INT104299

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Context Info
Confidence 0.47
First Reported 2002
Last Reported 2011
Negated 2
Speculated 0
Reported most in Body
Documents 18
Total Number 20
Disease Relevance 12.03
Pain Relevance 4.39

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

peptidase activity (Adam17) extracellular region (Adam17) cell motility (Adam17)
cell adhesion (Adam17) plasma membrane (Adam17) cytoplasm (Adam17)
Anatomy Link Frequency
liver 1
cleavage 1
extracellular matrix 1
A172 1
Adam17 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 423 99.36 Very High Very High Very High
fibrosis 418 99.28 Very High Very High Very High
Inflammatory response 61 99.20 Very High Very High Very High
metalloproteinase 384 99.08 Very High Very High Very High
cINOD 16 91.04 High High
cytokine 52 87.88 High High
Pain 14 72.48 Quite High
ischemia 15 66.64 Quite High
Bioavailability 11 66.48 Quite High
aspirin 2 60.40 Quite High
Disease Link Frequency Relevance Heat
Necrosis 143 100.00 Very High Very High Very High
Cancer 50 100.00 Very High Very High Very High
INFLAMMATION 468 99.36 Very High Very High Very High
Glioblastoma 2 99.32 Very High Very High Very High
Cirrhosis 165 99.28 Very High Very High Very High
Infection 30 99.16 Very High Very High Very High
Disease 278 98.80 Very High Very High Very High
Injury 513 98.76 Very High Very High Very High
Hepatitis 44 98.68 Very High Very High Very High
Liver Disease 44 97.68 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
release, inhibition of TACE by BB-94 was deemed irrelevant in their model; however, data was not shown [28].
Negative_regulation (inhibition) of TACE
1) Confidence 0.47 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.77 Pain Relevance 0.06
Inhibition of MMP and TACE activity with Marimastat during chronic CCl4 administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition.
Negative_regulation (Inhibition) of TACE associated with inflammation
2) Confidence 0.47 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2892485 Disease Relevance 0.81 Pain Relevance 0.20
Marimastat efficiently inhibits MMP-2, MMP-3, MMP-7, MMP-9, MMP-13 and TACE activity, with IC50s in the nM range [26], [54].
Negative_regulation (inhibits) of TACE
3) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.11 Pain Relevance 0.05
The ability of Marimastat to inhibit TACE activity prompted us to study the role of TNF-?
Negative_regulation (inhibit) of TACE
4) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.79 Pain Relevance 0.17
We confirmed that the broad-spectrum MMP-inhibitor Marimastat efficiently inhibited gelatinolytic and collagenolytic MMP, as well as TACE activities.
Negative_regulation (inhibited) of TACE
5) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.78 Pain Relevance 0.23
Diphenylamine-related compounds failed to down-regulate L-selectin in a tumor necrosis factor-alpha-converting enzyme (TACE)-deficient murine monocytic cell line.
Neg (failed) Negative_regulation (down-regulate) of TACE associated with necrosis and cancer
6) Confidence 0.37 Published 2002 Journal J. Biol. Chem. Section Abstract Doc Link 12147693 Disease Relevance 0.48 Pain Relevance 0.54
To further explore the anti-inflammatory and hepatoprotective potential of pharmacologic broad-spectrum MMP and TACE inhibition, C57Bl/6J mice were pretreated for 7 days with Marimastat and subsequently challenged with a single dose of CCl4.
Negative_regulation (inhibition) of TACE associated with inflammation
7) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.62 Pain Relevance 0.17
In conclusion, we demonstrate that broad-spectrum MMP- and TACE-activity inhibition with Marimastat during chronic CCl4 administration resulted in significantly attenuated hepatic inflammation and necrosis coupled with downregulation of genes related to fibrogenesis, but resulted in increased liver fibrosis.
Negative_regulation (inhibition) of TACE in liver associated with fibrosis, necrosis, cirrhosis and inflammation
8) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 1.19 Pain Relevance 0.42
Marimastat also inhibits TACE, with a suggested benefit in diseases that involve both inflammation and extracellular matrix remodeling [34].
Negative_regulation (inhibits) of TACE in extracellular matrix associated with inflammation and disease
9) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 0.93 Pain Relevance 0.54
Specific inhibition of TACE, however, may still be an attractive approach to manipulate the inflammatory cascade following a hepatic insult.


