Biomedical subjects

M Z Wojtukiewicz

Publications and source records attributed to M Z Wojtukiewicz.

43 records · Page 3Linked to original sources

PubMedDate not supplied

Clotting factors in tumour tissue: implications for cancer therapy.

Considerable progress has been made recently in understanding the mechanisms and significance of coagulation activation in human malignancy. Neoplastic cells may activate coagulation reactions directly, that is through contact with coagulation factors; or indirectly by formation of cytokines capable of activating certain host cells such as macrophages or endothelial cells. Data suggest that at least two autoregulatory pathways involving components of coagulation and fibrinolysis pathways exist. In one of these, tumour cell procoagulants lead to generation of thrombin in the tumour periphery. Thrombin is a mitogen that may also contribute to tumour stoma formation. Alternatively, tumour cells may express urokinase responsible for generation of cell surface-related proteolysis that may facilitate tumour cell proliferation, invasion and metastasis. An appreciation of these diverse mechanisms may permit rational design of clinical trials of agents capable of interrupting relevant pathways.

Anticoagulants↗

PubMedDate not supplied

Profiles of plasma serpins in patients with advanced malignant melanoma, gastric cancer and breast cancer.

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.

Aged↗

PubMedDate not supplied

Effects of polysulfonate derivative (GL 522-Y-1) on coagulation in vitro and thrombosis in vivo.

We have investigated the influence of a polysulfonate derivative - GL 522-Y-1 - on platelet-induced thrombin generation time, platelet adhesion to siliconized glass, platelet aggregation induced by collagen and ADP, on aPTT, PT and TT in vitro and studied its antithrombotic effect in an animal model of thrombosis in vivo. In vitro, GL 522-Y-1 caused inhibition of ADP- and collagen-induced aggregation. In a dose-dependent manner this compound inhibited PITT, aPTT, and PT. GL 522-Y-1 did not prolong thrombin time. GL 522-Y-1 inhibited in vivo the laser-induced thrombus formation after intravenous and oral administration. On the basis of its unique antithrombotic properties, GL 522-Y-1 seems to open a new pathway in the field of antithrombotics.

Animals↗

PubMedDate not supplied

Lactacystin inhibits cathepsin A activity in melanoma cell lines.

We describe the inhibitory effect of the proteasome inhibitor, lactacystin, on cathepsin A activity in murine melanoma cell lines. In vitro lactacystin metabolite, beta-lactone, at a concentration of 1 microM, significantly suppressed cathepsin A activity in B78 melanoma cell lysates by about 50%. Exposure of three murine melanoma cell lines with different metastatic potential to lactacystin at a concentration of 5 microM for 6 h caused a significant reduction in the carboxypeptidase activity of this enzyme, while the inhibitory activity remained unchanged for at least 12 h. Other proteasome-specific inhibitors, e.g. epoxomicin and N-benzyloxycarbonyl-Ile-Glu(O-tert-Bu)-Ala-leucinal (PSI) at a concentration of 1 microM did not affect cathepsin A activity in melanoma cell line lysates. These data support our previous proposal that lactacystin is not a specific inhibitor of the proteasome. Since cathepsin A is also a tumor-associated enzyme, further research is needed to clarify its role and the significance of its inhibition by lactacystin in tumor biology.

Acetylcysteine↗

PubMedDate not supplied

Fibrinogen-fibrin transformation in situ in renal cell carcinoma.

The mechanism of coagulation activation in renal cell carcinoma was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary tumors. Tissue factor antigen was detected in the endothelium of vascular channels within the tumors. Fibrinogen and factor V were distributed diffusely in the perivascular tumor connective tissue. Fibrin was readily detected in a linear pattern along the edges of nodules of viable tumor indicating that thrombin had formed from the interaction of coagulation factors demonstrated previously in renal cell carcinoma tissue. Tissue plasminogen activator was detected in the endothelium of blood vessels in the vicinity of the tumor and urokinase in areas of necrosis but neither were associated with viable tumor cells. These results indicate that thrombin is formed locally in renal cell carcinoma tissue that transforms fibrinogen to fibrin. There also appears to be a net deficit in fibrinolysis in situ in this tumor. We postulate that these conditions might contribute to stabilization and progression of renal cell carcinoma and that clinical trials of antithrombotic agents are justified in this tumor type.

Antibodies↗

PubMedDate not supplied

Immunohistochemical demonstration of fibrin II in gastric cancer tissue.

Immunohistochemistry was applied to AMeX-fixed sections of twelve cases of gastric carcinoma obtained at surgical resection to explore the occurrence and distribution of fibrin deposits in situ. Fibrinogen was distributed in abundance throughout perivascular zones and in the connective tissue of the tumor stroma. Fibrin II (des-fibrinopeptide B-type fibrin) was easily identified in a direct apposition to the surface membranes of viable carcinoma cells, predominantly at the host-tumor interface and in the regions immediately adjacent to the zones of angiogenesis. Further studies are required to identify the triggers of the coagulation reactions as well as fibrinolytic system components in the gastric cancer tissue.

Carcinoma↗

PubMedDate not supplied

Prothrombin activation fragment 1 + 2 and thrombin-antithrombin-III complexes in plasma of patients with essential arterial hypertension.

Prothrombin activation fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III complexes (TAT) were measured in plasma of 34 patients with newly diagnosed essential hypertension. The patients with hypertension showed an increase in both F1 + 2 and TAT concentrations. The obtained results point to the intravascular thrombin generation in very early stages of essential hypertension.

Adult↗