title: Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients.
abstract: Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 (p<0.001) and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma.
authors: Masaryk Memorial Cancer Institute, Faculty of Medicine Masaryk University Brno Zluty kopec, Brno, Czech Republic.
authors: J
authors: J
authors: Halamkova
authors: I
authors: I
authors: Kiss
authors: Z
authors: Z
authors: Pavlovsky
authors: J
authors: J
authors: Tomasek
authors: J
authors: J
authors: Jarkovsky
authors: Z
authors: Z
authors: Cech
authors: S
authors: S
authors: Tucek
authors: L
authors: L
authors: Hanakova
authors: M
authors: M
authors: Moulis
authors: J
authors: J
authors: Zavrelova
authors: M
authors: M
authors: Man
authors: P
authors: P
authors: Benda
authors: O
authors: O
authors: Robek
authors: Z
authors: Z
authors: Kala
authors: M
authors: M
authors: Penka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015996:Survival Rate; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator