Monica Davila

Assessment of Anti-Metastatic Effects of Anticoagulant and Antiplatelet Agents Using Animal Models of Experimental Lung Metastasis

It is well established that the blood coagulation system is activated in cancer. In addition, there is considerable evidence to suggest that clotting activation plays an important role in the biology of malignant tumors, including the process of blood-borne metastasis. For many years our laboratory has used experimental models of lung metastasis to study the events that follow the introduction of procoagulant-bearing tumor cells into circulating blood. This chapter focuses on the basic methods involved in assessing the anti-metastatic effects of anticoagulants and anti-platelet agents using rodent models of experimental metastasis. In addition, it summarizes our experience with these models, which collectively suggests that intravascular coagulation and platelet activation are a necessary prelude to lung tumor formation and that interruption of coagulation pathways or platelet aggregation may be an effective anti-metastatic strategy.

Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer

BACKGROUND Tissue factor (TF) is involved in tumor growth and metastasis and contributes to venous thromboembolism (VTE) in cancer, including gynecological malignancies. The diagnostic value of microvesicle-associated TF procoagulant activity (MV TF PCA) in women with suspected ovarian cancer, however, has not been studied. OBJECTIVE To evaluate MV TF PCA as a diagnostic tool in women with an ovarian mass of unknown etiology and as a predictive biomarker for perioperative VTE. METHODS Plasma MVs were isolated by high-speed centrifugation and analyzed for TF-specific PCA by single-stage clotting assay. In addition, plasma TF antigen and soluble P-selectin (sCD62P) were measured by ELISA. RESULTS D-Dimer, MV TF PCA, and sCD62P, but not the tumor marker, CA-125, significantly differentiated patients with malignant (n=40) from those with benign tumors (n=15) and healthy controls (n=34). In cancer patients, only D-Dimer and CA-125 correlated with the FIGO stage. An abnormal D-dimer had the highest sensitivity for the diagnosis of cancer, while MV TF PCA above the ROC curve-derived cut-off value of 182U/mL had the highest specificity. By multivariate logistic regression analysis, addition of MV TF PCA conferred diagnostic benefit to the single variables, CA-125 (p=0.052) and D-dimer (p=0.019). Perioperative VTE occurred in 16% of cancer patients and was associated with an advanced FIGO stage, but not MV TF PCA. There was no difference in plasma TF antigen levels between study groups. CONCLUSIONS MV TF PCA, but not plasma TF antigen, may provide valuable additional information for the diagnostic work-up of women with suspected ovarian cancer.

Corrigendum to ‘Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer”, [Thromb. Res. 141 (2016) 39–48]

a II. Medizinische Klinik und Poliklinik, Onkologisches Zentrum, Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Eppendorf, Martinistr 52, D-20246 Hamburg, Germany b Klinik und Poliklinik für Gynäkologie, Zentrum für Operative Medizin, Universitätsklinikum Eppendorf, Martinistr 52, D-20246 Hamburg, Germany c Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Eppendorf, Martinistr 52, D-20246 Hamburg, Germany d Florida Hospital Center for Thrombosis Research, 2566 Lee Road, Winter Park, FL 32789, USA e University of North Carolina at Chapel Hill, 111 Mason Farm Road, 2312B Medical Biomolecular Research Building, Campus, Box #7126, Chapel Hill, NC 27599, USA f Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München (LMU), Campus Großhadern und Innenstadt, Marchioninistr 15, 81377 München, Germany g K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway