INT123877

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Context Info
Confidence 0.57
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 40
Total Number 40
Disease Relevance 27.94
Pain Relevance 1.17

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

cytosol (ABL1) protein modification process (ABL1) mitochondrion (ABL1)
nucleolus (ABL1) nucleus (ABL1) DNA binding (ABL1)
Anatomy Link Frequency
platelet 7
bone marrow 2
immune system 1
intestine 1
ABL1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Bioavailability 2 100.00 Very High Very High Very High
Pain 59 99.40 Very High Very High Very High
Potency 17 94.12 High High
adenocard 2 90.48 High High
dexamethasone 7 85.40 High High
imagery 12 84.08 Quite High
Kinase C 6 81.16 Quite High
agonist 45 80.64 Quite High
cytokine 20 72.04 Quite High
headache 62 69.64 Quite High
Disease Link Frequency Relevance Heat
Leukemia 115 100.00 Very High Very High Very High
Disorders Of Creatine Metabolism 7 100.00 Very High Very High Very High
Chronic Myeloid Leukemia 48 99.84 Very High Very High Very High
Arthralgia 39 99.64 Very High Very High Very High
Myeloid Leukemia 506 99.54 Very High Very High Very High
Apoptosis 213 99.40 Very High Very High Very High
Non-small-cell Lung Cancer 8 99.06 Very High Very High Very High
Acute Renal Failure 83 99.02 Very High Very High Very High
Solid Tumor 49 99.00 Very High Very High Very High
Philadelphia Chromosome 18 98.52 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Imatinib is a relatively specific inhibitor of the BCR/ABL tyrosine kinase, effective in chronic myeloid leukemia (CML).
Negative_regulation (inhibitor) of BCR/ABL associated with leukemia and myeloid leukemia
1) Confidence 0.57 Published 2008 Journal Leuk. Lymphoma Section Abstract Doc Link 19052981 Disease Relevance 0.62 Pain Relevance 0
Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R).
Negative_regulation (inhibitor) of ABL in platelet
2) Confidence 0.52 Published 2003 Journal J. Exp. Clin. Cancer Res. Section Abstract Doc Link 16767900 Disease Relevance 0.70 Pain Relevance 0
Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R).
Negative_regulation (inhibitor) of ABL in platelet
3) Confidence 0.52 Published 2003 Journal J. Exp. Clin. Cancer Res. Section Abstract Doc Link 16767900 Disease Relevance 0.70 Pain Relevance 0
Nilotinib (Tasigna; Novartis Pharmaceuticals) is a second-generation BCR-ABL tyrosine kinase inhibitor newly approved for the treatment of imatinib-resistant or imatinib-intolerant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase or accelerated phase.
Negative_regulation (inhibitor) of ABL associated with leukemia and philadelphia chromosome
4) Confidence 0.42 Published 2010 Journal J Clin Pharmacol Section Abstract Doc Link 19948946 Disease Relevance 0.19 Pain Relevance 0
[Minor bcr/abl positive acute lymphoblastic leukemia preceded by knee joint pain due to bone marrow necrosis].
Negative_regulation (preceded) of bcr/abl in bone marrow associated with pain, necrosis, arthralgia and leukemia
5) Confidence 0.41 Published 2004 Journal Rinsho Ketsueki Section Title Doc Link 15609688 Disease Relevance 0.93 Pain Relevance 0.38
Imatinib[11-16], is a potent first generation selective inhibitor of tyrosine kinase activity of BCR-ABL1.
Negative_regulation (inhibitor) of BCR-ABL1
6) Confidence 0.39 Published 2010 Journal BMC Blood Disord Section Body Doc Link PMC3017013 Disease Relevance 0.82 Pain Relevance 0
Several potent inhibitors of imatinib-resistant BCR-ABL1 have been identified and approved for clinical use[28-32].
Negative_regulation (inhibitors) of BCR-ABL1
7) Confidence 0.39 Published 2010 Journal BMC Blood Disord Section Body Doc Link PMC3017013 Disease Relevance 0.20 Pain Relevance 0.05
Dasatinib was approved in 2006 for the treatment of imatinib-resistant chronic myelogenous leukemia and functions primarily through the inhibition of BCR-ABL and Src kinase.
Negative_regulation (inhibition) of BCR-ABL associated with chronic myeloid leukemia
8) Confidence 0.39 Published 2009 Journal Drug Metab. Dispos. Section Abstract Doc Link 19282395 Disease Relevance 0.10 Pain Relevance 0.09
Such enhanced cell death induced by the respective drug combinations was apparent even in NSCLC or CML cells exhibiting resistance to EGFR or Abl tyrosine kinase inhibitors, respectively.
Negative_regulation (inhibitors) of Abl associated with myeloid leukemia, non-small-cell lung cancer and death
9) Confidence 0.33 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20026060 Disease Relevance 1.25 Pain Relevance 0
In most of the studies performed the primary mechanism by which HDACi appeared to induce apoptosis in CML cells was through the reduction of BCR-ABL levels and therefore downregulation of the multiple signalling pathways controlling survival of the neoplastic cells.
Negative_regulation (reduction) of BCR-ABL associated with myeloid leukemia and apoptosis
10) Confidence 0.31 Published 2010 Journal Invest New Drugs Section Body Doc Link PMC3003795 Disease Relevance 0.55 Pain Relevance 0
Reduction of BCR-ABL levels post-HDACi treatment, observed in most cases of HDACi treated CML cells, appears to be a consequence of disrupted Hsp90 chaperone function and proteosomal degradation of BCR-ABL [12, 65, 67, 76].
Negative_regulation (Reduction) of BCR-ABL associated with myeloid leukemia
11) Confidence 0.31 Published 2010 Journal Invest New Drugs Section Body Doc Link PMC3003795 Disease Relevance 0.45 Pain Relevance 0
This reflects the fact that despite impaired absorption and transport from the intestine, subsequent transport of vitamin A in plasma by retinol-binding protein is not impaired in ABL.
Negative_regulation (impaired) of ABL in intestine
12) Confidence 0.30 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.57 Pain Relevance 0
During the ARF period, Pto/Cro negatively correlated both with decreased BCrC and BUC (Figure 2A,B) and positively correlated both with FeNa and FeK (Figure 2C,D).
Negative_regulation (decreased) of BCrC associated with acute renal failure and disorders of creatine metabolism
13) Confidence 0.23 Published 2008 Journal Crit Care Section Body Doc Link PMC2447585 Disease Relevance 1.59 Pain Relevance 0.03
In most of the studies performed the primary mechanism by which HDACi appeared to induce apoptosis in CML cells was through the reduction of BCR-ABL levels and therefore downregulation of the multiple signalling pathways controlling survival of the neoplastic cells.
Negative_regulation (downregulation) of BCR-ABL associated with myeloid leukemia and apoptosis
14) Confidence 0.23 Published 2010 Journal Invest New Drugs Section Body Doc Link PMC3003795 Disease Relevance 0.55 Pain Relevance 0
Imatinib mesylate (IM) (Gleevec®, Novartis), a 2-phenylaminopyrimidine derivative, is a potent inhibitor of targeted protein tyrosine kinases, including BCR-ABL, c-kit, and platelet-derived growth factor receptor (PDGF-R), and was developed in the mid-1990s against a background of some uncertainty.1–3 The drug appears to work principally by occupying the ATP binding site of the BCR-ABL oncoprotein and thereby preventing phosphorylation of the substrate and interrupting contact with the effector protein.
Negative_regulation (inhibitor) of ABL in platelet
15) Confidence 0.18 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.21 Pain Relevance 0
In preclinical data, mice were noted to have numerous teratogenic effects including perinatal mortality; abnormal spleen, head, and eye development; and abnormal immune system function.30 This has been speculated to be possibly related to the loss of Abl for a proper embryonic development.
Negative_regulation (loss) of Abl in immune system
16) Confidence 0.18 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.32 Pain Relevance 0
Principal long-term adverse effects of imatinib in patients with chronic myeloid leukemia in chronic phase

