INT88718

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Context Info
Confidence 0.58
First Reported 1999
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 11
Total Number 18
Disease Relevance 12.98
Pain Relevance 0.84

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

signal transduction (Erbb2) plasma membrane (Erbb2) nucleus (Erbb2)
kinase activity (Erbb2) cytoplasm (Erbb2)
Anatomy Link Frequency
A549 2
cardiomyocytes 1
immune cells 1
BT-474 1
Erbb2 (Mus musculus)
Pain Link Frequency Relevance Heat
COX2 4 100.00 Very High Very High Very High
Central nervous system 80 99.16 Very High Very High Very High
anesthesia 12 95.92 Very High Very High Very High
positron emission tomography 65 88.16 High High
agonist 8 72.80 Quite High
cINOD 2 58.56 Quite High
imagery 17 57.56 Quite High
Pain 3 25.00 Low Low
cytokine 1 25.00 Low Low
isoflurane 10 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Hyperplasia 5 100.00 Very High Very High Very High
Cancer 440 99.96 Very High Very High Very High
Myocardial Infarction 5 99.92 Very High Very High Very High
Targeted Disruption 8 99.16 Very High Very High Very High
Metastasis 63 99.00 Very High Very High Very High
Breast Cancer 109 98.36 Very High Very High Very High
Advanced Or Metastatic Breast Cancer 34 98.00 Very High Very High Very High
Dilated Cardiomyopathy 3 97.80 Very High Very High Very High
Adenocarcinoma 11 97.76 Very High Very High Very High
Immunotherapy Of Cancer 8 97.28 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In addition, HER-2 downregulation appears to shut down HER-2 initiated MAP kinase pathways and makes other ER-linked apoptotic pathways dominant [40].
Negative_regulation (downregulation) of HER-2 associated with apoptosis
1) Confidence 0.58 Published 2008 Journal Int Semin Surg Oncol Section Body Doc Link PMC2383915 Disease Relevance 0.27 Pain Relevance 0.07
Previous studies have shown that EGFR or HER-2 inhibition may potentiate the effect of radiation therapy [10].
Negative_regulation (inhibition) of HER-2
2) Confidence 0.52 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 0.69 Pain Relevance 0.08
Since inhibition of EGFR and HER-2 has been shown to reduce angiogenesis through an indirect effect on VEGF production [11,12], we evaluated whether lapatinib interferes with tumor angiogenesis in the A549 model in vivo.
Negative_regulation (inhibition) of HER-2 in A549 associated with cancer
3) Confidence 0.52 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 0.73 Pain Relevance 0.07
Lapatinib may have a therapeutic advantage over erlotinib because it acts as a dual inhibitor of EGFR (or HER-1) and HER-2 (ErbB2) tyrosine kinases.
Negative_regulation (inhibitor) of HER-2
4) Confidence 0.52 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 1.13 Pain Relevance 0
Lapatinib may have a therapeutic advantage over erlotinib because it acts as a dual inhibitor of EGFR (or HER-1) and HER-2 (ErbB2) tyrosine kinases.
Negative_regulation (inhibitor) of ErbB2
5) Confidence 0.52 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 1.13 Pain Relevance 0
Two main methods exist for the determination of HER2 gene amplification and protein expression in breast cancer specimens, fluorescence in situ hybridisation or FISH (direct or indirect) and IHC.
Negative_regulation (determination) of HER2 gene associated with breast cancer
6) Confidence 0.42 Published 2008 Journal Int Semin Surg Oncol Section Body Doc Link PMC2383915 Disease Relevance 1.15 Pain Relevance 0
A possible explanation for these observations could be a predilection of HER2/neu tumors to developed CNS metastases.
Negative_regulation (predilection) of HER2/neu associated with cancer, central nervous system and metastasis
7) Confidence 0.42 Published 2006 Journal Breast Cancer Res Section Body Doc Link PMC1779464 Disease Relevance 1.40 Pain Relevance 0.28
