INT70437

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Context Info
Confidence 0.57
First Reported 1997
Last Reported 2010
Negated 2
Speculated 1
Reported most in Body
Documents 115
Total Number 117
Disease Relevance 41.03
Pain Relevance 35.72

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

cell differentiation (Mdk) extracellular region (Mdk)
Anatomy Link Frequency
neuronal 6
neurons 4
spinal 2
lung 2
microglia 2
Mdk (Mus musculus)
Pain Link Frequency Relevance Heat
Neuropathic pain 115 99.96 Very High Very High Very High
nMDA receptor 224 99.92 Very High Very High Very High
intrathecal 109 99.76 Very High Very High Very High
Anterior cingulate cortex 308 99.72 Very High Very High Very High
Eae 134 99.68 Very High Very High Very High
long-term potentiation 988 99.64 Very High Very High Very High
Immobilon 7 99.56 Very High Very High Very High
antagonist 150 99.50 Very High Very High Very High
Kinase C inhibitor 4 99.40 Very High Very High Very High
Inflammation 496 99.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Neuropathic Pain 218 99.96 Very High Very High Very High
Toxicity 96 99.92 Very High Very High Very High
Inflammatory Pain 100 99.68 Very High Very High Very High
Reprotox - General 1 101 99.64 Very High Very High Very High
Cognitive Disorder 69 99.58 Very High Very High Very High
Cancer 909 99.48 Very High Very High Very High
Nociception 280 99.48 Very High Very High Very High
INFLAMMATION 471 99.24 Very High Very High Very High
Hepatocellular Cancer 39 99.20 Very High Very High Very High
Bacillus Anthracis Infection 13 99.20 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
To study the importance of ERKs in nociception, most studies mentioned above have utilized intrathecal pharmacological inhibition of MEK using either PD 98059 or U0126, which may inhibit MEK function in both neuronal and non-neuronal cells.
Negative_regulation (inhibition) of MEK in neuronal associated with nociception and intrathecal
1) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.71 Pain Relevance 0.85
To study the importance of ERKs in nociception, most studies mentioned above have utilized intrathecal pharmacological inhibition of MEK using either PD 98059 or U0126, which may inhibit MEK function in both neuronal and non-neuronal cells.
Negative_regulation (inhibit) of MEK in neuronal associated with nociception and intrathecal
2) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.75 Pain Relevance 0.86
In the present study, we investigated the effects of reduced neuronal MEK function in the DN MEK mice in the formalin test.
Spec (investigated) Negative_regulation (reduced) of MEK in neuronal
3) Confidence 0.57 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.60 Pain Relevance 0.51
To address the above concerns, and to evaluate the specific contribution of neuronal ERK activation to pain behavior, we aimed to test whether selective suppression of neuronal MEK activity can decrease nociceptive plasticity using the formalin model.
Negative_regulation (suppression) of MEK in neuronal associated with nociception, pain and eae
4) Confidence 0.42 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.52 Pain Relevance 0.54
Our data are also in agreement with a wealth of previous data reporting that MEK inhibitors reduce inflammatory pain using different pain models in rodents [6,29,30].
Negative_regulation (inhibitors) of MEK associated with pain and eae
5) Confidence 0.42 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.28 Pain Relevance 0.26
Dominant negative MEK (DN MEK) mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain.


Negative_regulation (suppressed) of MEK in neurons associated with eae
6) Confidence 0.42 Published 2006 Journal Mol Pain Section Abstract Doc Link PMC1382249 Disease Relevance 0.70 Pain Relevance 0.56
These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells.
Negative_regulation (inhibition) of MEK in neuronal associated with pain
7) Confidence 0.42 Published 2006 Journal Mol Pain Section Abstract Doc Link PMC1382249 Disease Relevance 0.62 Pain Relevance 0.44
MEK inhibition is a prime target for melanoma therapy given BRAF's downstream dependence on MEK for signal propagation [Figure 1].
Negative_regulation (inhibition) of MEK associated with addiction and skin cancer
8) Confidence 0.42 Published 2010 Journal Journal of Carcinogenesis Section Body Doc Link PMC2862505 Disease Relevance 0.63 Pain Relevance 0.05
Recently, melanoma cell lines harboring BRAF mutations were found to be markedly more sensitive to MEK inhibition than lines with NRAS mutations.[436] GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.[44] The objective response rate, safety, and pharmacokinetics of GSK1120212 in BRAF mutation-positive melanoma subjects previously treated with a BRAF inhibitor is under investigation (NCT01037127).[44]

