INT64170

Context Info Confidence 0.46 First Reported 1996 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 31 Total Number 41 Disease Relevance 14.96 Pain Relevance 3.99

cell differentiation (GLI2) cell proliferation (GLI2) nucleus (GLI2) intracellular (GLI2) cilium (GLI2) cytoplasm (GLI2)

Anatomy Link Frequency THP-1 10 macrophages 9 monocytes 6 MDA-MB-231 2 hair follicle 1 GLI2 (Homo sapiens)

Pain Link Frequency Relevance Heat COX-2 inhibitor 130 100.00 cytokine 107 99.84 cINOD 114 99.32 Inflammation 158 99.16 Mechanotransduction 88 98.20 agonist 76 97.80 chemokine 86 95.00 aspirin 6 93.76 rheumatoid arthritis 201 90.20 analgesia 5 82.96

Disease Link Frequency Relevance Heat Cancer 943 99.84 Apoptosis 310 99.32 INFLAMMATION 207 99.16 Atherosclerotic Plaque 35 98.84 Medulloblastoma 10 98.80 Colon Cancer 134 97.72 Hypertension 11 97.24 Death 77 95.16 Breast Cancer 74 93.92 Renal Disease 6 93.76

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Event

Anatomy

Negation

Speculation

Pain term

Disease term

When MDA-MB-231 or RWGT2 tumor cells were grown on rigid substrates (1.7 and 67 GPa) with moduli bracketing that of mineralized bone matrix (18.4 GPa) [35], both Gli2 and PTHrP expression were 2–4 times higher compared to soft PAA gels (0.45 kPa).

Gene_expression (expression) of Gli2 in MDA-MB-231 associated with cancer

1) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.86 Pain Relevance 0

While ROCK is ubiquitously expressed in many tissues and cells in the body, the postnatal expression of Gli2 is primarily restricted to the growth plate [45] and hair follicle [46], [47].

Gene_expression (expression) of Gli2 in hair follicle

2) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.81 Pain Relevance 0.03

The expression of PTHrP, Gli2, and TGF-ß was measured by quantitative RT-PCR using validated TaqMan primers with the 7300 Real-Time PCR System (Applied Biosciences).

Gene_expression (expression) of Gli2

3) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0 Pain Relevance 0.03

Gli2 and PTHrP expression did not increase for moduli above 1 GPa.

Gene_expression (expression) of Gli2

4) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.94 Pain Relevance 0

Mechanical signals induced by substrate rigidity regulate the expression of Gli2 and PTHrP though ROCK.

Gene_expression (expression) of Gli2

5) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.96 Pain Relevance 0.04

Our observation that the expression of Gli2 by tumor cells is regulated by matrix rigidity is consistent with previous studies suggesting that Hh genes are regulated during development by mechanically transduced signals [43], [44].

Gene_expression (expression) of Gli2 associated with cancer

6) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 1.00 Pain Relevance 0.04

To further explore the Hedgehog-Gli signaling pathway to discriminate between groups A and B, we tested the expression of six additional genes involved in this pathway (DHH, SHH, GLI1, GLI2, GLI3, and GLI4) in three high IHH-expressing percutaneous normal liver samples and three low IHH-overexpressing surgical nontumoral liver samples.

Gene_expression (expression) of GLI2 in liver

7) Confidence 0.37 Published 2008 Journal Hepatology (Baltimore, Md.) Section Body Doc Link PMC2816363 Disease Relevance 0.63 Pain Relevance 0.03

We found that blebbistatin blocked the ability of TGF-ß to stimulate Gli2 and PTHrP expression.

Gene_expression (expression) of Gli2

8) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.20 Pain Relevance 0.05

mediates the effects of substrate rigidity on Gli2 and PTHrP expression through ROCK

Gene_expression (expression) of Gli2

9) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.08 Pain Relevance 0.03

We next investigated whether blocking ROCK inhibits the effects of exogenous TGF-ß on the stimulation of Gli2 and PTHrP expression by treating cells with TGF-ß and inhibiting mechanotransduction with blebbistatin (Figure 6A and B) or Y27632 (Figure 6C and D).

Gene_expression (expression) of Gli2 associated with mechanotransduction

10) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.12 Pain Relevance 0.05

Furthermore, inhibition of tumor cell actomyosin contractility in both pharmacological and genetic models decreased Gli2 and PTHrP expression.

Gene_expression (expression) of Gli2 associated with cancer

11) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.99 Pain Relevance 0.03

Expression of Gli2, a transcription factor known to regulate PTHrP [4], also showed a 5-fold increase on hard substrates in both MDA-MB-231 and RWGT2 (Figure 3) but not in MCF-7 cells (data not shown).

Gene_expression (Expression) of Gli2 in MDA-MB-231

12) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2981576 Disease Relevance 0.25 Pain Relevance 0

Several promising cancer drugs that reduce medulloblastoma growth in mouse models purportedly interfere with Gli1 and Gli2 expression by blocking the signalling pathway downstream of Smo.

Gene_expression (expression) of Gli2 associated with cancer and medulloblastoma

13) Confidence 0.29 Published 2007 Journal BMC Syst Biol Section Body Doc Link PMC1839891 Disease Relevance 0.58 Pain Relevance 0

in THP1 macrophages.

Gene_expression (macrophages) of THP1 in macrophages

14) Confidence 0.17 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908545 Disease Relevance 1.26 Pain Relevance 0

Like THP1 macrophages, normal peripheral blood monocytes restored the MMP and prevented activation of caspase 8 and cleavage of PARP in TRAIL-treated tumor cells (data not shown, Figure S2), which is consistent with the ability of colon cancer cells to induce IL-1?

Gene_expression (macrophages) of THP1 in cleavage associated with cancer and colon cancer

15) Confidence 0.17 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908545 Disease Relevance 1.01 Pain Relevance 0

Remarkably, the presence of THP1 macrophages or treatment with IL-1?

Gene_expression (macrophages) of THP1 in macrophages

16) Confidence 0.17 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908545 Disease Relevance 0.80 Pain Relevance 0.05

Moreover, they inhibited chemotaxis, phagocytosis of Escherichia coli and PMA-stimulated production of hydrogen peroxide in THP-1 differentiated to macrophage-like cells.

Gene_expression (production) of THP-1 in THP-1

17) Confidence 0.15 Published 2002 Journal Scand. J. Immunol. Section Abstract Doc Link 12193227 Disease Relevance 0 Pain Relevance 0.15

In this study we evaluated the effect of several NSAIDs on COX-1 and COX-2 mRNA, protein expression and PGE2 production in PMA-differentiated THP-1 and U937 human macrophages stimulated with LPS.

Gene_expression (production) of THP-1 in macrophages associated with cinod

18) Confidence 0.15 Published 1996 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 8780708 Disease Relevance 0.16 Pain Relevance 0.39

In this study we evaluated the effect of several NSAIDs on COX-1 and COX-2 mRNA, protein expression and PGE2 production in PMA-differentiated THP-1 and U937 human macrophages stimulated with LPS.

Gene_expression (expression) of THP-1 in macrophages associated with cinod

19) Confidence 0.15 Published 1996 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 8780708 Disease Relevance 0.17 Pain Relevance 0.40

Successful transfection with the inhibitory sequence was confirmed by a downregulation of survivin expression in THP-1 lysates as assessed by ELISA.

Gene_expression (expression) of THP-1 in THP-1

20) Confidence 0.08 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065333 Disease Relevance 0.27 Pain Relevance 0.14

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