INT129584

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Context Info
Confidence 0.68
First Reported 2004
Last Reported 2010
Negated 2
Speculated 2
Reported most in Body
Documents 97
Total Number 100
Disease Relevance 87.07
Pain Relevance 14.86

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

cell proliferation (Stat3) signal transduction (Stat3) plasma membrane (Stat3)
nucleus (Stat3) DNA binding (Stat3) transcription factor binding (Stat3)
Anatomy Link Frequency
liver 4
brain 2
nucleus 2
fibroblasts 2
NK cells 2
Stat3 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammatory response 330 99.92 Very High Very High Very High
cytokine 1563 99.88 Very High Very High Very High
addiction 36 99.70 Very High Very High Very High
Inflammation 2371 99.48 Very High Very High Very High
tolerance 100 99.30 Very High Very High Very High
Inflammatory mediators 109 99.20 Very High Very High Very High
qutenza 7 99.20 Very High Very High Very High
Paracetamol 26 98.72 Very High Very High Very High
chemokine 204 98.18 Very High Very High Very High
fibrosis 340 97.54 Very High Very High Very High
Disease Link Frequency Relevance Heat
Cancer 7513 100.00 Very High Very High Very High
Metastasis 559 99.60 Very High Very High Very High
Injury 306 99.58 Very High Very High Very High
Reprotox - General 1 126 99.58 Very High Very High Very High
Obesity 1115 99.56 Very High Very High Very High
Necrosis 42 99.56 Very High Very High Very High
INFLAMMATION 2704 99.52 Very High Very High Very High
Hepatocellular Cancer 284 99.40 Very High Very High Very High
Lymphatic System Cancer 80 99.40 Very High Very High Very High
Skin Cancer 383 99.38 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
These cytoplasmic tyrosine kinases, often in conjunction with Jaks, are likely to mediate Stat3 activation subsequent to many other cancer-initiating, toxic insults, including UV-radiation, stress, and smoke [26,27].
Positive_regulation (activation) of Stat3 associated with stress and cancer
1) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.85 Pain Relevance 0.16
The abundance of cytokines that activate Stat3 within the tumour microenvironment, which comprises of members of the interleukin (IL) IL6, IL10 and IL17/23 families, underpins a signaling network that simultaneously promotes the growth of neoplastic epithelium, fuels inflammation and suppresses the host's anti-tumour immune response.
Positive_regulation (activate) of Stat3 in epithelium associated with inflammation, cancer and cytokine
2) Confidence 0.68 Published 2010 Journal Cell Div Section Abstract Doc Link PMC2887830 Disease Relevance 1.14 Pain Relevance 0.24
The preclinical observations cited above suggest that the growth and maintenance of many tumours, including some that are not caused by aberrant activation of Stat3, have become addicted to its continuous activation.
Positive_regulation (activation) of Stat3 associated with cancer
3) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.69 Pain Relevance 0
These two pathways converge in tumour cells and result in activation of the latent signal transducer and activator of transcription 3 (Stat3) which mediates a transcriptional response favouring survival, proliferation and angiogenesis.
Positive_regulation (activation) of Stat3 associated with cancer
4) Confidence 0.68 Published 2010 Journal Cell Div Section Abstract Doc Link PMC2887830 Disease Relevance 1.15 Pain Relevance 0.24
Excessive activation of Stat3 correlates with tumour invasion and metastasis in a variety of cancers [17,18] and high level of tyrosine-phosphorylated STAT3 is a pertinent feature in colon and gastric cancers associated with adverse outcomes [79] (Figure 1).
Positive_regulation (activation) of Stat3 in colon associated with cancer, stomach cancer and metastasis
5) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.96 Pain Relevance 0.03
The physical contact between tumour and antigen presenting cells also directly activates Stat3 and triggers a tolerogenic DC phenotype [128].
Positive_regulation (activates) of Stat3 associated with cancer
6) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 1.05 Pain Relevance 0.08
However, a variety of cancers harbour activating point mutations in Jak2 [44] and gp130 in-frame deletion mutations, which mediate ligand-independent activation of Stat3, are found in hepatocellular carcinomas [45].
Neg (independent) Positive_regulation (activation) of Stat3 associated with cancer and hepatocellular cancer
7) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.82 Pain Relevance 0.17
However, due to extensive redundancy among cytokines that activate Stat3, direct inhibition of Stat3 (activity) may show additional therapeutic benefits.
Positive_regulation (activate) of Stat3 associated with cytokine
8) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.80 Pain Relevance 0.15
Stat3 is aberrantly activated in a majority of cancers of epithelial origin [17,18].
Positive_regulation (activated) of Stat3 associated with cancer
9) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 1.55 Pain Relevance 0.36
Even though there is no evidence for tumour-specific amplification of the STAT3 locus in humans, excessive activation of endogenous Stat3 reproducibly promotes gastric adenoma formation in gp130Y757F mice at a very young age.
Positive_regulation (activation) of Stat3 associated with adenoma and cancer
10) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 1.44 Pain Relevance 0.17
Owing to their capacity to inactivate upstream tyrosine kinases or to sequester phosphorylated Stat3 from de novo Stat-dimers, mutagenic alterations in the cytosolic tyrosine phosphatases CD45 [50,51], SHP1 and SHP2 [50,51], or the SUMO E3 ligase Pias3 [52] and Grim19 [53] are also expected to result in excessive activation of Stat3-dependent target genes.


