INT206136

Context Info Confidence 0.46 First Reported 2007 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 14 Total Number 15 Disease Relevance 4.30 Pain Relevance 1.10

nucleoplasm (STAT3) DNA binding (STAT3) cytoplasm (STAT3) signal transducer activity (STAT3) cell proliferation (STAT3) cytosol (STAT3)

Anatomy Link Frequency nucleus 8 myocardium 2 Th17 cell 2 astrocytes 2 STAT3 (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 156 98.76 Inflammation 178 95.88 Inflammatory response 21 91.28 dexamethasone 14 83.52 Inflammatory mediators 8 78.24 Crohn's disease 96 73.08 Acupuncture 6 56.32 agonist 45 50.00 anesthesia 18 45.44 fibrosis 7 32.80

Disease Link Frequency Relevance Heat Cancer 329 99.84 Glioma 102 96.66 INFLAMMATION 210 95.88 Inflammatory Bowel Disease 108 93.52 Hypoxia 5 93.40 Thrombosis 3 90.76 Coagulation Disorder 4 88.92 Acute-phase Reaction 7 88.40 Disease 165 73.08 Squamous Cell Neoplasms 6 64.56

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Event

Anatomy

Negation

Speculation

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However, our studies indicate that the tyrosine phosphorylation of STAT3 in 48 h PO myocardium does not appear to be required for the increased level of STAT3 in the nucleus, since the distribution of STAT3 or P-STAT3 between cytoplasm and nucleus was not significantly altered in 48 h PO myocardium.

Positive_regulation (increased) of Gene_expression (level) of STAT3 in nucleus

1) Confidence 0.46 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0.18 Pain Relevance 0.08

Our present studies indicate a novel mechanism of activation and redistribution of STAT3 in PO myocardium with the involvement of integrin-mediated BMX activation.

Positive_regulation (mediated) of Gene_expression (activation) of STAT3 in myocardium

2) Confidence 0.46 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0 Pain Relevance 0.06

In 48 RVPO cats, the levels of STAT3 and P-STAT3 in normally loaded LV control were similar to sham control cats, but the RV exhibited a substantial increase in STAT3 levels in both cytoplasmic and nuclear fractions.

Positive_regulation (increase) of Gene_expression (levels) of STAT3

3) Confidence 0.46 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0 Pain Relevance 0

However, our studies indicate that the tyrosine phosphorylation of STAT3 in 48 h PO myocardium does not appear to be required for the increased level of STAT3 in the nucleus, since the distribution of STAT3 or P-STAT3 between cytoplasm and nucleus was not significantly altered in 48 h PO myocardium.

Positive_regulation (required) of Gene_expression (distribution) of STAT3 in nucleus

4) Confidence 0.46 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0.18 Pain Relevance 0.08

However, our studies indicate that the tyrosine phosphorylation of STAT3 in 48 h PO myocardium does not appear to be required for the increased level of STAT3 in the nucleus, since the distribution of STAT3 or P-STAT3 between cytoplasm and nucleus was not significantly altered in 48 h PO myocardium.

Positive_regulation (required) of Gene_expression (level) of STAT3 in nucleus

5) Confidence 0.46 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0.18 Pain Relevance 0.08

The overall trend is supportive of a malignant glioma diagnosis playing a more meaningful role compared to steroids in elevated p-STAT-3 levels in this study; however, patients with other types of malignancies also have elevated PBMC p-STAT-3 expression [26] and the PBMC p-STAT-3 levels may be elevated in other medical conditions.

Positive_regulation (elevated) of Gene_expression (expression) of PBMC p-STAT-3 associated with glioma

6) Confidence 0.46 Published 2009 Journal J Transl Med Section Body Doc Link PMC2777138 Disease Relevance 0.39 Pain Relevance 0.08

The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients.

Positive_regulation (overexpressed) of Gene_expression (overexpressed) of STAT-3 associated with cancer

7) Confidence 0.46 Published 2009 Journal J Transl Med Section Abstract Doc Link PMC2777138 Disease Relevance 0.58 Pain Relevance 0

The increased expression of STAT3 responsive genes and expression of IL-6 within SCs demonstrate that IL-6/STAT3 signaling occurred in SCs, correlating with an increase in SC proliferation, evidenced by increased Pax7+/PCNA+ cell number in the early stages of the time-course.

Positive_regulation (increased) of Gene_expression (expression) of STAT3

8) Confidence 0.44 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2696599 Disease Relevance 0 Pain Relevance 0.03

However, upon RGD stimulation in this 3D model, STAT3 was recruited to the insoluble pellet fraction and P-STAT3 levels were increased both in the insoluble and soluble fractions (p<0.05).

Positive_regulation (increased) of Gene_expression (levels) of STAT3

9) Confidence 0.40 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2443357 Disease Relevance 0 Pain Relevance 0

However, many factors have been identified that induce p-STAT-3 expression, including growth factors and cytokines, such as IL-6 [44], elaborated by reactive astrocytes [45], epidermal growth factor [43], and Janus kinase 2 [46], and it is uncertain which of these, either individually or in combination, is the etiological agent for inducing p-STAT-3 in PBMC.

Positive_regulation (induce) of Gene_expression (expression) of STAT-3 in astrocytes associated with cytokine

10) Confidence 0.40 Published 2009 Journal J Transl Med Section Body Doc Link PMC2777138 Disease Relevance 0.54 Pain Relevance 0.08

The expression of constitutively active RhoG, Cdc42, and RhoA caused the translocation from the cytoplasm to the nucleus of cotransfected STAT3-GFP.

Positive_regulation (cotransfected) of Gene_expression (cotransfected) of STAT3-GFP in nucleus

11) Confidence 0.29 Published 2007 Journal Immun Ageing Section Body Doc Link PMC1845171 Disease Relevance 0.06 Pain Relevance 0.04

Activation of the Jak/Stat3 pathway by IL-6 through its high affinity receptor, IL-6R?

Positive_regulation (Activation) of Gene_expression (/) of Stat3

12) Confidence 0.29 Published 2010 Journal PPAR Research Section Body Doc Link PMC2829627 Disease Relevance 0.88 Pain Relevance 0.05

The associated increased ileal expression of the downstream signaling molecule STAT3 supports this assumption.

Positive_regulation (increased) of Gene_expression (expression) of STAT3

13) Confidence 0.27 Published 2010 Journal BMC Immunol Section Body Doc Link PMC3016394 Disease Relevance 0.08 Pain Relevance 0.21

Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged.

Neg (unchanged) Positive_regulation (unchanged) of Gene_expression (expression) of STAT3 in Th17 cell

14) Confidence 0.27 Published 2010 Journal BMC Immunol Section Abstract Doc Link PMC3016394 Disease Relevance 0.81 Pain Relevance 0.32

In one study, Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) was determined.

Positive_regulation (activation) of Gene_expression (synthesis) of STAT 3

15) Confidence 0.19 Published 2007 Journal Immun Ageing Section Body Doc Link PMC1845171 Disease Relevance 0.36 Pain Relevance 0

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