INT199573

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.65
First Reported 2006
Last Reported 2009
Negated 4
Speculated 0
Reported most in Body
Documents 33
Total Number 33
Disease Relevance 20.79
Pain Relevance 0.75

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

mitochondrion (Abl1) DNA binding (Abl1) cytoplasm (Abl1)
cytosol (Abl1) nucleolus (Abl1) cell adhesion (Abl1)
Anatomy Link Frequency
CSF 2
plasma 1
bone marrow 1
hematopoietic cells 1
Abl1 (Mus musculus)
Abl1 - H396P (2) Abl1 - T315I (1)
Pain Link Frequency Relevance Heat
Central nervous system 69 97.60 Very High Very High Very High
Potency 72 95.44 Very High Very High Very High
cytokine 20 88.88 High High
Kinase C 1 83.44 Quite High
imagery 7 72.16 Quite High
nMDA receptor 31 68.36 Quite High
fibrosis 24 55.72 Quite High
ketamine 25 50.00 Quite Low
anesthesia 11 50.00 Quite Low
adenocard 1 49.08 Quite Low
Disease Link Frequency Relevance Heat
Cancer 165 99.98 Very High Very High Very High
Myeloproliferative Disorder 148 99.96 Very High Very High Very High
Myeloid Leukemia 1900 99.28 Very High Very High Very High
Genetic Translocation 9 99.28 Very High Very High Very High
Myelofibrosis 158 99.16 Very High Very High Very High
Myelodysplastic Syndromes 374 98.80 Very High Very High Very High
Reticulocytosis 10 98.42 Very High Very High Very High
Philadelphia Chromosome 77 98.04 Very High Very High Very High
Erythrocytosis 86 98.02 Very High Very High Very High
Recurrence 99 97.44 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
BCR-ABL mutants can be grouped based on imatinib sensitivity: sensitive (IC50 ?
Gene_expression (mutants) of ABL
1) Confidence 0.65 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2567340 Disease Relevance 0.40 Pain Relevance 0
The sensitivity of BCR-ABL mutants to dasatinib can be classified as sensitive (IC50 ?
Gene_expression (sensitivity) of ABL
2) Confidence 0.65 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2567340 Disease Relevance 0.41 Pain Relevance 0.05
AP-24534 and XL-228 have demonstrated activity in cell culture and in mice bearing xenograft tumors expressing T315I BCR-ABL mutants [55,56].
Gene_expression (expressing) of ABL associated with cancer
3) Confidence 0.58 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2567340 Disease Relevance 0.44 Pain Relevance 0.04
First, amplification of the bcr-abl gene and consequently the production of a higher amount of Bcr-Abl protein has been observed in cell line models selected for imatinib resistance (le Coutre et al 2000; Mahon et al 2000; Weisberg and Griffin 2001).
Gene_expression (production) of Abl
4) Confidence 0.55 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.28 Pain Relevance 0
In vitro experiments demonstrated that cells expressing the His396Pro variant of Bcr-Abl reverted to an imatinib sensitive state upon reduction of the Bcr-abl protein content with breakpoint specific siRNAs (Wohlbold et al 2003).



Gene_expression (expressing) of Abl (H396P)
5) Confidence 0.55 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.14 Pain Relevance 0
First, amplification of the bcr-abl gene and consequently the production of a higher amount of Bcr-Abl protein has been observed in cell line models selected for imatinib resistance (le Coutre et al 2000; Mahon et al 2000; Weisberg and Griffin 2001).
Gene_expression (production) of abl
6) Confidence 0.55 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.28 Pain Relevance 0
Decreasing the protein expression of a target kinase is also capable of restoring sensitivity to imatinib in cells overexpressing bcr-abl as well as in cells expressing a mutant bcr-abl variant conferring partially resistance to imatinib.
Gene_expression (expressing) of abl
7) Confidence 0.55 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.14 Pain Relevance 0
Decreasing the protein expression of a target kinase is also capable of restoring sensitivity to imatinib in cells overexpressing bcr-abl as well as in cells expressing a mutant bcr-abl variant conferring partially resistance to imatinib.
Gene_expression (overexpressing) of abl
8) Confidence 0.55 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.13 Pain Relevance 0
Dasatinib is well tolerated and has broad efficacy, resulting in durable responses in patients with any BCR-ABL mutation except for T3151 and mutations in codon 317 – most commonly F317L – including mutations that were highly resistant to imatinib, such as L248, Y253, E255, F359, and H396.
Gene_expression (mutation) of ABL
9) Confidence 0.53 Published 2009 Journal Therapeutics and Clinical Risk Management Section Abstract Doc Link PMC2697539 Disease Relevance 0.58 Pain Relevance 0
The gatekeeper mutation Thr315Ile mutation was the only resistant variant of Abl (Table 2) (Shah et al 2004).
Gene_expression (resistant) of Abl (T315I)
10) Confidence 0.48 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.18 Pain Relevance 0
In vitro experiments demonstrated that cells expressing the His396Pro variant of Bcr-Abl reverted to an imatinib sensitive state upon reduction of the Bcr-abl protein content with breakpoint specific siRNAs (Wohlbold et al 2003).



