INT41721

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Context Info
Confidence 0.58
First Reported 1982
Last Reported 2010
Negated 2
Speculated 1
Reported most in Body
Documents 40
Total Number 48
Disease Relevance 32.49
Pain Relevance 2.83

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
circulating cells 1
blood 1
endothelial cells 1
spinal cord 1
neurons 1
MTOR (Homo sapiens)
Pain Link Frequency Relevance Heat
spinal dorsal horn 2 99.44 Very High Very High Very High
Nerve growth factor 7 96.96 Very High Very High Very High
Pain 33 96.84 Very High Very High Very High
Neuropeptide 2 96.32 Very High Very High Very High
substance P 2 95.80 Very High Very High Very High
withdrawal 10 95.68 Very High Very High Very High
cytokine 82 93.16 High High
Spinal cord 2 91.56 High High
Calcitonin gene-related peptide 1 91.04 High High
opioid receptor 10 90.80 High High
Disease Link Frequency Relevance Heat
Breast Cancer 311 99.96 Very High Very High Very High
Apoptosis 381 99.92 Very High Very High Very High
Thrombosis 61 99.88 Very High Very High Very High
Metabolic Syndrome 416 99.74 Very High Very High Very High
Obstructive Sleep Apnea 219 99.52 Very High Very High Very High
Cancer 796 99.32 Very High Very High Very High
Focal Segmental Glomerulosclerosis 1 99.30 Very High Very High Very High
Cyst 42 99.04 Very High Very High Very High
Renal Cell Carcinoma 232 98.84 Very High Very High Very High
Immunotherapy Of Cancer 23 98.76 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Interestingly, podocyte damage and focal segmental glomerulosclerosis can occur after treatment with an mTOR inhibitor in some transplant patients.
Negative_regulation (inhibitor) of mTOR in podocyte associated with focal segmental glomerulosclerosis
1) Confidence 0.58 Published 2009 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 19019920 Disease Relevance 0.38 Pain Relevance 0.05
Phosphorylation of p70 S6 kinase and 4E-BP1 is also repressed by PI3K inhibitors as well as by rapamycin, the selective inhibitor of FRAP/mTOR.
Negative_regulation (inhibitor) of mTOR
2) Confidence 0.57 Published 1998 Journal J. Biol. Chem. Section Abstract Doc Link 9722592 Disease Relevance 0.07 Pain Relevance 0.43
Phosphorylation of p70 S6 kinase and 4E-BP1 is also repressed by PI3K inhibitors as well as by rapamycin, the selective inhibitor of FRAP/mTOR.
Negative_regulation (inhibitor) of FRAP
3) Confidence 0.57 Published 1998 Journal J. Biol. Chem. Section Abstract Doc Link 9722592 Disease Relevance 0.07 Pain Relevance 0.43
TDA induced by vinpocetine has been demonstrated to be followed by depletion of the marker enzyme fluoride-resistant acid phosphatase (FRAP) and its isoenzyme thiamine monophosphatase (TMP), and by the decrease in the pain-related neuropeptide substance P from laminae I-II-(III) from the segmentally related, ipsilateral substance of Rolando of the spinal cord.
Negative_regulation (depletion) of FRAP in spinal cord associated with pain, frailty, neuropeptide, spinal cord and substance p
4) Confidence 0.57 Published 2008 Journal Ann. Anat. Section Abstract Doc Link 18413267 Disease Relevance 0.69 Pain Relevance 0.41
Everolimus (Afinitor®; RAD001; Novartis, USA) is an orally bioavailable mTOR inhibitor that binds with high affinity to its intracellular receptor FKBP12, at the same point in the mTOR pathway as temosirolimus.
Negative_regulation (inhibitor) of mTOR
5) Confidence 0.55 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.50 Pain Relevance 0
Another mechanism of resistance involves increased insulin growth factor-1 receptor (IGF-1R)/PI3K/AKT signaling as a result of loss of mTOR/S6K inhibition whilst on therapy which limits the antitumor effect of mTOR inhibitors.
Negative_regulation (inhibition) of mTOR associated with hyperinsulinism
6) Confidence 0.55 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.30 Pain Relevance 0
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]
Negative_regulation (inhibitors) of mTOR associated with vascular disease and thrombosis
7) Confidence 0.52 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.88 Pain Relevance 0.08
Reduced mTOR has many important consequences for cell metabolism and life span.
Negative_regulation (Reduced) of mTOR
8) Confidence 0.52 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.41 Pain Relevance 0.04
Consequently, the significant reduction of mTOR found in MetS patients suggests that mTOR might be, in part, responsible for increased cardiovascular thrombotic diseases seen in MetS.
Negative_regulation (reduction) of mTOR associated with metabolic syndrome and disease
9) Confidence 0.52 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.77 Pain Relevance 0.14
Inhibition of mTOR reduces translocation of a subset of mRNAs and dramatically represses ribosomal mRNA and tRNA transcription.
Negative_regulation (Inhibition) of mTOR
10) Confidence 0.52 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.46 Pain Relevance 0.05
This would indicate that mTOR inhibition is crucial to decrease thrombotic events.
Negative_regulation (inhibition) of mTOR
11) Confidence 0.52 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2940873 Disease Relevance 0.74 Pain Relevance 0.14
In the setting of hormone receptor positive breast cancer, mTOR inhibition and the resulting increase in Akt signaling could result in ER phosphorylation on Ser167 and negate the effects of aromatase inhibition, thus limiting the therapeutic benefit of this combination.


