INT89395

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Context Info
Confidence 0.58
First Reported 2000
Last Reported 2011
Negated 0
Speculated 4
Reported most in Abstract
Documents 127
Total Number 131
Disease Relevance 70.27
Pain Relevance 12.54

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 (AKT1) nucleoplasm (AKT1) transport (AKT1)
small molecule metabolic process (AKT1) enzyme binding (AKT1) carbohydrate metabolic process (AKT1)
Anatomy Link Frequency
capsule 2
SW480 2
colon 2
MKN-45 2
HL-60 1
AKT1 (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 219 99.98 Very High Very High Very High
COX2 17 99.86 Very High Very High Very High
COX-2 inhibitor 269 99.76 Very High Very High Very High
diclofenac 48 99.22 Very High Very High Very High
agonist 93 99.00 Very High Very High Very High
Morphine 16 98.80 Very High Very High Very High
Inflammation 407 98.76 Very High Very High Very High
dexamethasone 443 98.32 Very High Very High Very High
Nicotine 81 98.24 Very High Very High Very High
aspirin 64 97.76 Very High Very High Very High
Disease Link Frequency Relevance Heat
Apoptosis 2716 99.96 Very High Very High Very High
Muscular Atrophy 50 99.96 Very High Very High Very High
Reprotox - General 1 137 99.84 Very High Very High Very High
Cancer 2717 99.80 Very High Very High Very High
Glioblastoma 53 99.78 Very High Very High Very High
Colon Cancer 527 99.48 Very High Very High Very High
Shock 13 99.42 Very High Very High Very High
Endometrial Cancer 112 99.32 Very High Very High Very High
Cholangiocarcinoma 2 99.24 Very High Very High Very High
Hyperplasia 46 99.12 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In conclusion, our results provide evidence that down-regulation of Akt pathway and MMP-2 may be one of the mechanisms by which sulindac and its metabolites inhibit glioblastoma cell invasion.
Negative_regulation (down-regulation) of Akt associated with glioblastoma
1) Confidence 0.58 Published 2005 Journal J. Cell. Biochem. Section Abstract Doc Link 15546138 Disease Relevance 0.65 Pain Relevance 0.15
In the present study, we demonstrate that down-regulation of Akt is a major effect of anti-invasiveness property of sulindac and its metabolites in glioblastoma cells.
Negative_regulation (down-regulation) of Akt associated with glioblastoma
2) Confidence 0.58 Published 2005 Journal J. Cell. Biochem. Section Abstract Doc Link 15546138 Disease Relevance 0.48 Pain Relevance 0.13
Sulindac and its metabolites inhibit invasion of glioblastoma cells via down-regulation of Akt/PKB and MMP-2.
Negative_regulation (down-regulation) of Akt associated with glioblastoma
3) Confidence 0.58 Published 2005 Journal J. Cell. Biochem. Section Title Doc Link 15546138 Disease Relevance 0.59 Pain Relevance 0.15
Together, these results show that naltrindole is a new inhibitor of the Akt/PKB signaling pathway, suggesting that naltrindole could be a potential lead for the development of a new type of inhibitors that target the constitutively active Akt/PKB signaling-dependent SCLC cells.
Negative_regulation (inhibitor) of Akt associated with small cell lung cancer
4) Confidence 0.57 Published 2004 Journal Cancer Res. Section Abstract Doc Link 15574783 Disease Relevance 0.70 Pain Relevance 0.08
The involvement of PI3K/Akt inhibition and p27 upregulation, as well as hypophosphorylation of Rac1 at ser71, were demonstrated.
Negative_regulation (inhibition) of Akt
5) Confidence 0.57 Published 2010 Journal Mol. Carcinog. Section Abstract Doc Link 19908241 Disease Relevance 0.96 Pain Relevance 0.45
As shown in Fig. 1B, following 16 hours of butyrate treatment, the levels of Akt1 and Akt2 mRNA were reduced by about 70% and 50% respectively as compared to untreated control cells.
Negative_regulation (reduced) of Akt1
6) Confidence 0.54 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.40 Pain Relevance 0
It appears that these inhibitors repress Akt1 and Akt2 transcription thereby depleting the cellular Akt protein.
Negative_regulation (depleting) of Akt
7) Confidence 0.54 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.57 Pain Relevance 0
Cyclic AMP, an inducer of Akt phosphorylation, suppresses Akt inactivation, Bid cleavage, and DNA fragmentation.
Negative_regulation (inactivation) of Akt in cleavage
8) Confidence 0.54 Published 2004 Journal Free Radic. Biol. Med. Section Abstract Doc Link 15451068 Disease Relevance 0.53 Pain Relevance 0.38
Here, we demonstrate for the first time that treatment with either sulindac or sulindac sulfide results in a decrease in PKB activity, and we provide compelling evidence that this occurs through two distinct mechanisms.
Negative_regulation (decrease) of PKB
9) Confidence 0.54 Published 2006 Journal Int. J. Oncol. Section Abstract Doc Link 16685448 Disease Relevance 0.30 Pain Relevance 0.08
We subsequently examined the effects of treating the human pancreatic cancer cell lines BxPC-3 and PaCa-2 with a specific inhibitor of the PI3K/Akt pathway, LY294002, in the presence or absence of the NSAID sulindac.
Negative_regulation (inhibitor) of Akt in BxPC-3 associated with pancreatic cancer and cinod
10) Confidence 0.51 Published 2003 Journal J. Gastrointest. Surg. Section Abstract Doc Link 12654560 Disease Relevance 0.56 Pain Relevance 0.42
Inhibition of Akt has been shown to induce apoptosis [33-35] and was shown to be a downstream target of NF-?
Negative_regulation (Inhibition) of Akt associated with apoptosis
11) Confidence 0.50 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 1.00 Pain Relevance 0.16
Insulin-stimulated phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively, after ECC (P < 0.05).
Negative_regulation (reduced) of Akt
12) Confidence 0.50 Published 2000 Journal Am. J. Physiol. Endocrinol. Metab. Section Abstract Doc Link 10893341 Disease Relevance 0.57 Pain Relevance 0.04
Taken together, these results suggest that inhibition of AKT1 extensively augments Par-4/p65 interactions in cytosol and consequently blocks nuclear translocation of p65.