AKT

Negative_regulation (inhibition) of MEK associated with skin cancer
9) Confidence 0.42 Published 2010 Journal Journal of Carcinogenesis Section Body Doc Link PMC2862505 Disease Relevance 0.52 Pain Relevance 0.05
However, we do show that the contribution of the spinal cord to the reduced behavioral effect is paramount since the activation of ERK1 and ERK2 is also decreased following formalin injection in the DN MEK mice relative to wild type littermates, and the behavioral and biochemical inhibition can be mimicked by intrathecal administration of MEK inhibitors.
Negative_regulation (inhibitors) of MEK in spinal cord associated with intrathecal and spinal cord
10) Confidence 0.42 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.33 Pain Relevance 0.29
Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner.
Negative_regulation (inhibitors) of MEK
11) Confidence 0.40 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20399747 Disease Relevance 0.29 Pain Relevance 0.22
However, there was a significant reduction of the ascending part of the second phase of the formalin test in both male and female DN MEK mice (Fig 1).
Negative_regulation (reduction) of DN MEK
12) Confidence 0.36 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.80 Pain Relevance 0.65
Therefore, the decreased levels of MDK mRNA in CRPC may suggest that the AR is reactivated in CRPC.


Negative_regulation (decreased) of MDK associated with reprotox - general 1
13) Confidence 0.35 Published 2010 Journal BMC Med Genomics Section Body Doc Link PMC2956710 Disease Relevance 0.82 Pain Relevance 0
In previous reports, not only L-LTP but also E-LTP were inhibited by the MEK inhibitor, PD98059 [16,38].
Negative_regulation (inhibitor) of MEK associated with long-term potentiation
14) Confidence 0.32 Published 2007 Journal Mol Pain Section Body Doc Link PMC2245920 Disease Relevance 0 Pain Relevance 0.91
It has been also demonstrated that the FERM (band 4.1, ezrin, radixin, moesin) domain of PTPH1 is necessary for the inhibition of Mek, Erk, Jnk and AP-1 and also for localization of the phosphatase on the plasma membrane of Jurkat T cells [14].
Negative_regulation (inhibition) of Mek in T cells
15) Confidence 0.30 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2873500 Disease Relevance 0.16 Pain Relevance 0.03
Pre-treatment of wild-type mice with SL327 (50 mg/kg i.p.), a specific inhibitor of mitogen-activated protein kinase kinase (MEK), the upstream kinase of ERK, fully prevented the development of tolerance to THC-induced hypolocomotion.
Negative_regulation (inhibitor) of MEK associated with tolerance
16) Confidence 0.29 Published 2005 Journal J. Neurochem. Section Abstract Doc Link 15857401 Disease Relevance 0.15 Pain Relevance 0.37
Effects of 48 h combined inhibition of MEK and mTOR on tumour proliferation
Negative_regulation (inhibition) of MEK associated with cancer
17) Confidence 0.28 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2955043 Disease Relevance 0.37 Pain Relevance 0
The SNC80-induced neural differentiation was also inhibited by treatment with the protein kinase C (PKC) inhibitor, phosphatidylinositol 3-kinase (PI3K) inhibitor, mitogen-activated protein kinase kinase (MEK) inhibitor or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor.
Negative_regulation (inhibitor) of MEK in neural associated with kinase c
18) Confidence 0.27 Published 2006 Journal J. Neurochem. Section Abstract Doc Link 16696856 Disease Relevance 0.21 Pain Relevance 0.51
In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test.
Negative_regulation (inhibitor) of MEK associated with cognitive disorder and orphanin
19) Confidence 0.25 Published 2010 Journal Neurobiol Learn Mem Section Abstract Doc Link 20026233 Disease Relevance 0.50 Pain Relevance 0.62
Similarly, COX-1, COX-2, MEK or p38 MAP kinase inhibitors reduced the nociceptive effect produced by PMA.
Negative_regulation (inhibitors) of MEK associated with nociception
20) Confidence 0.24 Published 2005 Journal Pain Section Abstract Doc Link 16099101 Disease Relevance 0.75 Pain Relevance 0.42

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