INT203253

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Context Info
Confidence 0.92
First Reported 2007
Last Reported 2007
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 24
Disease Relevance 20.16
Pain Relevance 0.43

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

cytosol (Xiap) nucleus (Xiap) intracellular (Xiap)
protein complex (Xiap) ligase activity (Xiap) cytoplasm (Xiap)
Anatomy Link Frequency
cleavage 4
bands 1
Xiap (Mus musculus)
Pain Link Frequency Relevance Heat
depression 24 81.60 Quite High
headache 24 79.44 Quite High
Disease Link Frequency Relevance Heat
Melanoma 1752 100.00 Very High Very High Very High
Apoptosis 504 99.80 Very High Very High Very High
Cancer 624 99.74 Very High Very High Very High
Ovarian Cancer 240 98.68 Very High Very High Very High
Aggression 24 93.52 High High
Disease 120 93.08 High High
Malignant Neoplastic Disease 240 92.12 High High
Targeted Disruption 48 91.64 High High
Nevus 528 90.76 High High
Toxicity 72 88.96 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Here we assessed whether pretreatment of melanoma cells with Phenoxodiol reverses the baseline resistance to Carboplatin and whether this reversal is associated with XIAP degradation.
Protein_catabolism (degradation) of XIAP associated with melanoma
1) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.34 Pain Relevance 0
Although the precise target of Phenoxodiol remains unknown, it inhibits XIAP by causing early, caspase independent self-ubiquitination and degradation of XIAP by the proteasome [19].
Protein_catabolism (degradation) of XIAP
2) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.78 Pain Relevance 0.09
We further hypothesize that drugs that (directly or indirectly) cause XIAP degradation can result in sensitization of melanoma cells to chemotherapy.
Protein_catabolism (degradation) of XIAP associated with melanoma
3) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 1.31 Pain Relevance 0.12
Furthermore, we demonstrate that Phenoxodiol sensitization to Carboplatin in melanoma is associated with XIAP degradation, although the precise target of Phenoxodiol is still being studied in our laboratory.
Protein_catabolism (degradation) of XIAP associated with melanoma
4) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.70 Pain Relevance 0
Furthermore, we demonstrate that degradation of XIAP by Phenoxodiol confers Carboplatin sensitization in melanoma cells.
Protein_catabolism (degradation) of XIAP associated with melanoma
5) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 1.16 Pain Relevance 0
Phenoxodiol is an isoflavone derivative that has been shown to cause proteasomal degradation of XIAP, and reverse chemoresistance in ovarian cancer cells [19].
Protein_catabolism (degradation) of XIAP associated with ovarian cancer
6) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.88 Pain Relevance 0
The precise target and mechanism of action of Phenoxodiol remain unknown, and XIAP degradation might be a downstream effect of Phenoxodiol, rather than a direct effect of the drug.
Protein_catabolism (degradation) of XIAP
7) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 1.01 Pain Relevance 0
In these studies we showed that when cells are transfected with a phospho-mimic form of XIAP, which is resistant to proteasomal degradation, Phenoxodiol activity is inhibited, indicating that XIAP degradation is a critical component of Phenoxodiol-induced apoptosis.
Protein_catabolism (degradation) of XIAP associated with apoptosis
8) Confidence 0.92 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.93 Pain Relevance 0.12
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization

XIAP up-regulation is associated with chemotherapy resistance.

Protein_catabolism (cleavage) of XIAP in cleavage associated with melanoma and apoptosis
9) Confidence 0.81 Published 2007 Journal J Transl Med Section Title Doc Link PMC1796544 Disease Relevance 1.00 Pain Relevance 0
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization

XIAP up-regulation is associated with chemotherapy resistance.

Protein_catabolism (cleavage) of XIAP in cleavage associated with melanoma and apoptosis
10) Confidence 0.81 Published 2007 Journal J Transl Med Section Title Doc Link PMC1796544 Disease Relevance 1.00 Pain Relevance 0
In these studies we showed that when cells are transfected with a phospho-mimic form of XIAP, which is resistant to proteasomal degradation, Phenoxodiol activity is inhibited, indicating that XIAP degradation is a critical component of Phenoxodiol-induced apoptosis.
Protein_catabolism (degradation) of XIAP associated with apoptosis
11) Confidence 0.81 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.91 Pain Relevance 0.11
These clinical trials should incorporate assessment of XIAP degradation in short term cultures after treatment with Phenoxodiol as a biomarker of response to this combination of therapy.
Protein_catabolism (degradation) of XIAP
12) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.62 Pain Relevance 0
In this study we demonstrated that Phenoxodiol treatment of melanoma cells also caused XIAP degradation, cleavage of pro-caspase-2, and activation of caspases -3, -8 and -9 in Carboplatin resistant melanoma cell lines.
Protein_catabolism (degradation) of XIAP in cleavage associated with melanoma
13) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 1.02 Pain Relevance 0
We note that in the YUSAC2 cells there was much less XIAP degradation and no meaningful sensitization to Carboplatin.
Protein_catabolism (degradation) of XIAP
14) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.59 Pain Relevance 0
Phenoxodiol causes XIAP degradation and chemotherapy sensitization in ovarian cancer.
Protein_catabolism (degradation) of XIAP associated with ovarian cancer
15) Confidence 0.80 Published 2007 Journal J Transl Med Section Abstract Doc Link PMC1796544 Disease Relevance 0.86 Pain Relevance 0
A central effect of Phenoxodiol-induced apoptosis in different cell types, is degradation of XIAP [17,19].
Protein_catabolism (degradation) of XIAP associated with apoptosis
16) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.81 Pain Relevance 0
Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization.
Protein_catabolism (degradation) of XIAP associated with apoptosis
17) Confidence 0.80 Published 2007 Journal J Transl Med Section Abstract Doc Link PMC1796544 Disease Relevance 1.34 Pain Relevance 0
However, in select patients whose tumors demonstrate XIAP degradation with Phenoxodiol treatment, use of Phenoxodiol as a chemotherapy sensitizer is a reasonable approach that warrants further investigation.
Protein_catabolism (degradation) of XIAP associated with cancer
18) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.51 Pain Relevance 0
On the other hand, with the YUSAC2 cells, the degree XIAP degradation and resultant caspase activation was much less than what was observed with YUMAC cells (Figure 6B).


Protein_catabolism (degradation) of XIAP
19) Confidence 0.80 Published 2007 Journal J Transl Med Section Body Doc Link PMC1796544 Disease Relevance 0.21 Pain Relevance 0
Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization.
Protein_catabolism (degradation) of XIAP associated with apoptosis
20) Confidence 0.80 Published 2007 Journal J Transl Med Section Abstract Doc Link PMC1796544 Disease Relevance 1.32 Pain Relevance 0

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