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Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

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Tumor Biology

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.

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Abbreviations

ChT-L:

Chymotrypsin-like

Suc:

Succinyl

AMC:

7-Amino-4-methyl coumarin

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Acknowledgment

This work was supported by grants (nos. 3-25480F and 3-25578F) from the Medical University of Bialystok, Poland.

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Authors and Affiliations

  1. Department of Oncology, Medical University of Bialystok, Bialystok, Poland

    Dominika Hempel & Marek Z. Wojtukiewicz

  2. Department of Surgical Oncology, Ministry of Internal Affairs Hospital in Bialystok, Bialystok, Poland

    Leszek Kozłowski

  3. Department of Internal Diseases, Comprehensive Hospital in Bialystok, Bialystok, Poland

    Jacek Romatowski

  4. Department of Biology, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland

    Halina Ostrowska

Authors
  1. Dominika Hempel
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  2. Marek Z. Wojtukiewicz
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  3. Leszek Kozłowski
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  4. Jacek Romatowski
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  5. Halina Ostrowska
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Correspondence to Halina Ostrowska.

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Hempel, D., Wojtukiewicz, M.Z., Kozłowski, L. et al. Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors. Tumor Biol. 32, 753–759 (2011). https://doi.org/10.1007/s13277-011-0177-2

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  • DOI: https://doi.org/10.1007/s13277-011-0177-2

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