INT279383

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Context Info
Confidence 0.06
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 2
Total Number 19
Disease Relevance 16.02
Pain Relevance 3.37

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

cytosol (Ttpa) transport (Ttpa) intracellular (Ttpa)
cytoplasm (Ttpa)
Anatomy Link Frequency
macrophages 1
uterus 1
thyroid 1
finger 1
arm 1
Ttpa (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 2088 98.68 Very High Very High Very High
cytokine 594 97.96 Very High Very High Very High
Inflammatory response 72 78.60 Quite High
Kinase C 72 74.16 Quite High
Arthritis 90 73.56 Quite High
chemokine 180 73.28 Quite High
Inflammatory stimuli 54 69.36 Quite High
vincristine 3 58.40 Quite High
cINOD 90 29.52 Quite Low
Inflammatory mediators 18 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Cancer 2605 99.84 Very High Very High Very High
Hepatocellular Cancer 36 99.84 Very High Very High Very High
Metastasis 163 99.12 Very High Very High Very High
INFLAMMATION 2160 98.68 Very High Very High Very High
Breast Cancer 90 98.48 Very High Very High Very High
Inflammatory Bowel Disease 72 96.80 Very High Very High Very High
Glioma 36 96.44 Very High Very High Very High
Chronic Disease 18 95.40 Very High Very High Very High
Lymphatic System Cancer 100 94.48 High High
Congenital Anomalies 36 93.44 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
TTP mRNA and protein levels are significantly decreased in tumors of the thyroid, lung, ovary, uterus, and breast compared to non-transformed tissues [153].
Negative_regulation (decreased) of TTP mRNA in uterus associated with cancer
1) Confidence 0.06 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.79 Pain Relevance 0.18
Additionally, loss of TTP in cancer increases HIF1?
Negative_regulation (loss) of TTP associated with cancer
2) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 1.00 Pain Relevance 0.03
Here, loss of TTP can be linked to overexpression of TTP mRNA targets that are involved in inflammation and cancer such as VEGF [163].
Negative_regulation (loss) of TTP associated with inflammation and cancer
3) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.92 Pain Relevance 0.07
Loss of TTP in hepatocellular carcinoma is thought to lead to an increase in HIF1?
Negative_regulation (Loss) of TTP associated with hepatocellular cancer
4) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.90 Pain Relevance 0.05
These are modulated during cellular stimulation by inactivation of RNA decay-promoting proteins such as zinc-finger protein, tristetraprolin (TTP) [4], K-homology splicing-regulatory protein (KSRP) [5], butyrate response factor 1 and 2 [6], and certain gene products of the AU-rich element (ARE)/poly(U)-binding/degradation factor 1 (AUF1) [7].
Negative_regulation (inactivation) of TTP in finger
5) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.50 Pain Relevance 0.18
Continued secretion of cytokines and growth factors during chronic inflammation and cancer contribute to a prolonged state of activated pathways such as the MAPK pathway that maintains mRNA stabilization by inactivation of RNA-binding proteins that participate in mRNA decay such as TTP and KSRP (Fig. 2).
Negative_regulation (inactivation) of TTP associated with inflammation, cancer and cytokine
6) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.97 Pain Relevance 0.21
Thus, it is possible that dysfunction in IL-10 production would lead to reduced TTP levels and subsequently elevated pro-inflammatory cytokines.
Negative_regulation (reduced) of TTP associated with inflammation and cytokine
7) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 1.64 Pain Relevance 0.65
It is not necessarily that TTP levels are reduced in order to observe reduced TTP-induced mRNA decay, since phosphorylation of TTP due to aberration in signaling pathways, such as overactivated p38 MAPK, is a defect that is observed in several cancers.
Negative_regulation (reduced) of TTP associated with cancer
8) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.85 Pain Relevance 0.13
A possible mechanism of TTP deficiency in tumor cell lines and tumors is silencing of TTP promoter due to epigenetic alterations as a result of changes in DNA methylation or altered chromatin [71].
Negative_regulation (deficiency) of TTP associated with cancer
9) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 1.00 Pain Relevance 0.07
, IL-6, and IL-10 exclusively through TTP phosphorylation such as in murine bone marrow-derived macrophages [126].These above studies and others offer strong evidence for the p38 MAPK regulation of ARE-mRNA stability and the association with loss of TTP function.
Negative_regulation (loss) of TTP in macrophages
10) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.41 Pain Relevance 0.13
Overexpression and cytoplasmic localization of stabilizing ARE binding proteins, notably HuR, with commitment functional loss of RNA decay-promoting proteins such as TTP can be associated with chronic inflammation and cancer.
Negative_regulation (loss) of TTP associated with inflammation and cancer
11) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 1.29 Pain Relevance 0.20
Cooperative action of p38 MAPK and ERK pathways can be necessary for optimal ARE-mRNA stabilization, particularly in the case of inhibition of TTP [120].
Negative_regulation (inhibition) of TTP
12) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.33 Pain Relevance 0.28
Possible loss of TTP and probably other ARE-mRNA decay-promoting proteins is overexpression of miRNAs that target the mRNAs of these proteins; the miR-29a which may be overexpressed in breast cancer tissues can suppress TTP [165].
Negative_regulation (loss) of TTP associated with breast cancer
13) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 1.05 Pain Relevance 0.16
Loss of TTP is observed in the highly metastatic breast tumor line, MDA-MB-231, that is functionally associated with increased invasion and elevated expression of uPA and uPAR mRNAs due to their stabilization [162].
Negative_regulation (Loss) of TTP in MDA-MB-231 associated with breast cancer
14) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.73 Pain Relevance 0.14
One of those is the p38 MAPK pathway that leads to phosphorylation and inactivation of the activity of the RNA decay-promoting proteins such as TTP and KSRP.
Negative_regulation (inactivation) of TTP
15) Confidence 0.04 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.94 Pain Relevance 0.33
TTP mRNA and protein levels are significantly decreased in tumors of the thyroid, lung, ovary, uterus, and breast compared to non-transformed tissues [153].
Negative_regulation (decreased) of TTP mRNA in ovary associated with cancer
16) Confidence 0.02 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.79 Pain Relevance 0.18
TTP mRNA and protein levels are significantly decreased in tumors of the thyroid, lung, ovary, uterus, and breast compared to non-transformed tissues [153].
Negative_regulation (decreased) of TTP mRNA in thyroid associated with cancer
17) Confidence 0.02 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.79 Pain Relevance 0.18
TTP mRNA and protein levels are significantly decreased in tumors of the thyroid, lung, ovary, uterus, and breast compared to non-transformed tissues [153].
Negative_regulation (decreased) of TTP mRNA in lung associated with cancer
18) Confidence 0.02 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.79 Pain Relevance 0.18
ORRs were similar, but median TTP was significantly reduced in the CHOP arm (2.6 years).
Negative_regulation (reduced) of TTP in arm
19) Confidence 0.02 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727901 Disease Relevance 0.31 Pain Relevance 0.03

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