Gene_expression (expressing) of abl (H396P)
11) Confidence 0.48 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.20 Pain Relevance 0
Decreasing the protein expression of a target kinase is also capable of restoring sensitivity to imatinib in cells overexpressing bcr-abl as well as in cells expressing a mutant bcr-abl variant conferring partially resistance to imatinib.
Gene_expression (overexpressing) of abl
12) Confidence 0.48 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.14 Pain Relevance 0
First, amplification of the bcr-abl gene and consequently the production of a higher amount of Bcr-Abl protein has been observed in cell line models selected for imatinib resistance (le Coutre et al 2000; Mahon et al 2000; Weisberg and Griffin 2001).
Gene_expression (production) of Abl
13) Confidence 0.48 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.28 Pain Relevance 0
Dasatinib (BMS-354825, Sprycel®; Bristol Myers Squibb, New York, NY, USA) is a potent, second-generation, small-molecule, multitarget kinase inhibitor of BCR-ABL.
Gene_expression (generation) of ABL
14) Confidence 0.48 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697539 Disease Relevance 0.09 Pain Relevance 0
Other mechanisms of resistance to imatinib include alteration of the balance favoring the active state of ABL kinase, shifting the equilibrium between active and inactive states;15 a change in the conformation of the BCR-ABL protein, preventing imatinib from directly binding to its binding site;16 amplification of the BCR-ABL gene, leading to over-expression of BCR-ABL protein, as detected by FISH;13,16 or over-expression of the P-glycoprotein efflux pump, for which imatinib is the substrate.17,18 Additional mechanisms include the binding of the A1 acid glycoprotein (AGP) to imatinib in plasma, reducing its intracellular concentrations,19 or a less understood mechanism, the inhibition of ABCG2 protein functionality by imatinib.20
Gene_expression (expression) of ABL in plasma
15) Confidence 0.48 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697539 Disease Relevance 0.21 Pain Relevance 0
After its approval in Switzerland the manufacturer now is hoping to launch its second-generation Bcr-Abl inhibitor, nilotinib, in the very near future in other countries.
Gene_expression (generation) of Abl
16) Confidence 0.43 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.09 Pain Relevance 0.03
In complementary studies where diseased mice were treated with dasatinib, a potent inhibitor of both ABL and Src kinases, there was minimal response of polycythemia and reticulocytosis to a regimen that is very effective for treatment of mice inoculated with BCR-ABL-expressing cells [27].
Gene_expression (expressing) of ABL associated with reticulocytosis and erythrocytosis
17) Confidence 0.39 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.05 Pain Relevance 0
Interestingly, dasatinib-resistant Bcr-Abl kinase mutants (T315I and V299L) were detected in the CSF leukemic blasts of two patients who developed a CNS relapse on dasatinib, suggesting that the selection of a resistant clone, rather than poor CSF penetration, was the cause of relapse.44

Dasatinib in children and adolescents

Gene_expression (detected) of Bcr-Abl kinase in CSF associated with central nervous system and recurrence
18) Confidence 0.31 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 1.08 Pain Relevance 0.16
This translocation fuses the genes encoding BCR and ABL, resulting in expression of the constitutively active protein tyrosine kinase, BCR-ABL.
Gene_expression (expression) of ABL
19) Confidence 0.31 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 1.46 Pain Relevance 0
The chronic BCR-ABL negative myeloproliferative disorders (MPDs)
Neg (negative) Gene_expression (negative) of ABL associated with myeloproliferative disorder
20) Confidence 0.31 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721304 Disease Relevance 1.15 Pain Relevance 0

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox