INT167085

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Context Info
Confidence 0.57
First Reported 2004
Last Reported 2011
Negated 0
Speculated 2
Reported most in Body
Documents 67
Total Number 70
Disease Relevance 44.60
Pain Relevance 1.48

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

cell proliferation (ERBB2) signal transduction (ERBB2) plasma membrane (ERBB2)
nucleus (ERBB2) cytoplasm (ERBB2)
Anatomy Link Frequency
MCF-7 2
esophagus 1
BT-474 1
salivary gland 1
heart 1
ERBB2 (Homo sapiens)
Pain Link Frequency Relevance Heat
tolerance 35 98.60 Very High Very High Very High
Inflammation 108 96.84 Very High Very High Very High
addiction 48 96.40 Very High Very High Very High
metalloproteinase 8 89.92 High High
Pain 54 85.32 High High
agonist 38 84.72 Quite High
COX2 1 83.92 Quite High
methotrexate 7 83.76 Quite High
antagonist 15 76.92 Quite High
palliative 50 62.80 Quite High
Disease Link Frequency Relevance Heat
Cancer 2525 99.84 Very High Very High Very High
Rheumatoid Arthritis 182 99.84 Very High Very High Very High
Metastasis 473 99.72 Very High Very High Very High
Breast Cancer 2128 99.52 Very High Very High Very High
Apoptosis 546 99.40 Very High Very High Very High
Cardiovascular Disorder Under Development 96 99.36 Very High Very High Very High
Advanced Or Metastatic Breast Cancer 1092 99.24 Very High Very High Very High
Triple Negative Breast Cancer 18 98.68 Very High Very High Very High
Recurrence 276 98.64 Very High Very High Very High
Carcinoma 32 98.36 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
HKI-272 is an irreversible orally active pan-HER receptor tyrosine kinase inhibitor with potential anti-neoplastic activity.
Negative_regulation (inhibitor) of pan-HER receptor tyrosine kinase
1) Confidence 0.57 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2579406 Disease Relevance 0.87 Pain Relevance 0.09
Another phase 3 trial, which is enrolling more than 1,200 patients in this setting and has just finished recruitment, is investigating letrozole in combination with lapatinib, a dual inhibitor of HER2 and HER1 tyrosine kinases [84].
Negative_regulation (inhibitor) of HER2
2) Confidence 0.55 Published 2007 Journal Breast Cancer Res Treat Section Body Doc Link PMC2001217 Disease Relevance 0.68 Pain Relevance 0
Dual ErbB2 blockade has also been trialled in patients progressing on trastuzumab.
Negative_regulation (blockade) of ErbB2
3) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.26 Pain Relevance 0.04
Prolonged inhibition of ErbB2 kinase activity resulted in upregulation of the transcription factor FOXO3A which upregulates estrogen receptor (ER) expression and signaling.
Negative_regulation (inhibition) of ErbB2
4) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.43 Pain Relevance 0.11
This review focuses on lapatinib, the small molecule tyrosine kinase inhibitor of both EGFR and HER2.
Negative_regulation (inhibitor) of HER2
5) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.67 Pain Relevance 0
Dual blockade of HER2 and HR may overcome this crosstalk and improve outcomes.
Negative_regulation (blockade) of HER2
6) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.48 Pain Relevance 0
Role of lapatinib in the first-line treatment of patients with metastatic breast cancer

Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2).

Negative_regulation (inhibitor) of ErbB2 associated with advanced or metastatic breast cancer
7) Confidence 0.54 Published 2010 Journal Cancer management and research Section Title Doc Link PMC3004582 Disease Relevance 1.09 Pain Relevance 0.03
A reasonable option would be continued blockade of the HER2 receptor by lapatinib whilst changing the concurrent therapy, however no controlled clinical studies have been reported to currently support such an approach.
Negative_regulation (blockade) of HER2 receptor
8) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.95 Pain Relevance 0.04
In the endocrine treatment of HR-positive HER2-positive tumors, in which overexpression of HER2 may confer resistance to endocrine therapy, concurrent inhibition of HR and ErbB2 may enhance efficacy.
Negative_regulation (inhibition) of ErbB2 associated with cancer
9) Confidence 0.54 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.68 Pain Relevance 0
It is unclear, however, whether trastuzumab actually causes downregulation of Her2, as some studies have demonstrated that receptor levels remain basically unchanged on trastuzumab therapy (Lane et al 2001; Yakes et al 2002; Nahta et al 2002).
Spec (whether) Negative_regulation (downregulation) of Her2
10) Confidence 0.54 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721347 Disease Relevance 0.05 Pain Relevance 0
Also, blockade of HER-2
Negative_regulation (blockade) of HER-2
11) Confidence 0.49 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0.77 Pain Relevance 0
In a randomized comparative trial, letrozole and anastrozole significantly reduced proliferation in HR+, HER2+ or HER2?
Negative_regulation (reduced) of HER2
12) Confidence 0.48 Published 2007 Journal Breast Cancer Res Treat Section Body Doc Link PMC2001217 Disease Relevance 0.51 Pain Relevance 0
A very small pilot study showed that trastuzumab treatment caused HER2 downregulation and increased apoptosis in patients with dysplasia and adenocarcinoma arising in Barrett's esophagus [80].

