INT117002

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Context Info
Confidence 0.58
First Reported 2004
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 16
Total Number 16
Disease Relevance 9.72
Pain Relevance 1.00

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RNA binding (Sfpi1) nucleus (Sfpi1) DNA binding (Sfpi1)
Anatomy Link Frequency
blood 2
spleen 2
osteoclasts 1
eosinophil 1
Sfpi1 (Mus musculus)
Pain Link Frequency Relevance Heat
fibrosis 11 99.42 Very High Very High Very High
opioid receptor 12 97.20 Very High Very High Very High
cytokine 49 89.08 High High
Opioid 2 82.00 Quite High
imagery 46 80.88 Quite High
mu opioid receptor 1 75.00 Quite High
Inflammatory response 26 71.76 Quite High
Inflammation 110 67.76 Quite High
Pain 8 43.92 Quite Low
metalloproteinase 1 39.28 Quite Low
Disease Link Frequency Relevance Heat
Injury 163 99.76 Very High Very High Very High
Targeted Disruption 12 99.52 Very High Very High Very High
Leukemia 281 99.44 Very High Very High Very High
Fibrosis 14 99.42 Very High Very High Very High
Cancer 325 98.48 Very High Very High Very High
Apoptosis 88 97.80 Very High Very High Very High
Fibromyalgia 4 97.04 Very High Very High Very High
Hypereosinophilic Syndrome 31 96.40 Very High Very High Very High
Breast Cancer 15 90.36 High High
Disease 55 81.76 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The percentages of G1R2 cells varied from 0 to 100% (Fig. 2), but cells with 2 red and 0 green signals, i.e. with the loss of both PU.1 signals, were not observed.
Negative_regulation (loss) of PU.1
1) Confidence 0.58 Published 2008 Journal Mol Cytogenet Section Body Doc Link PMC2572613 Disease Relevance 0.46 Pain Relevance 0
Cells with the loss of one copy of PU.1 can be counted the day after blood sampling; blood smear preparation, FISH hybridization, washing, and microscopic observation require 1 hour, overnight, 3 hours, and a few hours, respectively.
Negative_regulation (loss) of PU.1 in blood
2) Confidence 0.58 Published 2008 Journal Mol Cytogenet Section Body Doc Link PMC2572613 Disease Relevance 0.23 Pain Relevance 0
Among mice that were tentatively diagnosed with ML by clinical findings and blood smear examination, 85% carried spleen cells showing the loss of PU.1 although the frequency of these abnormal cells varied among individuals.
Negative_regulation (loss) of PU.1 in blood associated with leukemia
3) Confidence 0.43 Published 2008 Journal Mol Cytogenet Section Abstract Doc Link PMC2572613 Disease Relevance 1.38 Pain Relevance 0
Some neutron-irradiated mice had cells showing translocated PU.1, although no pathological features differentiated these ML mice from ML mice expressing the simple loss of PU.1.
Negative_regulation (loss) of PU.1 associated with leukemia
4) Confidence 0.43 Published 2008 Journal Mol Cytogenet Section Abstract Doc Link PMC2572613 Disease Relevance 1.30 Pain Relevance 0
Mice with very low frequencies of cells showing the loss of one copy of PU.1 (one-PU.1 frequency) were later diagnosed pathologically not with ML but with blastic or eosinophilic leukemia.
Negative_regulation (loss) of PU.1 associated with leukemia and hypereosinophilic syndrome
5) Confidence 0.43 Published 2008 Journal Mol Cytogenet Section Abstract Doc Link PMC2572613 Disease Relevance 1.38 Pain Relevance 0
As a result, the frequency of cells showing the loss of one copy of PU.1 obtained by this method was very close to that from slides prepared traditionally using spleen cells, and this new method was useful for the rapid diagnosis of the detailed classification of ML in living mice.
Negative_regulation (loss) of PU.1 in spleen associated with leukemia
6) Confidence 0.43 Published 2008 Journal Mol Cytogenet Section Body Doc Link PMC2572613 Disease Relevance 0.84 Pain Relevance 0
The FISH method was capable of detecting aberration of copy number of the PU.1 gene on murine chromosome 2, and using a peripheral blood smear is more practical and less invasive than conventional pathological diagnosis or the cytogenetic examination of spleen cells.