The approximate 3-fold decrease in BT-474 T/M ratios between the vehicle-treated and PU-H71 treated mice is consistent with the decrease in HER2/neu expression levels observed by in vivo Western blots (Figure 4).
Negative_regulation (decrease) of HER2/neu in BT-474
8) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2810330 Disease Relevance 0.65 Pain Relevance 0.03
It is a mouse-human chimeric antibody that produces anti-tumor effects by blocking the HER2-neu receptor, and can also interact with human immune cells to effect antibody dependent cell-mediated cytotoxicity.
Negative_regulation (blocking) of neu in immune cells associated with cancer
9) Confidence 0.41 Published 1999 Journal Cancer Biother. Radiopharm. Section Abstract Doc Link 10850281 Disease Relevance 0.54 Pain Relevance 0
Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer.
Negative_regulation (inhibitor) of HER-2 associated with advanced or metastatic breast cancer
10) Confidence 0.38 Published 2010 Journal BMC Cancer Section Abstract Doc Link PMC2883966 Disease Relevance 0.71 Pain Relevance 0
Lapatinib is a novel dual EGFR and HER-2 tyrosine kinase inhibitor that is now approved by the FDA for treatment of metastatic breast cancers with overexpression of HER-2 receptors [20-22].
Negative_regulation (inhibitor) of HER-2 associated with advanced or metastatic breast cancer
11) Confidence 0.38 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 0.78 Pain Relevance 0
However, 21% of the nuclei exhibited HER-2 gene amplification as shown by four red HER-2 signals and two green centromeric signals.
Negative_regulation (exhibited) of HER-2 gene
12) Confidence 0.38 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 0.12 Pain Relevance 0
As a result, hErbB-1-mut was expressed selectively in cardiomyocytes leading to the blockade of endogenous ErbB-1 phosphorylation and ErbB-2 transphosphorylation.
Negative_regulation (blockade) of ErbB-2 in cardiomyocytes
13) Confidence 0.35 Published 2008 Journal Am. J. Physiol. Heart Circ. Physiol. Section Abstract Doc Link 18599591 Disease Relevance 0.46 Pain Relevance 0.10
Blockade of ErbB-2 or ErbB-4 tyrosine kinase receptor signaling leads to dilated cardiomyopathy.
Negative_regulation (Blockade) of ErbB-2 associated with dilated cardiomyopathy
14) Confidence 0.35 Published 2008 Journal Am. J. Physiol. Heart Circ. Physiol. Section Abstract Doc Link 18599591 Disease Relevance 0.38 Pain Relevance 0
In conclusion, these observations indicate that the blockade of cardiac ErbB-1 signaling leads to the blockade of ErbB-2 signaling and that together they result in cardiac dysfunction.
Negative_regulation (blockade) of ErbB-2
15) Confidence 0.35 Published 2008 Journal Am. J. Physiol. Heart Circ. Physiol. Section Abstract Doc Link 18599591 Disease Relevance 0.14 Pain Relevance 0.06
As expected, lapatinib reduced levels of p-EGFR, p-HER-2, and p-ERK1/2 in A549 cells.
Negative_regulation (reduced) of p-HER-2 in A549
16) Confidence 0.33 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2883966 Disease Relevance 0.43 Pain Relevance 0
HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice.
Negative_regulation (reduced) of HER2/neu-induced associated with targeted disruption and cox2
17) Confidence 0.12 Published 2005 Journal Cancer Res. Section Title Doc Link 16267038 Disease Relevance 1.09 Pain Relevance 0.10
HER2/neu-induced mammary hyperplasia was also substantially reduced in Cox-2 null mice.
Negative_regulation (reduced) of HER2/neu-induced associated with hyperplasia
18) Confidence 0.12 Published 2005 Journal Cancer Res. Section Abstract Doc Link 16267038 Disease Relevance 1.18 Pain Relevance 0.06

General Comments

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