Negative_regulation (inhibition) of TACE associated with inflammation
10) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 1.02 Pain Relevance 0.39
0.05), likely reflecting pharmacologic inhibition of TACE and an ameliorated inflammatory response (Figure 2C) [22], [24].
Negative_regulation (inhibition) of TACE associated with inflammatory response
11) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 1.02 Pain Relevance 0.19
In our study, inflammation was significantly decreased by TACE inhibition while downregulation of TIMP-1 may have further improved hepatic regeneration, as reflected by the marked decrease in serum levels of alkaline phosphatase and ALT.
Negative_regulation (inhibition) of TACE associated with inflammation
12) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2892485 Disease Relevance 1.12 Pain Relevance 0.40
Diphenylamine-related compounds failed to down-regulate L-selectin in a tumor necrosis factor-alpha-converting enzyme (TACE)-deficient murine monocytic cell line.
Neg (failed) Negative_regulation (down-regulate) of factor-alpha-converting enzyme associated with necrosis and cancer
13) Confidence 0.32 Published 2002 Journal J. Biol. Chem. Section Abstract Doc Link 12147693 Disease Relevance 0.48 Pain Relevance 0.54
Additionally, an ADAM17 inhibitor prevented regulated ?
Negative_regulation (inhibitor) of ADAM17
14) Confidence 0.30 Published 2011 Journal Mol Brain Section Body Doc Link PMC3022812 Disease Relevance 0.22 Pain Relevance 0.08
-cleavage abolished in ADAM17-deficient cells, suggesting that ADAM17 is likely the ?
Negative_regulation (abolished) of ADAM17 in cleavage
15) Confidence 0.22 Published 2011 Journal Mol Brain Section Body Doc Link PMC3022812 Disease Relevance 0.24 Pain Relevance 0.08
In contrast Asai et al. [75] used short interfering RNAs (siRNAs) to deplete ADAM17 protein levels in human glioblastoma A172 cells and subsequently demonstrated that the proteinase was involved in both the constitutive and regulated endogenous ?
Negative_regulation (deplete) of ADAM17 protein in A172 associated with glioblastoma
16) Confidence 0.21 Published 2011 Journal Biochemistry Research International Section Body Doc Link PMC2989646 Disease Relevance 0.16 Pain Relevance 0
Similarly, the ADAM17 inhibitor, CP-661631, inhibited regulated but not constitutive sAPP?
Negative_regulation (inhibitor) of ADAM17
17) Confidence 0.21 Published 2011 Journal Biochemistry Research International Section Body Doc Link PMC2989646 Disease Relevance 0.44 Pain Relevance 0.11
converting enzyme, TACE) can be proteolytically cleaved to release its extracellular domain as soluble TGF-?
Negative_regulation (cleaved) of TACE
18) Confidence 0.19 Published 2011 Journal Mol Brain Section Body Doc Link PMC3022812 Disease Relevance 0.26 Pain Relevance 0.09
TACE inhibitors
Negative_regulation (inhibitors) of TACE
19) Confidence 0.13 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2577641 Disease Relevance 0.23 Pain Relevance 0.16
However, there were significant increases in the amount of shed MUC1 following knockdown of MMP-14 at 8 but not 24 h of infection, although no changes were seen following knockdown of ADAM17 (Figure 6D).
Negative_regulation (knockdown) of ADAM17 associated with infection
20) Confidence 0.08 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2752161 Disease Relevance 0.36 Pain Relevance 0

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