INT114246

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Context Info
Confidence 0.49
First Reported 2003
Last Reported 2010
Negated 3
Speculated 1
Reported most in Body
Documents 13
Total Number 14
Disease Relevance 8.67
Pain Relevance 0.70

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

endosome (EGFR) cell morphogenesis (EGFR) Golgi apparatus (EGFR)
endoplasmic reticulum (EGFR) intracellular (EGFR) enzyme binding (EGFR)
Anatomy Link Frequency
face 2
lung 2
EGFR (Homo sapiens)
Pain Link Frequency Relevance Heat
Potency 5 100.00 Very High Very High Very High
Taxol 4 86.40 High High
cINOD 91 85.80 High High
Pain 6 84.48 Quite High
adenocard 3 83.80 Quite High
cva 3 77.60 Quite High
pruritus 8 54.72 Quite High
imagery 4 50.84 Quite High
Central nervous system 6 40.04 Quite Low
abdominal pain 6 34.48 Quite Low
Disease Link Frequency Relevance Heat
Osteogenic Sarcomas 79 99.84 Very High Very High Very High
Cancer 323 99.70 Very High Very High Very High
Non-small-cell Lung Cancer 24 99.16 Very High Very High Very High
Noninfiltrating Intraductal Carcinoma 12 99.08 Very High Very High Very High
Lung Cancer 57 99.02 Very High Very High Very High
Apoptosis 196 98.52 Very High Very High Very High
Thyroid Neoplasm 89 98.36 Very High Very High Very High
Metastasis 44 98.24 Very High Very High Very High
Colorectal Cancer 113 97.88 Very High Very High Very High
Osteoporosis 17 96.60 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Our data demonstrate that EGFR inhibition is not a consequence of caspase activation or due to the apoptotic effects of the drugs in that apoptosis was first detected 24 h after sulindac metabolite treatment, whereas downregulation of EGFR was seen as early as 1 to 12 hours after drug treatment.
Neg (not) Positive_regulation (consequence) of Negative_regulation (inhibition) of EGFR associated with apoptosis
1) Confidence 0.49 Published 2005 Journal J Carcinog Section Body Doc Link PMC1208922 Disease Relevance 0.33 Pain Relevance 0.24
Although this has changed the face of EGFR-inhibitor therapy in CRC, only 30% to 50% of patient have KRAS mutations, thus leaving a large proportion of patients that do not respond to EGFR inhibitors despite having WT KRAS.
Neg (not) Positive_regulation (respond) of Negative_regulation (inhibitors) of EGFR in face associated with colorectal cancer
2) Confidence 0.49 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.79 Pain Relevance 0
PTEN (the lipid phosphatase and tensin homolog) is a key tumor suppressor that normally regulates the activation of PI3K.66 The loss of PTEN and mutations in PI3K have been proposed to predict resistance to EGFR inhibitors, however, this is preliminary and no definite conclusions can be derived.64

Conclusions

Positive_regulation (resistance) of Negative_regulation (inhibitors) of EGFR associated with cancer
3) Confidence 0.49 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.59 Pain Relevance 0
A potential pharmacodynamic interaction induced by EGFR inhibition may have also led to a blunting of the therapeutic effects of bevacizumab and/or chemotherapy.34

Ongoing studies

Positive_regulation (induced) of Negative_regulation (inhibition) of EGFR
4) Confidence 0.49 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.73 Pain Relevance 0.07
such as CI-1033, a pan-ErbB tyrosine kinase inhibitor, should also be studied
Positive_regulation (studied) of Negative_regulation (inhibitor) of ErbB
5) Confidence 0.49 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0.20 Pain Relevance 0
One of the mutations (L858R) was previously identified in non-small cell lung cancer (NSCLC) patients and this mutation was found to increase sensitivity to EGFR inhibitor, Erlotinib.
Positive_regulation (increase) of Negative_regulation (inhibitor) of EGFR in lung associated with lung cancer and non-small-cell lung cancer
6) Confidence 0.47 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2970593 Disease Relevance 0.64 Pain Relevance 0.03
binding, as well as by inducing overall downregulation of EGFR through
Positive_regulation (inducing) of Negative_regulation (downregulation) of EGFR
7) Confidence 0.46 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0 Pain Relevance 0
Thus, we hypothesize that EGFR downregulation by sulindac metabolites is not due to activation of caspases, but rather is a result of increased proteasomal and/or lysosomal degradation.
Neg (not) Positive_regulation (due) of Negative_regulation (downregulation) of EGFR
8) Confidence 0.46 Published 2005 Journal J Carcinog Section Body Doc Link PMC1208922 Disease Relevance 0.27 Pain Relevance 0.10
Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h.
Positive_regulation (induced) of Negative_regulation (downregulation) of pEGFR
9) Confidence 0.40 Published 2005 Journal J Carcinog Section Abstract Doc Link PMC1208922 Disease Relevance 0.38 Pain Relevance 0.06
Preclinical studies conducted in human ductal carcinoma in situ (DCIS) xenografts in nude mice suggest a potential role for EGFR inhibitors.
Positive_regulation (role) of Negative_regulation (inhibitors) of EGFR associated with noninfiltrating intraductal carcinoma
10) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575526 Disease Relevance 0.87 Pain Relevance 0
The study concludes that "together, these data suggest that combined treatment with distinct EGFR inhibitory agents can augment the potency of EGFR signaling inhibition.
Positive_regulation (augment) of Negative_regulation (inhibition) of EGFR associated with potency
11) Confidence 0.33 Published 2005 Journal BMC Clin Pharmacol Section Body Doc Link PMC1090568 Disease Relevance 0.21 Pain Relevance 0.05
Using in vitro studies, it was shown that blockade of the epidermal growth factor receptor was effective in decreasing proliferation and receptor autophosphorylation of a human bone-derived renal cell carcinoma cell line.
Positive_regulation (effective) of Negative_regulation (blockade) of epidermal growth factor receptor associated with renal cancer
12) Confidence 0.26 Published 2003 Journal Clin. Orthop. Relat. Res. Section Abstract Doc Link 14600596 Disease Relevance 1.21 Pain Relevance 0.16
These data, taken together with studies demonstrating that gefitinib and erlotinib, well known EGFR inhibitors, have resulted in objective tumor responses in patients with EGFR-overexpressing tumors, suggest that EGFR inhibitors might be beneficial for therapy of refractory or metastatic MTC.
Spec (might) Positive_regulation (beneficial) of Negative_regulation (inhibitors) of EGFR associated with thyroid neoplasm and cancer
13) Confidence 0.20 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.97 Pain Relevance 0
The stimulation of estrogen receptors leads to the downregulation of EGFR in OS, resulting in cell cycle inhibition and apoptosis.
Positive_regulation (leads) of Negative_regulation (downregulation) of EGFR associated with apoptosis and osteogenic sarcomas
14) Confidence 0.16 Published 2010 Journal PPAR Research Section Body Doc Link PMC2825651 Disease Relevance 1.49 Pain Relevance 0

General Comments

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