INT127480

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Context Info
Confidence 0.57
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 20
Total Number 21
Disease Relevance 10.67
Pain Relevance 0.56

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

unfolded protein binding (Hsp90aa1) protein folding (Hsp90aa1) cytosol (Hsp90aa1)
ATPase activity (Hsp90aa1) intracellular (Hsp90aa1) response to stress (Hsp90aa1)
Anatomy Link Frequency
osteoclast 1
Hsp90aa1 (Mus musculus)
Pain Link Frequency Relevance Heat
imagery 120 98.92 Very High Very High Very High
corticosteroid 98 89.44 High High
antagonist 8 89.28 High High
agonist 45 79.52 Quite High
addiction 3 50.00 Quite Low
antidepressant 20 44.88 Quite Low
Pain 6 37.84 Quite Low
positron emission tomography 10 35.76 Quite Low
Neuronal excitability 4 22.72 Low Low
Hippocampus 24 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Shock 180 100.00 Very High Very High Very High
Metastasis 109 99.48 Very High Very High Very High
Cancer 851 98.60 Very High Very High Very High
Synovial Sarcoma 105 98.20 Very High Very High Very High
Apoptosis 75 97.52 Very High Very High Very High
Osteolysis 3 96.68 Very High Very High Very High
Death 14 95.52 Very High Very High Very High
Glioblastoma 198 95.36 Very High Very High Very High
Breast Cancer 37 95.04 Very High Very High Very High
Leukemia 9 94.64 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
These genes included a number of chaperones Hsp90aa1, Hspe1, Hspa4l, Hspd1 and Hsph1.
Negative_regulation (number) of Hsp90aa1
1) Confidence 0.57 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2823686 Disease Relevance 1.22 Pain Relevance 0
Trastuzumab and related mAb-fragments have been radiolabeled with a wide range of radionuclides and quantitative immunoPET imaging has been used to monitor the effect of administering Hsp90 inhibitors on HER2/neu expression levels.[19]–[30] Quantification of changes in HER2/neu expression in response to Hsp90 treatment has the potential to facilitate patient-specific dose regimes.
Negative_regulation (inhibitors) of Hsp90 associated with imagery
2) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.24 Pain Relevance 0.05
Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence caused by 17-AAG in vivo.
Negative_regulation (inhibitors) of HSP90 in osteoclast associated with cancer and osteolysis
3) Confidence 0.40 Published 2005 Journal Cancer Res. Section Abstract Doc Link 15930315 Disease Relevance 0.92 Pain Relevance 0
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 Hsp90
4) Confidence 0.32 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.59 Pain Relevance 0.04
Experiments also revealed that expression levels of Hsp90 remained constant with varying PU-H71 concentrations but Hsp70 levels increased in response to Hsp90 inhibition at concentrations of approximately 0.1–0.25 µM.


Negative_regulation (inhibition) of Hsp90
5) Confidence 0.32 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.37 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 Hsp90
6) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.22 Pain Relevance 0
Changes in the expression levels of HER2/neu in response to Hsp90 inhibition were investigated by in vivo pharmacodynamic (PD) studies.
Negative_regulation (inhibition) of Hsp90
7) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.21 Pain Relevance 0
These studies also showed that, unlike most tyrosine-kinase inhibitors, PU-H71 displays an extended pharmacodynamic profile for Hsp90 inhibition at time points >24 h, and this window of activity is ideal for immunoPET imaging with radioimmunoconjugates such as 89Zr-DFO-trastuzumab.
Negative_regulation (inhibition) of Hsp90 associated with imagery
8) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.23 Pain Relevance 0.05
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 Hsp90 associated with cancer
9) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.41 Pain Relevance 0
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 Hsp90
10) Confidence 0.28 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 Hsp90 associated with cancer
11) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.16 Pain Relevance 0
In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted.


Negative_regulation (inhibitor) of Hsp90 associated with shock
12) Confidence 0.27 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2810330 Disease Relevance 0.27 Pain Relevance 0
Gedunin was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors.
Negative_regulation (inhibition) of Hsp90 associated with shock
13) Confidence 0.25 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.21 Pain Relevance 0.07
Gedunin was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors.
Negative_regulation (inhibitors) of Hsp90 associated with shock
14) Confidence 0.25 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.26 Pain Relevance 0.07
17AAG is an HSP90 inhibitor that is in clinical phase I trials targeting different types of cancers, but its use has not been reported against glioblastoma [19,20,31].
Negative_regulation (inhibitor) of HSP90 associated with glioblastoma and cancer
15) Confidence 0.17 Published 2008 Journal J Transl Med Section Body Doc Link PMC2645376 Disease Relevance 1.27 Pain Relevance 0
We chose here to test the drug, 17AAG, because of its diversity in targeting the destabilization of numerous oncoproteins [52]. 17AAG, a derivative of geldanamycin, an HSP90 inhibitor that has been in clinical trials in patients with advanced cancer [19,20].
Negative_regulation (inhibitor) of HSP90 associated with cancer
16) Confidence 0.17 Published 2008 Journal J Transl Med Section Body Doc Link PMC2645376 Disease Relevance 1.12 Pain Relevance 0.06
antagonistic; Huang et al. reported that pretreatment with the Hsp90 inhibitor
Negative_regulation (inhibitor) of Hsp90
17) Confidence 0.17 Published 2009 Journal Sarcoma Section Body Doc Link PMC2659882 Disease Relevance 0.81 Pain Relevance 0
Hsp90 inhibitors and HDAC inhibitors are able to synergize on synovial sarcoma,
Negative_regulation (inhibitors) of Hsp90 associated with synovial sarcoma
18) Confidence 0.17 Published 2009 Journal Sarcoma Section Body Doc Link PMC2659882 Disease Relevance 0.49 Pain Relevance 0
It has been shown that an HSP90 inhibitor, geldanamycin, can bind to GRP94, inhibit its function, and increase the transcription of ER molecular chaperones [24].
Negative_regulation (inhibitor) of HSP90
19) Confidence 0.16 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2607540 Disease Relevance 0.33 Pain Relevance 0
Hsp90 inhibition results in degradation of its client
Negative_regulation (inhibition) of Hsp90
20) Confidence 0.13 Published 2009 Journal Sarcoma Section Body Doc Link PMC2659882 Disease Relevance 1.13 Pain Relevance 0

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