Negative_regulation (inhibition) of AKT1
13) Confidence 0.47 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2883962 Disease Relevance 0.11 Pain Relevance 0
In this report, we showed a PI3K/AKT/glycogen synthase kinase-3beta (GSK-3beta) pathway regulates NAG-1 expression in human colorectal cancer cells as assessed by the inhibition of PI3K, AKT, and GSK-3beta.
Negative_regulation (inhibition) of AKT associated with colon cancer
14) Confidence 0.46 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15377673 Disease Relevance 0.59 Pain Relevance 0.24
Furthermore, only celecoxib showed Akt phosphorylation reduction and an anti-invasivness in glioblastoma cells, whereas aspirin, ketoprofen, ketorolac, and naproxen did not.
Negative_regulation (reduction) of Akt associated with aspirin, glioblastoma and acular
15) Confidence 0.43 Published 2005 Journal J. Cell. Biochem. Section Abstract Doc Link 15546138 Disease Relevance 0.65 Pain Relevance 0.23
These targets include the activation of apoptosis; suppression of growth factor expression or signalling; downregulation of antiapoptotic proteins; suppression of phosphatidylinositol-3'-kinase/Akt, NF-kappaB, Janus kinase-signal transducer and activator of transcription and activator protein-1 signalling pathways; and downregulation of angiogenesis through inhibition of vascular endothelial growth factor expression, cyclooxygenase-2, matrix metalloproteinase-9, urokinase-type plasminogen activator, adhesion molecules and cyclin D1.
Negative_regulation (suppression) of Akt associated with metalloproteinase, apoptosis and adhesions
16) Confidence 0.42 Published 2004 Journal Expert Opin Investig Drugs Section Abstract Doc Link 15461561 Disease Relevance 0.77 Pain Relevance 0.10
Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer cells.
Negative_regulation (Inhibition) of PKB associated with cox-2 inhibitor, apoptosis and stomach cancer
17) Confidence 0.42 Published 2006 Journal Digestion Section Title Doc Link 16641552 Disease Relevance 0.38 Pain Relevance 0.14
CE has been shown to induce apoptosis in various cancer cells lines through a COX2-independent mechanism that seems to involve inactivation of protein kinase Akt and inhibition of endoplasmic reticulum (ER) Ca2+ ATPase.
Negative_regulation (inactivation) of Akt in reticulum associated with cancer, cox2 and apoptosis
18) Confidence 0.42 Published 2006 Journal Mol. Pharmacol. Section Abstract Doc Link 16467190 Disease Relevance 0.54 Pain Relevance 0.51
Sulindac and its metabolites inhibit invasion of glioblastoma cells via down-regulation of Akt/PKB and MMP-2.
Negative_regulation (down-regulation) of PKB associated with glioblastoma
19) Confidence 0.42 Published 2005 Journal J. Cell. Biochem. Section Title Doc Link 15546138 Disease Relevance 0.60 Pain Relevance 0.15
Recently, Hideshima et al. showed that perifosine, an alkylphospholipid, is active in-vitro against myelomatous cells by inhibiting the phosphatidilinositol 3-kinase/Akt, a mitogen-activated protein kinase which mediates MM cell resistance to conventional therapies [29].
Negative_regulation (inhibiting) of Akt associated with multiple myeloma
20) Confidence 0.42 Published 2007 Journal World J Surg Oncol Section Body Doc Link PMC1913918 Disease Relevance 0.30 Pain Relevance 0.03

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