INT142404

Context Info Confidence 0.77 First Reported 2004 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 18 Total Number 18 Disease Relevance 4.39 Pain Relevance 0.56

cell proliferation (THPO) extracellular space (THPO) extracellular region (THPO)

Anatomy Link Frequency platelet 4 erythrocyte 1 nucleus 1 kidney 1 granulocyte 1 THPO (Homo sapiens)

Pain Link Frequency Relevance Heat agonist 12 100.00 fibrosis 55 91.00 Infliximab 81 87.84 Potency 11 87.08 rheumatoid arthritis 123 80.80 Pain 4 75.00 Bioavailability 11 60.60 Inflammation 27 59.36 addiction 1 53.36 metalloproteinase 2 50.12

Disease Link Frequency Relevance Heat Malignant Neoplastic Disease 56 99.36 Thrombocytopenia 521 98.44 Leukemia 14 98.28 Fibromyalgia 1 96.28 Myelodysplastic Syndromes 55 94.20 Fibrosis 55 91.00 Cancer 25 90.40 Thyroiditis 5 90.24 Myeloid Leukemia 60 86.88 Aphasia 1 85.16

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

These activities of eltrombopag have been shown to be dependent on the expression of TPO receptor.

Gene_expression (expression) of TPO receptor

1) Confidence 0.77 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.06 Pain Relevance 0.07

Physiologic control of TPO production

Gene_expression (production) of TPO

2) Confidence 0.77 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.06 Pain Relevance 0

Malignant hemopoietic cells are known to express TPO receptors and there is a theoretical risk that TPO growth factors may stimulate growth of malignant cells.

Gene_expression (express) of TPO in hemopoietic cells associated with malignant neoplastic disease

3) Confidence 0.77 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 1.43 Pain Relevance 0.10

Laboratory findings were as follow: erythrocyte sedimentation rate 85 mm/h, C-reactive protein 143 mg/L, white cell count of 11 x 10(9)/L (3.0-9.6), TSH 0.10 mU/L (0.27-4.20), fT4 24.2 pmol/L (12-22), fT3 5.5 pmol/L (2.8-7.1) antinuclear antibodies 1:80, antithyreoglobulin antibodies 212 IE/ml (< 100), thyreoglobulin 442 microg/L, anti-TPO normal and TSH receptor antibodies were negative.

Neg (negative) Gene_expression (negative) of TPO in erythrocyte

4) Confidence 0.75 Published 2007 Journal Praxis Section Abstract Doc Link 17330412 Disease Relevance 0.69 Pain Relevance 0.10

Significantly elevated endogenous TPO levels have been observed in disorders in which there is diminished platelet production and therefore reduced TPO clearance, although thrombopoietin levels are typically normal in patients with ITP.

Gene_expression (levels) of thrombopoietin in platelet associated with thrombocytopenia

5) Confidence 0.67 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.10 Pain Relevance 0

Significantly elevated endogenous TPO levels have been observed in disorders in which there is diminished platelet production and therefore reduced TPO clearance, although thrombopoietin levels are typically normal in patients with ITP.

Gene_expression (levels) of TPO in platelet associated with thrombocytopenia

6) Confidence 0.67 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.09 Pain Relevance 0

The TPO receptor is found on megakaryocyte precursor cells, megakaryocytes, and platelets, as well as on stem cells and early bone marrow progenitor cells of all lineages.

Gene_expression (found) of TPO receptor in platelets

7) Confidence 0.67 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0 Pain Relevance 0

Significantly elevated endogenous TPO levels have been observed in disorders in which there is diminished platelet production and therefore reduced TPO clearance, although thrombopoietin levels are typically normal in patients with ITP.

Gene_expression (clearance) of TPO in platelet associated with thrombocytopenia

8) Confidence 0.67 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.10 Pain Relevance 0

However, clinical development of both recombinant TPOs was ultimately discontinued and many of the clinical studies undertaken between 1994 and 1999 remain unpublished.15 Alternative TPO agonists

Gene_expression (development) of TPO associated with agonist

9) Confidence 0.65 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.45 Pain Relevance 0.05

However, clinical development of both recombinant TPOs was ultimately discontinued and many of the clinical studies undertaken between 1994 and 1999 remain unpublished.15 Alternative TPO agonists

Gene_expression (agonists) of TPO associated with agonist

10) Confidence 0.59 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0.32 Pain Relevance 0.05

Detection of anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG) and anti-adrenal (ADA) autoantibodies

Gene_expression (Detection) of TPO in kidney

11) Confidence 0.29 Published 2004 Journal Arthritis Res Ther Section Body Doc Link PMC1064868 Disease Relevance 0.08 Pain Relevance 0.12

The TPO receptor is found on megakaryocyte precursor cells, megakaryocytes, and platelets, as well as on stem cells and early bone marrow progenitor cells of all lineages.

Gene_expression (found) of TPO receptor in precursor cells

12) Confidence 0.23 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0 Pain Relevance 0

The TPO receptor is found on megakaryocyte precursor cells, megakaryocytes, and platelets, as well as on stem cells and early bone marrow progenitor cells of all lineages.

Gene_expression (found) of TPO receptor in megakaryocytes

13) Confidence 0.23 Published 2010 Journal Drug Des Devel Ther Section Body Doc Link PMC2915538 Disease Relevance 0 Pain Relevance 0

The most frequently detected autoantibodies were reactive with TPO, TG and nucleus (in all instances in three patients).

Gene_expression (reactive) of TPO in nucleus

14) Confidence 0.23 Published 2010 Journal Clinical and Developmental Immunology Section Body Doc Link PMC3004381 Disease Relevance 0 Pain Relevance 0.03

In other studies, McGuckin et al demonstrated that culture of cord blood cells that have been depleted of lineage committed cells in a TPO, c-kit, and flt-3 ligand culture express markers of embryonic stem cells including TRA-1–60, TRA-1–81, SSEA-4, SSEA-3 and Oct-4.

Gene_expression (express) of TPO in blood cells

15) Confidence 0.09 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796850 Disease Relevance 0.26 Pain Relevance 0

PU.1 promotes the cell-type-specific expression of the myeloid lineage genes CD11b, CD11c, CD18, the granulocyte colony-stimulating factor (CSF) receptor, the granulocyte–macrophage CSF receptor, and the macrophage CSF receptor (c-fms) via binding to these genes' promoter regions [18].

Gene_expression (expression) of colony-stimulating factor in granulocyte associated with fibromyalgia

16) Confidence 0.02 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592787 Disease Relevance 0.17 Pain Relevance 0.03

We applied TCD and NIRS during baseline conditions and during CO2 reactivity.

Gene_expression (applied) of NIRS

17) Confidence 0.01 Published 2006 Journal J Neuroengineering Rehabil Section Body Doc Link PMC1544341 Disease Relevance 0.58 Pain Relevance 0

Lee YS, Wang TH, Chen ES, Wei ML, Chen LK carried out the microarray experiments.

Gene_expression (carried) of Wei ML

18) Confidence 0.00 Published 2005 Journal BMC Genomics Section Body Doc Link PMC1262710 Disease Relevance 0 Pain Relevance 0

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