Negative_regulation (inhibition) of mTOR associated with breast cancer
12) Confidence 0.44 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2242654 Disease Relevance 0.65 Pain Relevance 0
This subset of cancers may be resistant to strategies targeting upstream growth factor receptors, but particularly sensitive to PI3K or mTOR inhibition.
Negative_regulation (inhibition) of mTOR associated with cancer
13) Confidence 0.44 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2242654 Disease Relevance 0.59 Pain Relevance 0
PI3K, AKT, and mTOR have been targeted individually by various drugs, but XL765 is the first oral dual PI3K and mTOR inhibitor with Phase I trial results, reported by Papadopoulos et al [25].
Negative_regulation (inhibitor) of mTOR
14) Confidence 0.43 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2647552 Disease Relevance 0.77 Pain Relevance 0
Transcutaneous iontophoresis of microtubule inhibitors (Vinblastin, Vincristin, Formyl-Leurosin) in rats induces depletion of fluoride-resistant acid phosphatase (FRAP) and transganglionic degenerative atrophy (trggl. deg. atr.) of the central terminals of primary nociceptive neurons, probably via blockade of axoplasmic transport in the peripheral sensory nerves.
Spec (probably) Negative_regulation (depletion) of FRAP in neurons associated with nociception and frailty
15) Confidence 0.42 Published 1982 Journal Acta Neurol. Scand. Section Abstract Doc Link 6183918 Disease Relevance 0.73 Pain Relevance 0.28
Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP).
Negative_regulation (depletion) of FRAP in dorsal horn associated with nerve growth factor, spinal dorsal horn and frailty
16) Confidence 0.42 Published 2007 Journal Ann. Anat. Section Abstract Doc Link 17319607 Disease Relevance 0.35 Pain Relevance 0.53
The study also revealed that the benefit of mTOR inhibition might be greater in papillary renal carcinoma than in clear cell carcinoma.17
Negative_regulation (inhibition) of mTOR associated with carcinoma and renal cell carcinoma
17) Confidence 0.40 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.53 Pain Relevance 0
Their unique action is attributed to their effect directly on the tumor cells themselves, in part due to HIF downregulation, and on tumor endothelial cells by blocking proliferation and survival signals downstream of the VEGF receptor.23–25 One study has also shown that the benefits of mTOR inhibition may be greater in papillary renal carcinoma than in clear cell carcinoma; papillary subtype accounting for 10% to 15% of renal cell cancers.26 This is postulated to be due to HIF upregulation which is noted in patients with papillary renal cell carcinoma associated with fumarate–hydratase mutations.27
Negative_regulation (inhibition) of mTOR in endothelial cells associated with cancer, carcinoma and renal cell carcinoma
18) Confidence 0.40 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.90 Pain Relevance 0
Here we review another mTOR inhibitor, everolimus (Afinitor®; Novartis, USA) which was approved in March 2009 by the US FDA for treatment of targeted-therapy refractory metastatic renal cell cancer.
Negative_regulation (inhibitor) of mTOR associated with renal cell carcinoma
19) Confidence 0.40 Published 2010 Journal Cancer management and research Section Abstract Doc Link PMC3004583 Disease Relevance 0.58 Pain Relevance 0
Temsirolimus (Torisel®; Wyeth, USA), was the first mTOR inhibitor to be approved for treatment of RCC.
Negative_regulation (inhibitor) of mTOR associated with renal cell carcinoma
20) Confidence 0.40 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.92 Pain Relevance 0

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