INT89404

Context Info Confidence 0.45 First Reported 2000 Last Reported 2010 Negated 3 Speculated 4 Reported most in Body Documents 30 Total Number 33 Disease Relevance 24.47 Pain Relevance 12.71

signal transduction (TNF) extracellular space (TNF) extracellular region (TNF) plasma membrane (TNF) intracellular (TNF) extracellular matrix organization (TNF)

Anatomy Link Frequency spinal 4 nerve 2 muscle 2 heart 2 TNF (Homo sapiens)

Pain Link Frequency Relevance Heat Pain 100 100.00 Nerve growth factor 8 100.00 rheumatoid arthritis 619 99.92 spinal inflammation 18 99.84 Sciatica 7 99.52 withdrawal 10 99.12 Inflammation 249 98.96 cytokine 202 98.52 Etanercept 161 98.52 Sicca syndrome 80 98.04

Disease Link Frequency Relevance Heat Cancer 135 100.00 Necrosis 122 100.00 Infection 34 100.00 Rheumatoid Arthritis 625 99.92 Systemic Lupus Erythematosus 192 99.84 Pain 109 99.84 Low Back Pain 24 99.84 Fistula 3 99.84 Cv General 4 Under Development 195 99.80 Nerve Root Compression 8 99.52

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

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Disease term

[Efficacy of tumor necrosis factor-alpha blockade for severe sciatica?].

Regulation ([Efficacy) of Negative_regulation (blockade) of tumor necrosis factor-alpha associated with necrosis, cancer and sciatica

1) Confidence 0.45 Published 2004 Journal Rev Med Suisse Romande Section Title Doc Link 15552747 Disease Relevance 0.99 Pain Relevance 0.53

Understanding the role of tumor necrosis factor inhibition in ankylosing spondylitis.

Regulation (role) of Negative_regulation (inhibition) of tumor necrosis factor associated with spinal inflammation, necrosis and cancer

2) Confidence 0.45 Published 2005 Journal Semin. Arthritis Rheum. Section Title Doc Link 15692960 Disease Relevance 0.77 Pain Relevance 0.57

TNFalpha blockade, however, is a treatment, rather than a cure, and is not effective in all patients or in all autoimmune diseases and further research is needed to get closer to a cure.

Neg (not) Regulation (effective) of Negative_regulation (blockade) of TNFalpha associated with autoimmune disease

3) Confidence 0.44 Published 2007 Journal Curr Opin Pharmacol Section Abstract Doc Link 17627887 Disease Relevance 0.87 Pain Relevance 0.39

antibodies resulted in suppression of not only TNF-?

Regulation (resulted) of Negative_regulation (suppression) of TNF

4) Confidence 0.44 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661661 Disease Relevance 1.23 Pain Relevance 0.65

It may therefore be possible that under these experimental conditions, a salicylic acid-mediated mechanism is responsible for the inhibition of TNF?

Regulation (responsible) of Negative_regulation (inhibition) of TNF

5) Confidence 0.44 Published 2008 Journal J Inflamm (Lond) Section Body Doc Link PMC2525633 Disease Relevance 0.19 Pain Relevance 0.25

Rationale for using tumor necrosis factor inhibition to treat systemic lupus erythematosus

Regulation (using) of Negative_regulation (inhibition) of tumor necrosis factor associated with necrosis, cancer and systemic lupus erythematosus

6) Confidence 0.43 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374473 Disease Relevance 1.58 Pain Relevance 0.33

The recent introduction of tumor necrosis factor (TNF) blockers in the treatment of spondyloarthritis has offered the most hope in not only relieving symptoms and signs of both peripheral arthritis and enthesitis but also spinal disease, which often has been refractory to other agents.

Regulation (introduction) of Negative_regulation (blockers) of TNF in spinal associated with necrosis, spinal diseases, cancer and arthritis

7) Confidence 0.43 Published 2005 Journal Am. J. Med. Section Abstract Doc Link 15922688 Disease Relevance 1.02 Pain Relevance 0.38

The recent introduction of tumor necrosis factor (TNF) blockers in the treatment of spondyloarthritis has offered the most hope in not only relieving symptoms and signs of both peripheral arthritis and enthesitis but also spinal disease, which often has been refractory to other agents.