Negative_regulation (number) of PU.1 in spleen
7) Confidence 0.43 Published 2008 Journal Mol Cytogenet Section Abstract Doc Link PMC2572613 Disease Relevance 0.90 Pain Relevance 0
Mice with homozygous PU.1 deficiency have osteopetrotic bones due to the lack of osteoclasts that would form from the myeloid lineage [19].


Negative_regulation (deficiency) of PU.1 in osteoclasts
8) Confidence 0.42 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592787 Disease Relevance 0.22 Pain Relevance 0
When the PU.1 gene is disrupted as in PU.1 knock-out mice and using small interfering RNA-based strategy in RAW264.7 cells, the transcription of the endogenous target MOR gene is increased significantly.
Negative_regulation (disrupted) of PU.1 associated with targeted disruption and opioid receptor
9) Confidence 0.42 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 14998994 Disease Relevance 0.24 Pain Relevance 0.64
In addition, high levels of PU.1 lead to an increase in myeloid differentiation.3 In most cells, PU.1 antagonizes GATA-1 (a zinc finger family member), the latter of which has synergistic activity in regulating eosinophil lineage specification and eosinophil granule protein transcription.4 The interferon consensus sequence binding protein (ICSBP) is also a key transcription factor for eosinophils and is demonstrated by a loss of eosinophils in ICSBP-deficient mice.5 Of these transcription factors, GATA-1 is clearly the most important for eosinophil lineage specification, based on loss of the eosinophil lineage in mice harboring a targeted deletion of the high affinity GATA-binding site in the GATA-1 promoter,6 and based on eosinophil differentiation experiments in vitro.7
Negative_regulation (levels) of PU.1 in eosinophil
10) Confidence 0.41 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2846745 Disease Relevance 0.08 Pain Relevance 0
1 mRNA, previously implicated in several fibrosis scenarios, is significantly reduced in PU.1 null wounds, as revealed by RNase protection analyses [6].
Negative_regulation (reduced) of PU.1 associated with fibrosis and injury
11) Confidence 0.38 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 1.16 Pain Relevance 0.32
Examples of each class include pertuzumab and trastuzumab (which block dimerization and suppress signaling by binding to extracellular domains II and IV, respectively); the HER2/neu TK-inhibitor lapatinib; and Hsp90 inhibitors including geldanamycin derivatives, SNX-5422, NVP-AUY922, BIIB021 and PU-H71.[7], [11]–[18]
Negative_regulation (inhibitors) of PU-H71
12) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.59 Pain Relevance 0.04
Furthermore, unlike other trastuzumab constructs radiolabeled with shorter-lived nuclides, 89Zr-DFO-trastuzumab may be used to measure the long-term pharmacodynamic effects and potentially patient response to treatment using Hsp90 inhibitors including PU-H71.
Negative_regulation (inhibitors) of PU-H71
13) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.15 Pain Relevance 0
The results demonstrate 89Zr-radiolabeled trastuzumab has the potential to be used in the clinic as a radiotracer for both localizing and staging of HER2/neu positive tumors, and in the long-term measurements of the efficacy of treatment with Hsp90 inhibitors such as PU-H71 and other drugs with extended pharmacodynamic profiles.


Negative_regulation (inhibitors) of PU-H71 associated with cancer
14) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.16 Pain Relevance 0
Decreased expression levels of RAF1 demonstrate that PU-H71 inhibition of Hsp90 also inhibits the MAPK signaling pathway, consequently suppressing the transcription of genes associated with cell survival, angiogenesis, proliferation, migration, mitosis, and differentiation.
Negative_regulation (inhibition) of PU-H71
15) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.22 Pain Relevance 0
Thus, in comparison with control experiments, PU-H71 inhibition of Hsp90 and degradation of HER2/neu results in approximately 50% decrease in 89Zr-DFO-trastuzumab tumor uptake at 24 and 72 h (Table S2; Control-to-PU-H71-treated %ID/g ratios of 2.17 [P?
Negative_regulation (inhibition) of PU-H71 associated with cancer
16) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.41 Pain Relevance 0

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