INT228128

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Context Info
Confidence 0.67
First Reported 2008
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 31
Total Number 31
Disease Relevance 18.31
Pain Relevance 1.25

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

cytosol (Bcl2l11) mitochondrion (Bcl2l11) cytoplasm (Bcl2l11)
Anatomy Link Frequency
leukocytes 1
T cells 1
Bcl2l11 (Mus musculus)
Pain Link Frequency Relevance Heat
ischemia 74 97.12 Very High Very High Very High
chemokine 422 96.56 Very High Very High Very High
Arthritis 64 83.16 Quite High
Inflammation 61 82.76 Quite High
cytokine 68 76.72 Quite High
imagery 84 65.24 Quite High
antagonist 4 38.16 Quite Low
rheumatoid arthritis 65 30.92 Quite Low
anesthesia 36 5.00 Very Low Very Low Very Low
isoflurane 16 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Apoptosis 1281 100.00 Very High Very High Very High
Repression 101 100.00 Very High Very High Very High
Adhesions 718 99.62 Very High Very High Very High
Disease 55 98.72 Very High Very High Very High
Colon Cancer 500 98.70 Very High Very High Very High
Metastasis 501 98.60 Very High Very High Very High
Cancer 434 98.40 Very High Very High Very High
Cv Unclassified Under Development 74 97.12 Very High Very High Very High
Autoimmune Disease 23 96.32 Very High Very High Very High
Death 275 95.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The mitochondrial pathway has been implicated in immune response shutdown, because Bcl-2 overexpression (Strasser et al., 1991), loss of Bim (Hildeman et al., 2002; Pellegrini et al., 2003), or Bax and Bak deficiency (Rathmell et al., 2002) inhibited death of T cells stimulated in vitro or in vivo by a single dose of SEB or in vivo after infection with human herpes simplex virus (HSV-1).
Gene_expression (overexpression) of Bim in T cells associated with cold sores, herpes simplex virus, infection and death
1) Confidence 0.67 Published 2008 Journal Immunity Section Body Doc Link PMC2270348 Disease Relevance 0.84 Pain Relevance 0.06
For example, abnormally increased levels of Bim and enhanced sensitivity to FasL (Gougeon, 2003) have been detected in leukocytes from patients infected with human immunodeficiency virus (HIV) or other pathogens.
Gene_expression (levels) of Bim in leukocytes associated with acquired immune deficiency syndrome or hiv infection
2) Confidence 0.67 Published 2008 Journal Immunity Section Body Doc Link PMC2270348 Disease Relevance 0.54 Pain Relevance 0.03
Faslpr/lpr and Bcl2l11+/?
Gene_expression (/) of Bcl2l11
3) Confidence 0.58 Published 2008 Journal Immunity Section Body Doc Link PMC2270348 Disease Relevance 0.52 Pain Relevance 0.04
In cells isolated from matrigel, HF diet down-regulated expression of pro-apoptotic Bcl-2 family members: Bak1, Bad, and Bcl2L11.
Gene_expression (expression) of Bcl2L11 associated with apoptosis
4) Confidence 0.57 Published 2009 Journal Lipids Health Dis Section Body Doc Link PMC2674043 Disease Relevance 0.49 Pain Relevance 0
Coinciding with our data, decreased Bak and Bim expression are correlated with diminished disease prognosis suggesting downregulation of these proteins are critical for apoptotic resistance [31], [32].
Gene_expression (expression) of Bim associated with apoptosis and disease
5) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.97 Pain Relevance 0.05
HCT116 GFP and CXCL12 stable cell lines (1×105) expressing Bim or scramble shRNAs were plated to 12-well dishes on a 1.0 ml layer of 0.7% (w/v) bacto-agar (BD Bioscience) reconstituted in serum-containing medium.
Gene_expression (expressing) of Bim
6) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0 Pain Relevance 0
Bim protein expression was markedly increased in three separate clones of CXCL12 expressing cells, consistent with its key role in anoikis-sensitivity and decreased metastatic potential in those cells (Figure 4E).
Gene_expression (expression) of Bim
7) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.35 Pain Relevance 0.05
Moreover, our analyses indicate focal adhesion protein loss of activity and degradation temporally precedes alterations in Mcl-1 and Bim expression levels, which themselves regulate activation of the caspase family members (Figure 9).
Gene_expression (expression) of Bim associated with adhesions
8) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 1.30 Pain Relevance 0.03
Having demonstrated Bim expression was upregulated in non-adherent colorectal carcinoma cells expressing CXCL12, we next examined whether RNAi-mediated repression of Bim would reverse anoikis sensitivity in those cells.
Gene_expression (expression) of Bim associated with repression and colon cancer
9) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.52 Pain Relevance 0
Previous studies suggest degradation of Mcl-1 modulates expression of Bim to repress anoikis [9].
Gene_expression (expression) of Bim
10) Confidence 0.28 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 1.02 Pain Relevance 0
Consistent with its key role in anoikis, Bim was undetectable in these adherent culture time points (data not shown), further supporting the notion that loss of focal adhesions and decreased adherence precede Bim upregulation.
Gene_expression (undetectable) of Bim associated with adhesions
11) Confidence 0.25 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.30 Pain Relevance 0.04
We hypothesize that maintaining focal adhesion protein expression, which is absent in CXCL12 cells regardless of Bim levels, is critical for further enabling metastasis of colorectal carcinomas expressing the chemokine.
Neg (absent) Gene_expression (levels) of Bim associated with chemokine, colon cancer, metastasis and adhesions
12) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 1.31 Pain Relevance 0.17
Having demonstrated Bim expression was upregulated in non-adherent colorectal carcinoma cells expressing CXCL12, we next examined whether RNAi-mediated repression of Bim would reverse anoikis sensitivity in those cells.
Gene_expression (repression) of Bim associated with repression and colon cancer
13) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.51 Pain Relevance 0
Immunoblot (Figure 6A) and densitometry (Figure 6B) analyses of non-adherent cultures confirmed the 75% knockdown efficiency of Bim protein levels in CXCL12-expressing cells.
Gene_expression (levels) of Bim
14) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.46 Pain Relevance 0
Together, these data indicate that persistent CXCL12 stimulation induces anoikis by shifting the balance between Bim and Mcl-1/Bcl-2 levels to activate caspase-9 and intrinsic apoptosis.


Gene_expression (levels) of Bim associated with apoptosis
15) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.31 Pain Relevance 0.03
Further, our data indicate that Bim depletion had little effect on formation or stability of focal adhesion proteins, with FAK levels decreasing equally in Bim knockdown and Bim-competent CXCL12 cells.
Gene_expression (depletion) of Bim associated with adhesions
16) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 1.15 Pain Relevance 0
The sequences for Bim shRNA oligos were as follows: 5?
Gene_expression (oligos) of Bim
17) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0 Pain Relevance 0
Interestingly, Bim repression resulted in the concomitant increase in Mcl-1 and Bcl-2 levels in CXCL12-producing, but not wild-type, cells mirroring our results seen in HT29 cells (Figure 4D).
Gene_expression (repression) of Bim associated with repression
18) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.46 Pain Relevance 0
CXCL12 expression and adhesion are unaffected by Bim repression
Gene_expression (repression) of Bim associated with repression and adhesions
19) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2943927 Disease Relevance 0.51 Pain Relevance 0
Infarct volume (Vinfarct), expressed as a percentage of the VAAR, was significantly less in the rhBCL2A1-treated mice compared with rhBim-treated mice.


Gene_expression (less) of rhBim
20) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2816997 Disease Relevance 0.36 Pain Relevance 0.11

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