2.5.

Negative_regulation (downregulation) of HER2 in esophagus associated with adenocarcinoma, cleidocranial dysplasia and apoptosis
13) Confidence 0.43 Published 2011 Journal Pathology Research International Section Body Doc Link PMC3005843 Disease Relevance 1.76 Pain Relevance 0
IHC grades 0 and 1 were defined as a negative result for HER2, and the lack of HER2 amplification was confirmed by FISH if HER2 was rated 2+ by IHC.
Negative_regulation (result) of HER2
14) Confidence 0.43 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2972282 Disease Relevance 0.21 Pain Relevance 0
Future directions of research in HER2-positive gastroesophageal cancer should focus on the evaluation of novel antibodies (such as pertuzumab, a dimerization inhibitor, and T-DM1, a drug that combines trastuzumab with a linked chemotherapy agent called maytansine), irreversible tyrosine kinase inhibitors (such as neratinib and BIBW 2992, both dual EGFR-HER2 inhibitors), and inhibitors of HER2-related downstream signaling (such as mammalian target of rapamycin (mTOR), heat shock protein 90 (Hsp90), and PI3K/Akt) and of receptor crosstalk (such as other HER family members, vascular endothelial growth factor receptor (VEGFR), and insulin-like growth factor receptor (IGFR)).
Negative_regulation (inhibitors) of HER2-related associated with cancer and shock
15) Confidence 0.43 Published 2011 Journal Pathology Research International Section Body Doc Link PMC3005843 Disease Relevance 0.63 Pain Relevance 0
"Triple negativity" was defined as a lack of expression of ER, PgR, and HER2.
Negative_regulation (lack) of HER2
16) Confidence 0.43 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2972282 Disease Relevance 0.21 Pain Relevance 0
Lapatinib in combination with capecitabine in the management of ErbB2-positive (HER2-positive) advanced breast cancer

Lapatinib is an oral, reversible, dual inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and human epidermal growth factor receptor type 2 ErbB2 (HER2).

Negative_regulation (inhibitor) of ErbB2 associated with advanced or metastatic breast cancer
17) Confidence 0.42 Published 2008 Journal Biologics : Targets & Therapy Section Title Doc Link PMC2727787 Disease Relevance 0.28 Pain Relevance 0
Lapatinib in combination with capecitabine in the management of ErbB2-positive (HER2-positive) advanced breast cancer

Lapatinib is an oral, reversible, dual inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and human epidermal growth factor receptor type 2 ErbB2 (HER2).

Negative_regulation (inhibitor) of HER2 associated with advanced or metastatic breast cancer
18) Confidence 0.42 Published 2008 Journal Biologics : Targets & Therapy Section Title Doc Link PMC2727787 Disease Relevance 0.28 Pain Relevance 0
Initial studies showed that this agent reduced ErbB2 levels and inhibited proliferation of trastuzumab resistant breast tumor cells.[17] This made it a potential agent in trastuzumab resistant HER2 positive patients.
Negative_regulation (reduced) of ErbB2 associated with breast cancer
19) Confidence 0.42 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2579406 Disease Relevance 1.27 Pain Relevance 0.07
Led by the success of trastuzumab's HER2 blocking capabilities in breast cancer, EGFR inhibition with an emphasis on HER2 inhibition continues to be an area of focus in the treatment of breast cancer patients.
Negative_regulation (inhibition) of HER2 associated with breast cancer
20) Confidence 0.42 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2579406 Disease Relevance 0.57 Pain Relevance 0

General Comments

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