INT109396

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Context Info
Confidence 0.42
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 12
Total Number 12
Disease Relevance 14.92
Pain Relevance 1.06

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

endosome (RET) signal transduction (RET) plasma membrane (RET)
Anatomy Link Frequency
thyroid 5
neurons 1
ganglion cell 1
RET (Homo sapiens)
Pain Link Frequency Relevance Heat
Hsan 1 99.82 Very High Very High Very High
dorsal root ganglion 6 99.68 Very High Very High Very High
Spinal cord 2 94.80 High High
Dorsal horn 3 90.32 High High
intrathecal 1 86.88 High High
Neuropathic pain 2 75.00 Quite High
substance P 1 74.88 Quite High
spinal dorsal horn 1 72.16 Quite High
Peripheral nerve injury 2 66.56 Quite High
Potency 1 61.28 Quite High
Disease Link Frequency Relevance Heat
Thyroid Neoplasm 880 100.00 Very High Very High Very High
Multiple Endocrine Neoplasia Type 2a 131 100.00 Very High Very High Very High
Recurrence 56 100.00 Very High Very High Very High
Multiple Endocrine Neoplasia Type 2b 51 100.00 Very High Very High Very High
Hereditary Sensory And Autonomic Neuropathies 1 99.82 Very High Very High Very High
Ganglion Cysts 10 99.68 Very High Very High Very High
Disease 179 98.62 Very High Very High Very High
Cancer 338 95.76 Very High Very High Very High
Apoptosis 18 95.48 Very High Very High Very High
Hyperplasia 8 94.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Similarly, the orally administered multitarget tyrosine kinase inhibitor, sunitinib, has been shown to be a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases [21].
Negative_regulation (inhibitor) of RET in thyroid associated with thyroid neoplasm
1) Confidence 0.42 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.81 Pain Relevance 0
In fact, receptor rearrangements or point mutations convert RET and NTRK1 in dominantly acting transforming genes leading to thyroid tumors, whereas inactivating mutations, associated with Hirschsprung's disease (HSCR) and congenital insensitivity to pain with anhidrosis (CIPA), impair RET and NTRK1 functions, respectively.
Negative_regulation (impair) of RET in thyroid associated with thyroid neoplasm, disease and hsan
2) Confidence 0.41 Published 2003 Journal J. Cell. Physiol. Section Abstract Doc Link 12652644 Disease Relevance 0.68 Pain Relevance 0.10
AMG-706 Finally, in a third abstract reported at the 2007 annual meeting of the American Society of Clinical Oncology, AMG-706, another multikinase inhibitor (VEGF/PDGF receptors, Kit and RET), was studied in a phase II trial of patients with advanced differentiated thyroid cancer or medullary thyroid cancer.
Negative_regulation (inhibitor) of RET in thyroid associated with thyroid neoplasm
3) Confidence 0.40 Published 2010 Journal Journal of Thyroid Research Section Body Doc Link PMC2956973 Disease Relevance 1.16 Pain Relevance 0
Inhibitors of the activated RET proto-oncogene and other RTK inhibitors appear particularly promising, based on the high prevalence of mutated oncogenes and specific expression patterns in MTC [2].
Negative_regulation (Inhibitors) of RET associated with thyroid neoplasm
4) Confidence 0.35 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.79 Pain Relevance 0
MTC usually occurs in a decreasing order of severity in MEN2B, MEN2A and FMTC, respectively [6].
Negative_regulation (decreasing) of MEN2B associated with multiple endocrine neoplasia type 2a, thyroid neoplasm and multiple endocrine neoplasia type 2b
5) Confidence 0.34 Published 2006 Journal Orphanet J Rare Dis Section Body Doc Link PMC1654141 Disease Relevance 3.29 Pain Relevance 0.06
MTC usually occurs in a decreasing order of severity in MEN2B, MEN2A and FMTC, respectively [6].
Negative_regulation (decreasing) of MEN2A associated with multiple endocrine neoplasia type 2a, thyroid neoplasm and multiple endocrine neoplasia type 2b
6) Confidence 0.34 Published 2006 Journal Orphanet J Rare Dis Section Body Doc Link PMC1654141 Disease Relevance 3.29 Pain Relevance 0.06
Many of these agents which are earlier in the development pipeline are capable of inhibiting RET at subnanomolar concentrations and hold significant promise for the treatment and palliation of hereditary MTC [2].

3.2.

Negative_regulation (inhibiting) of RET associated with thyroid neoplasm
7) Confidence 0.31 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.96 Pain Relevance 0
Similarly, the orally administered multitarget tyrosine kinase inhibitor, SU11248 (sunitinib), has been shown to be a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases (Kim et al 2006).


Negative_regulation (inhibitor) of RET in thyroid associated with thyroid neoplasm
8) Confidence 0.30 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621417 Disease Relevance 1.20 Pain Relevance 0
Furthermore, TSH suppression by administration of thyroid hormone (L-thyroxine) has been shown to lower the recurrence rates FTC and PTC (Emerick et al 1993; Young et al 1980; Clark 1981; Mazzaferri 1987; Mazzaferri and Jhiang 1994) and improves survival after thyroidectomy (Schneider et al 1978; Fogelfeld et al 1998).
Negative_regulation (lower) of PTC in thyroid associated with thyroid neoplasm and recurrence
9) Confidence 0.14 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621417 Disease Relevance 1.04 Pain Relevance 0.03
Vandetanib (ZD-6474) is a TK inhibitor of VEGFRR-2, VEGFR-3, Ret and EGFR (Ciardiello et al 2003) thus inhibiting both the VEGF dependent angiogenesis and EGFR dependent tumor cell proliferation.
Negative_regulation (inhibitor) of Ret associated with cancer
10) Confidence 0.09 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727890 Disease Relevance 0.42 Pain Relevance 0.03
Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in cleaved caspase-3, Bcl-2, and cleaved PARP proteins that are associated with apoptosis and no change in the ganglion cell specific marker, neurofilament (NF-L).
Negative_regulation (decrease) of RET-P1 in ganglion cell associated with ganglion cysts and apoptosis
11) Confidence 0.04 Published 2007 Journal Brain Res. Bull. Section Abstract Doc Link 17562394 Disease Relevance 0.26 Pain Relevance 0
Of the intensely galectin-1-IR DRG neurons, 93.9% displayed c-Ret mRNA positive signals.
Negative_regulation (displayed) of c-Ret mRNA in neurons associated with dorsal root ganglion
12) Confidence 0.03 Published 2003 Journal Brain Res. Section Abstract Doc Link 14642832 Disease Relevance 0.89 Pain Relevance 0.78

General Comments

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