INT67884

Context Info Confidence 0.68 First Reported 1996 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 15 Total Number 17 Disease Relevance 11.21 Pain Relevance 2.61

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

Anatomy Link Frequency colon 1 PLAU (Homo sapiens)

Pain Link Frequency Relevance Heat palliative 12 99.10 metalloproteinase 52 96.44 Inflammation 23 90.12 cytokine 19 88.40 cINOD 13 86.88 methotrexate 6 85.64 Pain 9 80.84 Osteoarthritis 66 77.44 endometriosis 2 75.00 chemokine 2 71.96

Disease Link Frequency Relevance Heat Ovarian Cancer 23 99.78 Breast Cancer 230 99.70 Advanced Or Metastatic Breast Cancer 6 99.28 Cancer 372 99.20 Colon Cancer 8 99.04 Necrosis 3 98.44 Metastasis 139 98.32 Stress 9 97.52 Leukemia 1 95.16 Disease 50 93.04

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Nevertheless, in metastatic breast cancer, retrospective studies showed that elevated uPA or PAI-1 present in the primary tumor are associated with a poor response to later palliative endocrine therapy [14] suggesting that high levels of uPA and/or PAI-1 do reflect an aggressive phenotype that may be overcome by early systemic therapy in the adjuvant setting but not by palliative therapy at a later stage of the disease.

Positive_regulation (levels) of uPA associated with cancer, disease, advanced or metastatic breast cancer and palliative

1) Confidence 0.68 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.63 Pain Relevance 0.23

Nevertheless, in metastatic breast cancer, retrospective studies showed that elevated uPA or PAI-1 present in the primary tumor are associated with a poor response to later palliative endocrine therapy [14] suggesting that high levels of uPA and/or PAI-1 do reflect an aggressive phenotype that may be overcome by early systemic therapy in the adjuvant setting but not by palliative therapy at a later stage of the disease.

Positive_regulation (elevated) of uPA associated with cancer, disease, advanced or metastatic breast cancer and palliative

2) Confidence 0.49 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.86 Pain Relevance 0.23

However, despite attaining the of highest level of evidence for clinical application, uPA and PAI-1 are not widely used in clinical practice.

Neg (not) Positive_regulation (used) of uPA

3) Confidence 0.49 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.49 Pain Relevance 0.19

The measurement of uPA- and PAI-1-expression at the mRNA level using molecular biology techniques could thus constitute an alternative to the immunochemical assays currently being used.

Positive_regulation (measurement) of uPA

4) Confidence 0.49 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.52 Pain Relevance 0

Several recent analyses indicated that breast cancer patients with high uPA/PAI-1 protein levels derived a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1 contents [10,11].

Positive_regulation (high) of uPA associated with breast cancer

5) Confidence 0.49 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.89 Pain Relevance 0.04

Increased uPA messenger level was also associated with metastasis-free survival and breast cancer specific survival in univariate analysis, but did not represent a statistically significant independent prognostic factor.

Positive_regulation (Increased) of uPA associated with breast cancer and metastasis

6) Confidence 0.46 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1564186 Disease Relevance 0.99 Pain Relevance 0

ER stress markers such as glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and activating transcription factor (ATF)-3 were enhanced by sulindac sulfide in colon cancer cells.

Positive_regulation (enhanced) of ATF in colon associated with stress and colon cancer

7) Confidence 0.45 Published 2010 Journal Carcinogenesis Section Abstract Doc Link 20130018 Disease Relevance 1.20 Pain Relevance 0.49

Celecoxib caused phosphorylation of eukaryotic translation initiation factor 2 kinase (PERK) and eukaryotic initiation factor-2alpha (eIF2alpha) and production of activating transcription factor (ATF)4 mRNA.

Positive_regulation (activating) of ATF

8) Confidence 0.45 Published 2006 Journal Oncogene Section Abstract Doc Link 16205636 Disease Relevance 0.76 Pain Relevance 0.44

This may activate urokinase plasminogen activator (uPA) and gelatinase enzymes, which play a crucial role in trophoblast invasion.

Spec (may) Positive_regulation (activate) of uPA

9) Confidence 0.42 Published 2005 Journal Reprod. Biomed. Online Section Abstract Doc Link 16274610 Disease Relevance 0.40 Pain Relevance 0.14

Doses of unmicronized 1, 10 and 50 mg UPA exhibit proportional increases in peak serum levels, but serum levels from higher doses, 100 and 200 mg, are not dose-dependent, suggesting saturation of carrier sites.17

Positive_regulation (increases) of UPA

10) Confidence 0.35 Published 2010 Journal International Journal of Women's Health Section Body Doc Link PMC2971744 Disease Relevance 0.09 Pain Relevance 0.06

Pregnancy rates with LNG EC in the first 24 hours are approximately 1.5%, but increase to 2.6% during the period of 48 to 72 hours after exposure.7,9,11,12 Ulipristal acetate (UPA)

Positive_regulation (increase) of UPA

11) Confidence 0.32 Published 2010 Journal International Journal of Women's Health Section Body Doc Link PMC2971744 Disease Relevance 0.09 Pain Relevance 0

Indeed, elevated levels of uPA and PAI-1 are associated with poor clinical outcome in breast cancer and also have predictive value [33-35].

Positive_regulation (elevated) of uPA associated with breast cancer

12) Confidence 0.20 Published 2006 Journal Breast Cancer Res Section Body Doc Link PMC1779463 Disease Relevance 1.33 Pain Relevance 0.16

= tumor necrosis factor-alpha; TTBS 1× = Tris 20 mM, NaCl 150 mM (pH 7.5), and 0.1% Tween 20; uPA = urokinase plasminogen activator.

Positive_regulation (activator) of uPA associated with necrosis and cancer

13) Confidence 0.16 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246240 Disease Relevance 0.46 Pain Relevance 0.21

An excessive increase in the uPA system was shown to associate with tumour progression and metastasis formation [29-31], and an increase in MMPs is associated with degradation of ECM leading to the release of growth factors like bFGF and VEGF.

Positive_regulation (increase) of uPA associated with cancer and metastasis

14) Confidence 0.14 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2841144 Disease Relevance 1.23 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.

Positive_regulation (induction) of uPA associated with cancer, ovarian cancer and metalloproteinase

15) Confidence 0.09 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 0.81 Pain Relevance 0.23

They rose markedly after saruplase from 0.43 mg/l at 0 h to a maximum of 160 mg/l at 2 h, whereas the increase after urokinase (from 0.45 mg/l to 89.0 mg/l) was significantly smaller (P < 0.001).

Positive_regulation (increase) of urokinase

16) Confidence 0.05 Published 1996 Journal Blood Coagul. Fibrinolysis Section Abstract Doc Link 9034556 Disease Relevance 0.16 Pain Relevance 0.08

Plasmin is the main protease involved in (pro)-u-PA activation, which gives origin to the initiation of the classical protease cascade (plasmin, interstitial MMPs, MT1-MMP, Gelatinase A) leading to ECM degradation.

Positive_regulation (activation) of u-PA associated with metalloproteinase

17) Confidence 0.04 Published 2004 Journal Reprod Biol Endocrinol Section Body Doc Link PMC320496 Disease Relevance 0.30 Pain Relevance 0.07

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