INT278361

Context Info Confidence 0.41 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 6 Disease Relevance 0.63 Pain Relevance 0.15

signal transduction (Lyn) Golgi apparatus (Lyn) plasma membrane (Lyn) nucleus (Lyn) enzyme binding (Lyn) kinase activity (Lyn)

Anatomy Link Frequency C8-B4 2 Lyn (Mus musculus)

Pain Link Frequency Relevance Heat Potency 26 92.08 Glutamate 2 75.16 gABA 2 74.36 imagery 14 63.96 rheumatoid arthritis 1 24.64 cytokine 13 9.76 antidepressant 70 5.00 Endep 32 5.00 Neuropathic pain 18 5.00 antagonist 12 5.00

Disease Link Frequency Relevance Heat Fever 9 77.48 Colitis 1 76.68 Cytomegalovirus Infection 1 75.80 Pneumonia 1 75.60 Pleural Effusion 20 75.08 Lymphocytosis 2 70.92 Cancer 17 58.88 Leukemia 39 50.00 Systemic Lupus Erythematosus 1 47.96 Myeloid Leukemia 197 46.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Other mechanisms of imatinib resistance may include: increased expression of Bcr-Abl through genomic amplification (Nicolini et al 2006), overexpression of Lyn or other Src-family tyrosine kinases (Donato et al 2003; Dai et al 2004), or overexpression of drug efflux proteins such as P-glycoprotein, which may decrease the intracellular concentration of imatinib in leukemic cells (Thomas et al 2004).

Positive_regulation (increased) of Gene_expression (overexpression) of Lyn

1) Confidence 0.41 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0.06 Pain Relevance 0

Other mechanisms of imatinib resistance may include: increased expression of Bcr-Abl through genomic amplification (Nicolini et al 2006), overexpression of Lyn or other Src-family tyrosine kinases (Donato et al 2003; Dai et al 2004), or overexpression of drug efflux proteins such as P-glycoprotein, which may decrease the intracellular concentration of imatinib in leukemic cells (Thomas et al 2004).

Positive_regulation (overexpression) of Gene_expression (overexpression) of Lyn

2) Confidence 0.27 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0.06 Pain Relevance 0

We measured elevated levels of Lyn tyrosine kinase in activated C8-B4 cells.

Positive_regulation (elevated) of Gene_expression (levels) of Lyn tyrosine kinase in C8-B4

3) Confidence 0.25 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.11

Altogether, these results reveal that Lyn/Syk activation following Hz exposure initiates the PI3K and ERK signaling pathways and these pathways appear to regulate the production of mature IL-1?.

Positive_regulation (activation) of Gene_expression (exposure) of Lyn

4) Confidence 0.24 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2722371 Disease Relevance 0 Pain Relevance 0

Copy number for each molecule (all P2X subunits and Lyn tyrosine kinase) was determined based on comparisons to standard curves, and for each sample, the copy number for each molecule was normalized to the expression of the endogenous housekeeping gene hypoxanthine phosphoribosyl transferase (HPRT).

Positive_regulation (normalized) of Gene_expression (expression) of Lyn tyrosine kinase

5) Confidence 0.18 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0

These include upregulation of the ABCB1 or ABCG2 drug efflux pumps,58,63,64 downregulation of human organic cation transporter 1 (hOCT1) drug influx transporters,65,66 overexpression of Lyn, a Src-family kinase,67 and other Bcr-Abl-independent mechanisms.

Positive_regulation (overexpression) of Gene_expression (overexpression) of Lyn

6) Confidence 0.18 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.52 Pain Relevance 0.05

General Comments

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