INT213923

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Context Info
Confidence 0.65
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 16
Total Number 16
Disease Relevance 9.28
Pain Relevance 0.70

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

mitochondrion (MTOR) Golgi apparatus (MTOR) endoplasmic reticulum (MTOR)
cytoplasm (MTOR) cytosol (MTOR) signal transduction (MTOR)
Anatomy Link Frequency
lymphocyte 2
skeletal muscle 1
MTOR (Homo sapiens)
Pain Link Frequency Relevance Heat
cytokine 74 99.98 Very High Very High Very High
Inflammation 51 99.76 Very High Very High Very High
withdrawal 12 90.96 High High
abatacept 5 75.28 Quite High
agonist 4 44.32 Quite Low
rheumatoid arthritis 1 8.32 Low Low
psoriasis 1 6.32 Low Low
tolerance 17 5.00 Very Low Very Low Very Low
Pain 12 5.00 Very Low Very Low Very Low
imagery 5 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
INFLAMMATION 43 99.76 Very High Very High Very High
Vascular Disease 32 98.92 Very High Very High Very High
Cancer 85 98.26 Very High Very High Very High
Thrombosis 56 97.52 Very High Very High Very High
Metastasis 26 96.60 Very High Very High Very High
Metabolic Syndrome 416 95.88 Very High Very High Very High
Apoptosis 37 94.28 High High
Diabetes Mellitus 100 94.12 High High
Renal Cell Carcinoma 29 93.84 High High
Obesity 23 93.60 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Activation of mTOR promotes the proliferation and survival of tumor cells.
Positive_regulation (Activation) of mTOR associated with cancer
1) Confidence 0.65 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.90 Pain Relevance 0
This would suggest: 1) that cytokines impair IRS-1 activity, blocking anabolic insulin signaling cascade with less activated mTOR and 2) that the molecular mechanism of leptin-mediated impairment of insulin signaling is similar in both skeletal muscle and lymphocytes.
Positive_regulation (activated) of mTOR in lymphocytes associated with cytokine
2) Confidence 0.54 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.84 Pain Relevance 0.14
The increased incidence of vascular thrombosis when mTOR inhibitors are used and the improvement of micro-angiopathy when these drugs are withdrawn suggest the important role of mTOR in regulating vascular functions [8,9]
Positive_regulation (role) of mTOR associated with vascular disease and thrombosis
3) Confidence 0.44 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.86 Pain Relevance 0.07
However, the authors did not evaluate the downstream molecules involved in the intracellular insulin-mediated signaling including a fundamental molecule such as mTOR.
Positive_regulation (mediated) of mTOR
4) Confidence 0.44 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.68 Pain Relevance 0.03
Indeed, IS is a very complex phenomenon which is influenced not only by the cellular metabolic status but also interacts with circulating molecules such as hormones (including insulin), nutrients and inflammatory molecules. mTOR and mTOR homologues are activated by both specific cytosolic signals which monitor cellular metabolic status and by extracellular circulating molecules.
Positive_regulation (activated) of mTOR associated with inflammation
5) Confidence 0.44 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.95 Pain Relevance 0.05
Indeed, IS is a very complex phenomenon which is influenced not only by the cellular metabolic status but also interacts with circulating molecules such as hormones (including insulin), nutrients and inflammatory molecules. mTOR and mTOR homologues are activated by both specific cytosolic signals which monitor cellular metabolic status and by extracellular circulating molecules.
Positive_regulation (activated) of mTOR associated with inflammation
6) Confidence 0.44 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.95 Pain Relevance 0.05
Indeed, mTOR is stimulated by insulin signaling, nutrients, catabolic hormones, cytokines and growth factors [7].
Positive_regulation (stimulated) of mTOR associated with cytokine
7) Confidence 0.41 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.46 Pain Relevance 0.05
Current understanding of insulin signaling regulation considers IRS-1 to be a key protein in this cascade and mTOR activation.
Positive_regulation (activation) of mTOR
8) Confidence 0.41 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.64 Pain Relevance 0
Drugs may also act indirectly by antibody binding of elevated levels of extracellular angiogenic growth factors eg, bevacizumab (Avastin®, Genentech), acting on overexpressed receptors on tumor cells themselves eg, sunitinib, sorafenib (Nexavar®, Bayer) or by inhibiting related pathways such as mTOR upregulation of VEGF and HIF1?
Positive_regulation (upregulation) of mTOR associated with cancer
9) Confidence 0.39 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727778 Disease Relevance 0.69 Pain Relevance 0
In a model system of acquired resistance to letrozole, AEE788 partially restored sensitivity to letrozole, whereas rapamycin was not effective, suggesting that letrozole resistance and mTOR activation may not be connected in this model [43].
Positive_regulation (activation) of mTOR
10) Confidence 0.33 Published 2007 Journal Breast Cancer Res Treat Section Body Doc Link PMC2001220 Disease Relevance 0.28 Pain Relevance 0
The insulin activation of mTOR and S6K1 kinase works through the IRS-1/PI 3-kinase/Akt pathway, while amino acids seem to exert a direct effect on mTOR [41,42].
Positive_regulation (activation) of mTOR
11) Confidence 0.27 Published 2009 Journal Nutr Metab (Lond) Section Body Doc Link PMC2761378 Disease Relevance 0.25 Pain Relevance 0
Activation of mTOR and S6K1 kinase leads to serine phosphorylation of IRS-1, with a subsequent decline in tyrosine phosphorylation of IRS-1 and IRS-1-associated PI 3-kinase activity, as discussed above.
Positive_regulation (Activation) of mTOR
12) Confidence 0.27 Published 2009 Journal Nutr Metab (Lond) Section Body Doc Link PMC2761378 Disease Relevance 0.24 Pain Relevance 0
However, there was a significant increase in phosphorylated mTOR resulting in increased phosphorylation of S6K1 following both overfeeding diets (Figure 4).


Positive_regulation (increase) of mTOR
13) Confidence 0.27 Published 2009 Journal Nutr Metab (Lond) Section Body Doc Link PMC2761378 Disease Relevance 0 Pain Relevance 0
These cytokines activate the mTOR via the janus kinase 3 and phosphoinositide-3 kinase signal transduction pathways, leading to further propagation of the lymphocyte cell cycle.
Positive_regulation (activate) of mTOR in lymphocyte associated with cytokine
14) Confidence 0.26 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.09 Pain Relevance 0.17
Activated Akt has been shown to be associated with a worse prognosis in HNSCC as well, and trials are underway to study the safety and effectiveness of combining cetuximab and drugs inhibiting mTOR, a target downstream from Akt.93 Preclinical data have shown that the mTOR inhibitor rapamycin has anti-tumor activity in HNSCC in vivo.94 Thus, trials are ongoing to assess the activity of newer generation of mTOR inhibitors (temsirolimus, everolimus) with cisplatin and cetuximab in patients with metastatic disease.
Positive_regulation (generation) of mTOR associated with cancer and metastasis
15) Confidence 0.19 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2921255 Disease Relevance 0.51 Pain Relevance 0
This would suggest: 1) that cytokines impair IRS-1 activity, blocking anabolic insulin signaling cascade with less activated mTOR and 2) that the molecular mechanism of leptin-mediated impairment of insulin signaling is similar in both skeletal muscle and lymphocytes.
Positive_regulation (activated) of mTOR in skeletal muscle associated with cytokine
16) Confidence 0.18 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.84 Pain Relevance 0.14

General Comments

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