The biochemistry and physiology of urokinase

Celander, D. R.; Guest, M. Mason

doi:10.1016/0002-9149(60)90333-7

Cited by 59 publications

(19 citation statements)

References 14 publications

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“…Plasma activator is believed to originate from cells of blood vessels and can be released in blood in vivo after various stimuli (4)(5)(6)(7)(8). Ac-tivator in urine, urokinase (UK), is produced by kidney cells (9) but may also be derived from other sources (10,11). Urokinase, tissue, and plasma activators differ from each other immunologically (8) and in other properties (3,12).…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study

Bernik¹,

Kwaan

1969

J. Clin. Invest.

127

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Section: Introductionmentioning

confidence: 99%

Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study

Bernik¹,

Kwaan

1969

J. Clin. Invest.

127

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“…Further characterization of the two endogenous plasminogen activators was made by a num ber of different groups. [23][24][25][26][27][28][29][30] Techniques for purification of urokinase in appreciable quantities led to its introduction as a therapeutic alternative to streptokinase. [31][32][33][34][35][36][37][38][39] Though delayed by initial difficulties in isolation and purification, recombinant tissue plasminogen activator is now pro duced in large quantities through the use of recombinant molecular biologic techniques.…”

mentioning

confidence: 99%

The Fibrinolytic System in Neoplasia

Bell¹

1996

Semin Thromb Hemost

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During activation of the fibrinolytic system plasminogen is converted to plasmin by tissue plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA is predominantly released from endothelial cells, u-PA primarily by renal parenchymal cells. The activation of plasminogen is regulated by plasminogen activator inhibitor-1 (PAI-1), plasmin is controlled by alpha 2-plasmin inhibitor. The fibrinolytic system is not only involved in the intravascular dissolution of fibrin (thrombi), it also plays a vital role in normal physiologic reproduction, wound repair, angiogenesis, and tissue remodeling. Fibrinolysis is also a vital component in the pathogenesis of neoplastic disease. It is essential in releasing cells from their primary site of origin, providing nutrition for neoplastic cell growth and promoting cell mobility and motility. In neoplastic cells the degradation of the extracellular matrix proteins is facilitated by excessive expression of u-PA, t-PA, and u-PAR. In many forms of carcinoma increased expression of u-PAR and u-PA is associated with significantly shorter survival. Greater expression of u-PA in breast cancer cells, for example, is associated with shorter survival and increased relapse rate. Progressively aggressive neoplastic cells evidence high expression of u-PA and u-PAR activities, variable expression of t-PA, and enhanced PAI-1 and PAI-2 activities. In acute nonlymphocytic leukemias, poor outcome correlates with high t-PA levels. In acute progranulocytic leukemia there is a high incidence of DIC. Neoplastic prostatic tissue also expresses high u-PA activity and the more aggressive the cell line, the greater the number of u-PAR and the higher the u-PA activity. In gynecologic malignancies, a greater expression of u-PA in combination with cathepsin D is associated with widespread disease and poor prognosis. High u-PA values were also seen in patients with brain, gastric, and hepatic malignancies. It is evident that the plasminogen-plasmin system is a vital component in the biology of neoplastic disease and that it is, in theses conditions, in no way beneficial to the host.

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“…The other form of inhibition against plasminogen activation to be found in whole blood is due to the presence of antibodies developed as a result of stimulation by heterologous protein antigens: the most important of these in humans is the anti-streptokinase antibody resulting from incidental streptococcal infections. The urokinase used so far has always been of human origin and anti-urokinase antibodies have not been reported in man, although human urokinase is probably antigenic to other species (Celander and Guest, 1960). The inhibitory effect of antibodies is not influenced by those factors governing the production of the blood anti-activator but is present in the circulating blood: by varying the conditions of collection of the blood sample it is therefore possible to assay the inhibitory effect of antibody alone or the total inhibition due to antibody plus blood inhibitor.…”

Section: Anti-activator Assay Inhibition Of Plasminogenmentioning

confidence: 99%

A standard clot method for the assay of plasminogen activators, anti-activators, and plasmin

Hawkey

Stafford

1964

Journal of Clinical Pathology

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(Christensen, 1949; Johnson and Tillett, 1952; Fletcher, 1954;Baumgarten, Ciminera, and Cole, 1960). The purpose of this communication is the detailed description of a method found to be suitable for general laboratory use, incorporating reagents readily available in Europe: the results obtained during standardization are recorded and the selected commercial preparations specified.The standard clot comprises fibrinogen and thrombin, to which plasminogen and activator may be added if appropriate. It is made up to a fixed volume with buffer and thus provides 'reagent' space so that the components to be tested are actually included in the fibrin clot and their intrinsic effect on the subsequent lysis time can be measured. The method depends on the fibrin clot so formed being reproducible, stable, of constant volume, and uniformly susceptible to the action of plasmin. It offers a number of advantages over others in current use. The selection of fibrin as the substrate more nearly reproduces physiological conditions than does that of casein or the synthetic esters. It is shorter and easier to use quantitatively than the fibrin plate method (Astrup and Mullertz, 1952) which has the further disadvantage that the test substance cannot actually be incorporated in the

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The biochemistry and physiology of urokinase

Cited by 59 publications

References 14 publications

Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study

Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study

The Fibrinolytic System in Neoplasia

A standard clot method for the assay of plasminogen activators, anti-activators, and plasmin

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