Positive_regulation (activation) of Stat3
11) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.79 Pain Relevance 0.03
Excessive activation of Stat3 can also result from impairment mutations affecting any of the negative regulatory proteins which limit the extent of Stat3 activation under physiological conditions [46].
Positive_regulation (activation) of Stat3
12) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.76 Pain Relevance 0.13
Similarly, sustained gp130 and Stat3 activation in Socs3-deficient macrophages triggers a strong anti-inflammatory response [41-43] and expression of the canonical TGF?
Positive_regulation (activation) of Stat3 in macrophages associated with inflammatory response
13) Confidence 0.68 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 0.85 Pain Relevance 0.36
This indomethacin-induced injury was associated with activation of IL-6-STAT3 signaling, increased expression of alpha(1)-AT mRNA, and greater accumulation of mutant polymerized alpha(1)-ATZ protein in livers of indomethacin-treated PiZ mice compared to vehicle-treated PiZ animals.
Positive_regulation (activation) of STAT3 in livers associated with injury
14) Confidence 0.67 Published 2006 Journal Hepatology Section Abstract Doc Link 17006946 Disease Relevance 1.10 Pain Relevance 0.23
Stat3 activity in tumor cells inhibits the production of pro-inflammatory cytokines and chemokines while inducing the release of factors that inhibit dendritic cell (DC) maturation through activation of Stat3 in DCs.
Positive_regulation (activation) of Stat3 in dendritic cell associated with chemokine, inflammation, cancer and cytokine
15) Confidence 0.58 Published 2004 Journal J Transl Med Section Body Doc Link PMC441417 Disease Relevance 1.60 Pain Relevance 0.19
Activation of STAT3 began on time at 3 hours but persisted strongly up to 72 hours despite significant accumulation of SOCS3.
Positive_regulation (Activation) of STAT3
16) Confidence 0.56 Published 2006 Journal Hepatology Section Abstract Doc Link 17133485 Disease Relevance 0.53 Pain Relevance 0.07
Alternatively, hepatoprotective STAT3 activation was decreased in SOCS3Tg hepatocytes, an event that was associated with augmented SOCS3 expression in the hepatocytes.
Positive_regulation (activation) of STAT3 in hepatocytes
17) Confidence 0.55 Published 2007 Journal J. Immunol. Section Abstract Doc Link 17339476 Disease Relevance 0.81 Pain Relevance 0.40
Importantly, heat shock protein 60 released by tumor cells caused a persistent activation of TLR2 and was critical in the constitutive activation of transcription factor Stat3, leading to the release of immunosuppressive cytokines and chemokines.
Positive_regulation (activation) of Stat3 associated with chemokine, cancer, shock and cytokine
18) Confidence 0.54 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2716531 Disease Relevance 1.28 Pain Relevance 0.14
Fourthly, the TLR2 activation of Stat3 is partially dependent of IL-6 and IL-10.
Positive_regulation (activation) of Stat3
19) Confidence 0.54 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2716531 Disease Relevance 0.60 Pain Relevance 0.03
These results are consensually supported by the studies in which TLR4 activation inhibits phosphorylation and nucleus translocation of Stat3 [21] and activated Stat3 inhibits TLR4 signaling in return via inhibiting transcriptional or translational activity of NF-?
Positive_regulation (activated) of Stat3 in nucleus
20) Confidence 0.54 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2716531 Disease Relevance 1.36 Pain Relevance 0.06

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