Gene/Protein
Disease
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Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P00750 (
PLA
)
16,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We quantitated urokinase and tissue plasminogen activator (u-PA,
t-PA
), plasminogen activator inhibitor 1 and 2 (PAI-1, PAI-2), and fibrinolytic activity in peripheral blood (PB), tumour blood (TB), peritoneal/ascitic fluid (PAF) and cystic fluid (CF) from 104 patients with benign and 36 patients with malignant ovarian tumours, and in peripheral blood from 62 healthy controls. PB levels of u-PA were higher in patients with benign and malignant tumours than in controls. High concentrations of u-PA were found in CF, but not in TB, suggesting that u-PA is released by the tumour tissue, but not by the tumour vasculature. PB levels of
t-PA
were higher in both tumour groups than in controls. Increased levels of
t-PA
were found in TB, but not in CF, indicating that
t-PA
is released by the tumour vasculature, but not by the tumour tissue. PB levels of PAI-1 were higher in patients with both benign and malignant tumours than in controls. High levels of PAI-1 were present in both TB and CF from malignant tumours, suggesting that PAI-1 is released from the tumour vasculature as well as the tumour tissue. Elevated concentrations of PAI-2 were found in CF, but not in TB, indicating release from the tumour tissue, but not from the vasculature. High levels of
t-PA
, PAI-1 and PAI-2 were found in PAF of malignant tumours, and resorption from this compartment may explain elevated PB levels in patients with ascites. None of the PAs/PAIs proved useful as a PB marker for detection of early stage ovarian cancer. However, an index based on PAF levels of
t-PA
and PAI-1 discriminated between malignant and benign
ovarian cysts
in the absence of ascites. In addition, our study stresses the importance of including patients with benign tumours as well as healthy controls when markers for malignant tumours are evaluated.
...
PMID:Plasminogen activators and plasminogen activator inhibitors in blood and tumour fluids of patients with ovarian cancer. 799 18
In many tumor types, angiogenesis is the net result of pro- and anti-angiogenic mediators and correlated with metabolic activity, growth, and degree of malignancy. One of the first discovered anti-angiogenic compounds is angiostatin, a proteolytic fragment of plasminogen. The requirements for in vivo angiostatin generation have not yet been determined. We investigated the levels of plasminogen and angiostatin by western blotting and of components of the
plasminogen activator
complex by ELISA in cyst fluid derived from benign and malignant ovarian tumors. Fluid samples from functional ovarian follicles, dermoid cysts and endometriotic lesions were evaluated separately. When no or minimal amounts of plasminogen were present in the cyst fluids, angiostatin was generally absent as well, irrespective of
plasminogen activator
concentrations. When plasminogen was present, the degree of conversion of plasminogen to angiostatin was significantly correlated with the level of uPA, and, to a lesser extent, to the tPA level. However, angiostatin was also found in a number of cyst fluid samples with minimal or no plasminogen activators, suggesting the involvement of other angiostatin generating proteases in these samples. Conversely, no angiostatin was observed in a number of cyst fluid samples containing both plasminogen and plasminogen activators. The presence of an inhibitor of the enzymatic activity of uPA and/or tPA, like PAI-1, may explain this finding. Our data show that plasminogen activators are clearly involved in in vivo angiostatin formation in
ovarian cysts
. Most likely, however, other proteases, as well as inhibitors of plasminogen activators, are involved as well.
...
PMID:Plasminogen activators are involved in angiostatin generation in vivo in benign and malignant ovarian tumor cyst fluids. 2453 12