aim of the present study was to evaluate plasma proteasome ChT-L activity in patients with newly diagnosed solid tumors at early and advanced stages of the disease. The activity was assayed using the fluorogenic peptide substrate, Suc-Leu-Leu-Val-Tyr-AMC, in a cohort of 155 patients with early/advanced rectal (n=43/29), gastric (n=6/13), and breast (n=37/27) cancer and compared with that in normal individuals (n=55). The median plasma proteasome ChT-L activity was elevated by 20-32% in patients with advanced stage of rectal, gastric, and breast cancer compared with healthy donors. The difference turned out to be statistically significant (P<0.001). By contrast, values in patients with early stage of malignancies were not significantly different from those observed in normal individuals. We also found that plasma proteasome activity correlated with serum carcinoembryonic antigen levels in the group of patients with rectal cancer (r=0.433, P<0.05). Elevated plasma proteasome ChT-L activity is indicative of advanced stage of rectal, gastric, and breast cancer. However, the activity does not seem to be a parameter with clinically relevant potential in terms of early detection of cancer in this subset of patients.
authors: Department of Oncology, Medical University of Bialystok, Bialystok, Poland.
authors: Dominika
authors: D
authors: Hempel
authors: Marek Z
authors: MZ
authors: Wojtukiewicz
authors: Leszek
authors: L
authors: Kozłowski
authors: Jacek
authors: J
authors: Romatowski
authors: Halina
authors: H
authors: Ostrowska
references: Br J Dermatol. 2005 May;152(5):948-53
references: 15888151
references: Blood. 2007 Mar 1;109(5):2100-5
references: 17095627
references: Leuk Res. 2011 Apr;35(4):526-33
references: 20951430
references: Gut. 2009 Jun;58(6):833-8
references: 19201777
references: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10403-8
references: 10468620
references: J Immunol Methods. 2002 Feb 1;260(1-2):183-93
references: 11792388
references: Gynecol Oncol. 2011 Feb;120(2):233-8
references: 21075439
references: Nature. 1997 Apr 3;386(6624):463-71
references: 9087403
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Cancer. 2008 Mar 15;112(6):1306-12
references: 18224667
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Cancer. 2005 Nov 1;104(9):1794-807
references: 16178003
references: Eur Surg Res. 2007;39(4):245-50
references: 17457032
references: Chem Biol. 2001 Aug;8(8):739-58
references: 11514224
references: Annu Rev Biochem. 1996;65:801-47
references: 8811196
references: J Lab Clin Med. 1993 Feb;121(2):215-23
references: 8433038
references: Curr Opin Immunol. 2004 Feb;16(1):76-81
references: 14734113
references: Clin Cancer Res. 2009 Jun 1;15(11):3820-6
references: 19458051
references: Ann Surg Oncol. 2008 Dec;15(12):3433-9
references: 18846401
references: Front Biosci. 2008 May 01;13:4285-96
references: 18508511
references: Physiol Rev. 2002 Apr;82(2):373-428
references: 11917093
references: Cancer Invest. 2004;22(2):304-11
references: 15199612
references: Br J Haematol. 2006 Aug;134(3):253-62
references: 16787504
references: Clin Biochem. 2008 Nov;41(16-17):1377-83
references: 18773885
references: Blood. 2007 Nov 1;110(9):3281-90
references: 17591945
references: Exp Dermatol. 2010 Dec;19(12):1054-9
references: 20707810
references: Leukemia. 2002 Apr;16(4):433-43
references: 11960320
references: Cancer. 2001 Nov 15;92(10):2493-500
references: 11745181
references: FEBS Lett. 1988 Dec 5;241(1-2):239-45
references: 2461878
references: Arch Biochem Biophys. 2000 Nov 1;383(1):1-16
references: 11097171
references: Br J Haematol. 2007 Mar;136(6):814-28
references: 17341267
references: Nat Rev Cancer. 2004 May;4(5):349-60
references: 15122206
references: Annu Rev Pharmacol Toxicol. 2006;46:189-213
references: 16402903