Profiles of plasma serpins in patients with advanced malignant melanoma, gastric cancer and breast cancer.
ABSTRACT Blood coagulation and fibrinolysis are activated systemically in patients with malignancy. The precarious balance between coagulation and fibrinolysis is modulated by serine proteinase inhibitors (serpins). Levels of selected serpins (alpha1-antichymotrypsin, alpha1-antitrypsin, alpha2-macroglobulin, antithrombin III, C1 inhibitor, alpha2-antiplasmin), substrates (factor XIIIa, fibrinogen, fibronectin) and endproducts (fibrin/fibrinogen degradation products) of coagulation reactions were measured in the plasma of 61 patients with common malignancies associated with a tendency to thrombosis (i.e. malignant melanoma, gastric cancer and breast cancer). The data revealed a heterogeneity in plasma levels of serpins between tumor types. The most profound differences between cancer and healthy subject groups were found in breast cancer patients. Levels of alpha1-antitrypsin were significantly higher and levels of alpha2-antiplasmin were significantly lower in all cancer groups, whereas there were no differences in antithrombin III levels.
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ABSTRACT: Malignancy is associated with alterations in the hemostatic system that present as thromboembolic or bleeding complications. Antineoplastic treatment further escalates blood coagulation and fibrinolytic abnormalities. Moreover, hemostatic system inhibitors play a role in tissue maintenance or, contrarily, contribute to cancer progression. The inhibitors regulate migration, proliferation, apoptosis, angiogenesis, and distant metastases formation, as well as interfere with host defense system mechanisms. They exhibit different functions depending on tumor type, histologic grade, and clinical stage of the disease. The activity of coagulation inhibitors underlies the pathomechanisms of some complications resulting from therapeutic procedures, such as radiation injury to normal tissues. Because coagulation activation is widely recognized to influence cancer growth and distant dissemination, numerous attempts were made to introduce various forms of coagulation inhibitors to antineoplastic treatment. This review summarizes up-to-date information on preclinical and clinical benefits and pitfalls of hemostatic system inhibitors administration in cancer, with special emphasis on tumor biology and prophylaxis and treatment of various complications observed in the course of malignant disease.Seminars in Thrombosis and Hemostasis 11/2007; 33(7):621-42. · 4.52 Impact Factor
Article: Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry.[show abstract] [hide abstract]
ABSTRACT: Screening mammography is the most effective tool available for breast cancer detection. While screening mammography saves lives, it has intrinsic problems that limit further improvement. We hypothesize that protein biomarkers in nipple aspirate fluid (NAF) may separate the cancer from the non-cancer state, and therefore can be used for breast cancer detection. In this study the proteins in NAF were analyzed by surface-enhanced laser desorption ionization coupled to time-of-flight mass spectrometry (SELDI-TOF) in the m/z 5,000-85,000 range. Two methods were used to normalize spectra. Then differentially expressed signals that separate cancer from non-cancer conditions were selected by two specifically developed statistical algorithms. Proteins of interest were identified by combined liquid chromatography-tandem mass spectrometry. A set of 8 markers were identified which collectively gave 63% sensitivity, 89% specificity and 76% accuracy for distinguishing cancer from non-cancer. Further improvements in the specificity and sensitivity of this strategy could come from the development of methods for more precise quantification of the biomarkers of interest and also from focusing on the low abundant components that are not evident when unfractionated NAF is analyzed directly.International Journal of Oncology 02/2007; 30(1):145-54. · 2.40 Impact Factor