Imatinib mesylate (IM), an original Abl tyrosine kinase inhibitor, entered the clinics in 1998 for the treatment of patients with chronic myeloid leukemia (CML).

Negative_regulation (inhibitor) of Abl associated with leukemia and myeloid leukemia
17) Confidence 0.18 Published 2010 Journal Biologics : Targets & Therapy Section Title Doc Link PMC3010822 Disease Relevance 0.64 Pain Relevance 0
The introduction of imatinib, a tyrosine kinase inhibitor mainly targeting BCR-ABL, c-KIT and PDGFR, has profoundly improved the prognosis of both entities, while being surprisingly well tolerated.
Negative_regulation (inhibitor) of BCR-ABL
18) Confidence 0.11 Published 2009 Journal Drug Saf Section Abstract Doc Link 19810774 Disease Relevance 1.17 Pain Relevance 0.06
Dasatinib is a potent inhibitor of multiple oncogenic kinases including Src, cKIT, BCR-ABL, PDGFR, and ephrin A.
Negative_regulation (inhibitor) of BCR-ABL
19) Confidence 0.11 Published 2010 Journal Head Neck Oncol Section Body Doc Link PMC2868849 Disease Relevance 0.65 Pain Relevance 0
Imatinib (Gleevec) inhibits the continuously active tyrosine kinase, Bcr-Abl, which results from the translocation of chromosomes 9 and 22 and is effective for the treatment of CML as well as ALL; however, cardiotoxicity is a potentially serious side effect of this drug as well [340].
Negative_regulation (inhibits) of Bcr-Abl associated with myeloid leukemia and cardiovascular disorder under development
20) Confidence 0.08 Published 2010 Journal PPAR Research Section Body Doc Link PMC2829627 Disease Relevance 1.08 Pain Relevance 0.08

General Comments

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