INT321560

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Context Info
Confidence 0.46
First Reported 2010
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 14
Total Number 30
Disease Relevance 13.02
Pain Relevance 0.03

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular region (Plaur) plasma membrane (Plaur) enzyme binding (Plaur)
kinase activity (Plaur)
Anatomy Link Frequency
extracellular matrix 1
Plaur (Mus musculus)
Pain Link Frequency Relevance Heat
Inward rectifier potassium channel 13 67.76 Quite High
metalloproteinase 52 36.76 Quite Low
cINOD 17 36.36 Quite Low
potassium channel 13 5.00 Very Low Very Low Very Low
Central nervous system 13 5.00 Very Low Very Low Very Low
anesthesia 13 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Glioma 871 99.84 Very High Very High Very High
Adhesions 398 99.60 Very High Very High Very High
Cancer 1089 99.20 Very High Very High Very High
Apoptosis 179 98.56 Very High Very High Very High
Malignant Neoplastic Disease 65 97.92 Very High Very High Very High
Metastasis 73 97.04 Very High Very High Very High
Colon Cancer 34 97.04 Very High Very High Very High
Lung Cancer 17 95.80 Very High Very High Very High
Skin Cancer 17 91.44 High High
Wound Healing 78 91.20 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
MMP-9, uPAR and cathepsin B downregulation significantly inhibits xenograft cell adhesion to several extracellular matrix proteins.
Negative_regulation (downregulation) of uPAR in extracellular matrix associated with adhesions
1) Confidence 0.46 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2904700 Disease Relevance 0.58 Pain Relevance 0
Reduction in the mRNA levels of MMP-9, uPAR and cathepsin B in M-sh, U-sh and C-sh transfected 4910 cells indicated a downregulation of MMP-9, uPAR and cathespin B target mRNAs, the mechanism by which shRNAs are proposed to work [24], [25].
Negative_regulation (downregulation) of uPAR
2) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.26 Pain Relevance 0
In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential.


Negative_regulation (downregulated) of uPAR associated with adhesions and glioma
3) Confidence 0.46 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2904700 Disease Relevance 0.62 Pain Relevance 0
As expected, inhibition of adhesion of these cells to ECM components is much more significant with the simultaneous downregulation of MMP-9 and uPAR or MMP-9 and cathepsin B.
Negative_regulation (downregulation) of uPAR associated with adhesions
4) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 1.41 Pain Relevance 0
Bicistronic constructs that can simultaneously downregulate MMP-9 and uPAR or MMP-9 and cathepsin B were more effective than any of the single constructs.
Negative_regulation (downregulate) of uPAR
5) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.36 Pain Relevance 0
Reduction in the mRNA levels of MMP-9, uPAR and cathepsin B in M-sh, U-sh and C-sh transfected 4910 cells indicated a downregulation of MMP-9, uPAR and cathespin B target mRNAs, the mechanism by which shRNAs are proposed to work [24], [25].
Negative_regulation (Reduction) of uPAR
6) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.18 Pain Relevance 0
Hence, in the present study, we investigated the effect of downregulating MMP-9, uPAR and ctahepsin B using both single as well as MMP-9/uPAR and MMP-9/cathepsin B bicistronic shRNA plasmid constructs on the expression of integrins and on the migrating and invasive potential of glioma xenograft cells.


Negative_regulation (downregulating) of uPAR associated with glioma
7) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.44 Pain Relevance 0
Downregulation of proteases and uPAR inhibits adhesion to ECM proteins
Negative_regulation (Downregulation) of uPAR associated with adhesions
8) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.42 Pain Relevance 0
Simultaneous downregulation of MMP-9 along with either uPAR or cathepsin B reduced the invasive potential of 4910 and 5310 cells through the Matrigel (Fig. 5E).
Negative_regulation (downregulation) of uPAR
9) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.45 Pain Relevance 0
In this study, downregulation of uPAR and the proteases, MMP-9 and cathepsin B showed a significant reduction in the adhesion, migration and invasive potential of xenografts and also affected the levels of several alpha and beta integrins.
Negative_regulation (downregulation) of uPAR associated with adhesions
10) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.58 Pain Relevance 0.03
Yu [65] has reported that the downregulation of uPAR induced G0/G1 arrest in vitro but did not affect growth in vivo.
Negative_regulation (downregulation) of uPAR
11) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 1.00 Pain Relevance 0
The effect of RNAi-mediated inhibition of cathepsin B and uPAR on pre-established tumors was studied.
Negative_regulation (inhibition) of uPAR associated with cancer
12) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.59 Pain Relevance 0
Similarly, the present study demonstrates that the simultaneous downregulation of cathepsin B and uPAR caused the regression of intracranial tumors.
Negative_regulation (downregulation) of uPAR associated with cancer
13) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.76 Pain Relevance 0
Here, we show that shRNA-mediated downregulation of cathepsin B and uPAR results in G0/G1 arrest, prominent increased expression of p27Kip1 and inhibition of p-Rb.
Negative_regulation (downregulation) of uPAR
14) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.24 Pain Relevance 0
Since we observed p27Kip1 upregulation with decreased cell proliferation and G0/G1 phase arrest with the depletion of cathepsin B and uPAR, we next determined the expression of FOXO proteins, which are important transcriptional regulators of the p27Kip1 promoter.
Negative_regulation (depletion) of uPAR
15) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0 Pain Relevance 0
We have previously shown that RNAi-mediated downregulation of cathepsin B and uPAR led to decreased invasion, induction of angiogenesis, increased caspase-mediated apoptosis, and induction of G0/G1 arrest [2], [30], [33]–[37] Data from other reports indicate that inhibition or depletion of cathepsin B prevents cells from entering and leaving the cell cycle, thereby decreasing cell proliferation [38], [39].
Negative_regulation (downregulation) of uPAR associated with apoptosis
16) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.71 Pain Relevance 0
In an attempt to elucidate the roles of cathepsin B and uPAR in cell cycle progression, we analyzed the activity of crucial regulators of the G0/G1 transition including p27Kip1 by downregulating cathepsin B and uPAR both individually and simultaneously in SNB19 and U251 glioma cells.
Negative_regulation (downregulating) of uPAR associated with glioma
17) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.36 Pain Relevance 0
Cathepsin B and uPAR depletion affects the p27Kip1 expression and its subcellular localization
Negative_regulation (depletion) of uPAR
18) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.10 Pain Relevance 0
To test whether the depletion of uPAR and/or cathepsin B affected localization of the FOXO3a protein, cytosolic and nuclear fractions were immunoblotted for FOXO3a.
Spec (whether) Negative_regulation (depletion) of uPAR
19) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0 Pain Relevance 0
To further confirm the role of p27Kip1 in growth arrest induced by the depletion of cathepsin B and uPAR, we knocked down the expression of p27Kip1 alone or in combination with uPAR and/or cathepsin B, and we analyzed cell proliferation using BrdU incorporation assay.
Negative_regulation (depletion) of uPAR
20) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0 Pain Relevance 0

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