Regulation (introduction) of Negative_regulation (blockers) of tumor necrosis factor in spinal associated with necrosis, spinal diseases, cancer and arthritis

8) Confidence 0.43 Published 2005 Journal Am. J. Med. Section Abstract Doc Link 15922688 Disease Relevance 1.02 Pain Relevance 0.38

SUMMARY: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.

Regulation (introduction) of Negative_regulation (inhibitors) of tumor necrosis factor

9) Confidence 0.42 Published 2006 Journal Curr Opin Rheumatol Section Body Doc Link 16763453 Disease Relevance 0.25 Pain Relevance 0

Although more research is needed on the potential role for TNF-alpha inhibition of insulin action, elevated TNF-alpha production after muscle damage may impair insulin signal transduction.

Regulation (role) of Negative_regulation (inhibition) of TNF-alpha in muscle

10) Confidence 0.33 Published 2000 Journal Am. J. Physiol. Endocrinol. Metab. Section Abstract Doc Link 10893341 Disease Relevance 0.28 Pain Relevance 0.03

plays an important role in host defence against infection, inhibition of TNF-?

Regulation (role) of Negative_regulation (inhibition) of TNF associated with infection

11) Confidence 0.33 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936291 Disease Relevance 1.55 Pain Relevance 0.51

Although the evidence for therapeutic efficacy of TNF blockade in SLE is still limited, there are a minimum of 28 cases reported at least in abstract form [56-61] and most of these are on the use of the chimeric monoclonal antibody infliximab.

Regulation (efficacy) of Negative_regulation (blockade) of TNF associated with infliximab and systemic lupus erythematosus

12) Confidence 0.26 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374473 Disease Relevance 1.25 Pain Relevance 0.26

The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis.

Regulation (effect) of Negative_regulation (blockade) of tumor necrosis factor associated with spinal inflammation, necrosis, cancer and rheumatoid arthritis

13) Confidence 0.24 Published 2004 Journal Semin. Arthritis Rheum. Section Title Doc Link 14978666 Disease Relevance 0.49 Pain Relevance 0.28

Clinical studies of TNF inhibitors and congestive heart failure

Regulation (studies) of Negative_regulation (inhibitors) of TNF in heart associated with cv general 4 under development

14) Confidence 0.23 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257451 Disease Relevance 1.87 Pain Relevance 0.73

For patients who do not respond to tumor necrosis factor blockade, several treatment options are under study.

Neg (not) Regulation (respond) of Negative_regulation (blockade) of tumor necrosis factor

15) Confidence 0.22 Published 2005 Journal Curr Opin Rheumatol Section Body Doc Link 15838232 Disease Relevance 0 Pain Relevance 0

The differences between the effects of TNF blockade on IFN response activity between the studies in SS [11] and SoJIA [9], on the one hand, and our studies in RA and spondyloarthritis (SpA) [31], on the other, could have their origin in differences in design between the studies, such as the use of infliximab in RA versus etanercept in SS, and the different readout systems used.

Regulation (effects) of Negative_regulation (blockade) of TNF associated with infliximab, sicca syndrome, rheumatoid arthritis and etanercept

16) Confidence 0.21 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875639 Disease Relevance 0.87 Pain Relevance 0.45

Therefore, the relationship between the extent of the baseline IFN response gene expression levels and its change after TNF blockade was tested.

Regulation (change) of Negative_regulation (blockade) of TNF

17) Confidence 0.21 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875639 Disease Relevance 0.40 Pain Relevance 0.25

However, the regulation of IFN response genes upon TNF blockade was highly variable between patients.

Regulation (regulation) of Negative_regulation (blockade) of TNF

18) Confidence 0.15 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875639 Disease Relevance 0.60 Pain Relevance 0.36

The mechanisms responsible for the differential effects of TNF?

Regulation (responsible) of Negative_regulation (effects) of TNF

19) Confidence 0.15 Published 2010 Journal Respir Res Section Body Doc Link PMC2922094 Disease Relevance 0.19 Pain Relevance 0.28

and p38 phosphorylation; treatment with inhibitors of either TNF-?

Regulation (treatment) of Negative_regulation (inhibitors) of TNF

20) Confidence 0.12 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2861665 Disease Relevance 0.88 Pain Relevance 0.65

General Comments

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