INT113567

Context Info Confidence 0.79 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 12 Total Number 13 Disease Relevance 7.16 Pain Relevance 1.34

peptidase activity (PLAU) signal transduction (PLAU) extracellular space (PLAU) extracellular region (PLAU) plasma membrane (PLAU)

Anatomy Link Frequency PC-3 2 endothelial cells 1 PLAU (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 47 99.40 aspirin 27 98.94 cINOD 7 94.32 headache 3 68.76 abdominal pain 2 67.88 antagonist 35 66.16 COX-2 inhibitor 6 57.68 withdrawal 1 18.28 cytokine 12 5.00 Pain 8 5.00

Disease Link Frequency Relevance Heat Cancer 266 99.84 Adhesions 94 99.60 Malignant Neoplastic Disease 23 99.10 Prostate Cancer 187 98.72 Ovarian Cancer 23 98.30 Breast Cancer 82 98.12 Carcinoma 21 97.44 Pancreatic Cancer 3 96.80 INFLAMMATION 7 92.96 Metastasis 127 81.40

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Previous studies focused on messengers of the components of the plasminogen activation system in human breast cancer by mainly comparing normal, benign and malignant breast tissues or by examining the cellular localization of uPA and PAI-1 [25-30].

Localization (localization) of uPA associated with malignant neoplastic disease and breast cancer

1) Confidence 0.79 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.69 Pain Relevance 0

We have recently demonstrated that constitutively active nuclear factor-kappa B (NF-kappaB) is responsible for the increased secretion of uPA and that inhibition of NF-kappaB suppresses secretion of uPA and cell migration of highly invasive cancer cells.

Localization (secretion) of uPA associated with cancer

2) Confidence 0.76 Published 2003 Journal Int. J. Oncol. Section Abstract Doc Link 14532966 Disease Relevance 0.96 Pain Relevance 0.29

We have recently demonstrated that constitutively active nuclear factor-kappa B (NF-kappaB) is responsible for the increased secretion of uPA and that inhibition of NF-kappaB suppresses secretion of uPA and cell migration of highly invasive cancer cells.

Localization (secretion) of uPA associated with cancer

3) Confidence 0.76 Published 2003 Journal Int. J. Oncol. Section Abstract Doc Link 14532966 Disease Relevance 0.95 Pain Relevance 0.27

Here we show that aspirin inhibits NF-kappaB, resulting in the suppression of uPA secretion from the highly invasive human prostate cancer cells PC-3.

Localization (secretion) of uPA in PC-3 associated with aspirin and prostate cancer

4) Confidence 0.76 Published 2003 Journal Int. J. Oncol. Section Abstract Doc Link 14532966 Disease Relevance 1.05 Pain Relevance 0.35

ELISA showed the inhibitions of u-PA secretion in chondral cultures by diclofenac and rofecoxib as well as in chondral and synovial cultures by nimesulide, celecoxib and etoricoxib at 48 h.

Localization (secretion) of u-PA

5) Confidence 0.75 Published 2008 Journal Clin. Biochem. Section Body Doc Link 17996201 Disease Relevance 0.08 Pain Relevance 0

Unfortunately, immunohistochemical assays of the uPA/PAI-1 system have provided unsatisfactory results mainly due to an absence of consensus regarding uPA and PAI-1 cellular localization [24].

Localization (localization) of uPA

6) Confidence 0.69 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.58 Pain Relevance 0

So far it is unknown whether UPA is excreted in human milk as studies are lacking.

Localization (excreted) of UPA

7) Confidence 0.56 Published 2010 Journal International Journal of Women's Health Section Body Doc Link PMC2971744 Disease Relevance 0.20 Pain Relevance 0.14

Efficacy of UPA

Localization (Efficacy) of UPA

8) Confidence 0.52 Published 2010 Journal International Journal of Women's Health Section Body Doc Link PMC2971744 Disease Relevance 0 Pain Relevance 0

COX-2, MMPs, and uPA-system inhibition impacts on neo-angiogenic potential of tumour cells

Localization (potential) of uPA associated with cancer

9) Confidence 0.23 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2841144 Disease Relevance 0.60 Pain Relevance 0.03

In the ovarian carcinoma cells, co-induction of uPA system, by the concomitant stimulation of production and secretion of uPA and uPAR, and MMPs by ET-1 resulted into the highest invasive potential of tumor cells through the Matrigel.

Localization (secretion) of uPA associated with cancer, ovarian cancer and metalloproteinase

10) Confidence 0.13 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 0.82 Pain Relevance 0.23

PC-3 and C4-2 secrete more u-PA than LNCaP cells [116,117], which is most notably involved in the regulation of ECM-laminin degradation, thereby allowing for PC-3 and C4-2 cells to behave more aggressively.

Localization (secrete) of u-PA in PC-3

11) Confidence 0.06 Published 2004 Journal Reprod Biol Endocrinol Section Body Doc Link PMC320496 Disease Relevance 0.23 Pain Relevance 0.03

They found that differential production of u-PA corresponded with the ability of the more aggressive lines to bind and activate plasminogen; thus providing direct support that u-PA secretion and the levels of u-PA- u-PAR complexes characterize the invasive phenotype of these cells [118].

Localization (secretion) of u-PA

12) Confidence 0.06 Published 2004 Journal Reprod Biol Endocrinol Section Body Doc Link PMC320496 Disease Relevance 0.39 Pain Relevance 0

These two proteins interact and the Somatomedin B domain and helps in the localization of uPA to focal adhesions in microvessel endothelial cells.

Localization (localization) of uPA in endothelial cells associated with adhesions

13) Confidence 0.05 Published 2008 Journal BMC Evol Biol Section Body Doc Link PMC2246102 Disease Relevance 0.60 Pain Relevance 0

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