INT125320

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Context Info
Confidence 0.45
First Reported 2005
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 20
Total Number 32
Disease Relevance 23.93
Pain Relevance 1.42

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) small molecule metabolic process (HSP90AA1) intracellular (HSP90AA1)
response to stress (HSP90AA1) cytoplasm (HSP90AA1) cytosol (HSP90AA1)
Anatomy Link Frequency
colon 9
BT-474 3
HSP90AA1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Morphine 6 98.60 Very High Very High Very High
cINOD 26 96.56 Very High Very High Very High
fluoxetine 1 93.60 High High
antidepressant 1 92.56 High High
COX-2 inhibitor 24 92.48 High High
agonist 1 91.00 High High
Pain 2 89.44 High High
Opioid 1 86.76 High High
Potency 37 84.60 Quite High
antagonist 25 83.20 Quite High
Disease Link Frequency Relevance Heat
Shock 212 100.00 Very High Very High Very High
Gastrointestinal Stromal Tumor 104 99.84 Very High Very High Very High
Cancer 1677 99.80 Very High Very High Very High
Colon Cancer 641 99.70 Very High Very High Very High
Breast Cancer 527 98.96 Very High Very High Very High
Leukemia 3 98.56 Very High Very High Very High
Metastasis 176 97.64 Very High Very High Very High
INFLAMMATION 27 95.84 Very High Very High Very High
Pancreatic Cancer 24 95.80 Very High Very High Very High
Carcinoma 61 95.72 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Combined inhibition of extracellular signal-regulated kinases and HSP90 sensitizes human colon carcinoma cells to ionizing radiation.
Negative_regulation (inhibition) of HSP90 in colon associated with colon cancer
1) Confidence 0.45 Published 2005 Journal Oncogene Section Title Doc Link 15735687 Disease Relevance 0.28 Pain Relevance 0.10
Therefore, tumor cells with elevated ERK1/2 activity can be effectively sensitized to radiation treatment by a combinational inhibition of HSP90 and MAPK activity.
Negative_regulation (inhibition) of HSP90 associated with cancer
2) Confidence 0.45 Published 2005 Journal Oncogene Section Abstract Doc Link 15735687 Disease Relevance 0.22 Pain Relevance 0
Hence, results from this study suggest that ATF3 functions as a tumor suppressor and anti-metastatic factor in HCT116 colon cancer, which is therapeutically inducible by blocking Hsp90.
Negative_regulation (blocking) of Hsp90 in colon associated with cancer and colon cancer
3) Confidence 0.35 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 1.70 Pain Relevance 0
To further validate these results, we investigated whether blocking Hsp90 also leads to ATF3 up-regulation in other human cancer cell types.
Spec (whether) Negative_regulation (blocking) of Hsp90 associated with cancer
4) Confidence 0.35 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 0.62 Pain Relevance 0
Our recent observation that Hsp90 inhibition induces ATF3 in cancer cells and the lack of clarity regarding the biological effect of this transcription factor in oncology pressed our aim to define the role of ATF3 in colon cancer.
Negative_regulation (inhibition) of Hsp90 in colon associated with cancer and colon cancer
5) Confidence 0.35 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 1.54 Pain Relevance 0
Here, we report that treatment of cells with geldanamycin, an inhibitor of heat shock protein 90 (Hsp90), led to effective attenuation of morphine-induced adenylate cyclase sensitization.
Negative_regulation (inhibitor) of Hsp90 associated with shock and morphine
6) Confidence 0.34 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20100459 Disease Relevance 0.36 Pain Relevance 0.52
However, although ERBB2 is an excellent client protein, ERBB2-negative tumors may well be driven by susceptible client proteins and respond to HSP90 inhibitors.
Negative_regulation (inhibitors) of HSP90 associated with cancer
7) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.71 Pain Relevance 0.03
Thus, even though 8 mg/kg NVP-AUY922 appeared to cause a slight reduction in HSP90-p23 complexes, the remaining complexes are likely sufficient to maintain downstream signaling as evidenced by AKT phosphorylation.


Negative_regulation (reduction) of HSP90-p23
8) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.43 Pain Relevance 0
These data suggest that complete inhibition of HSP90 is not needed to achieve antiproliferative effect by continuous exposure.
Negative_regulation (inhibition) of HSP90
9) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.52 Pain Relevance 0.04
We have previously shown NVP-AUY922 to be a potent selective inhibitor of HSP90.
Negative_regulation (inhibitor) of HSP90
10) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.96 Pain Relevance 0.03
The biodistribution and pharmacokinetic profile of NVP-AUY922 in the BT-474 xenograft model encouraged us to assess whether NVP-AUY922 is capable of directly interfering with the catalytic cycle of HSP90 with concomitant depletion of HSP90 client proteins in vivo (Figure 2b).
Negative_regulation (depletion) of HSP90 in BT-474
11) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.23 Pain Relevance 0
This method, however, does not directly demonstrate that the catalytic activity of HSP90 has been blocked.
Negative_regulation (blocked) of HSP90
12) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.25 Pain Relevance 0
We observed that the inhibition of HSP90 by a single dose of NVP-AUY922 was paralleled by reductions in phospho-AKT levels.
Negative_regulation (inhibition) of HSP90
13) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.28 Pain Relevance 0
Destabilization of the HSP90-p23 interaction in tumor cells and the subsequent measurement using immunoprecipitation therefore can be used to monitor the effect of HSP90 inhibitors on the HSP90 catalytic cycle (Figure 1b).
Negative_regulation (inhibitors) of HSP90 associated with cancer
14) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.10 Pain Relevance 0.04
In BT-474 cells, NVP-AUY922 and 17-AAG caused a concentration-dependent decrease in the amount of HSP90?
Negative_regulation (decrease) of HSP90 in BT-474
15) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.09 Pain Relevance 0.04
The antitumor effect of 17-AAG has been thoroughly evaluated in this model, which is known to be highly sensitive to HSP90 inhibitors when grown as subcutaneous (s.c.) xenograft tumors [21,30].
Negative_regulation (inhibitors) of HSP90 associated with cancer
16) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.28 Pain Relevance 0
BT-474 and SKBr3 have often been used to examine the effects of HSP90 inhibitors in high ERBB2 expressing breast cancer cell lines.
Spec (examine) Negative_regulation (inhibitors) of HSP90 in BT-474 associated with breast cancer
17) Confidence 0.26 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2397535 Disease Relevance 0.50 Pain Relevance 0.03
We previously observed that treatment of HCT116 and SW620 colon cancer cells with an Hsp90 inhibitor (17-DMAG) substantially up-regulates constitutive ATF3 expression [8].
Negative_regulation (inhibitor) of Hsp90 in colon associated with colon cancer
18) Confidence 0.26 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 0.65 Pain Relevance 0
The results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in various cancer cells, including colon, gastric and pancreatic cancer.
Negative_regulation (inhibition) of Hsp90 in colon associated with cancer and pancreatic cancer
19) Confidence 0.26 Published 2010 Journal BMC Cancer Section Abstract Doc Link PMC3003660 Disease Relevance 2.12 Pain Relevance 0.04
Importantly, and of high clinical relevance, we could show in the current and in one preliminary previous study that ATF3 expression can be induced in cancer cells by Hsp90 inhibition in vitro and in vivo.
Negative_regulation (inhibition) of Hsp90 associated with cancer
20) Confidence 0.26 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 1.19 Pain Relevance 0

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