INT205401

Context Info Confidence 0.51 First Reported 2007 Last Reported 2010 Negated 3 Speculated 0 Reported most in Body Documents 32 Total Number 32 Disease Relevance 13.99 Pain Relevance 0.77

kinase activity (Chkb) cytoplasm (Chkb)

Anatomy Link Frequency plasma 2 muscle 2 blood 1 neuron 1 hind limb 1 Chkb (Mus musculus)

Pain Link Frequency Relevance Heat ischemia 75 98.72 fibrosis 136 86.16 Inflammation 68 85.28 metalloproteinase 21 80.20 imagery 31 77.08 chemokine 5 75.28 cytokine 45 74.84 Inflammatory response 18 65.32 agonist 10 62.24 Angina 7 29.84

Disease Link Frequency Relevance Heat Cancer 622 99.84 Breast Cancer 236 99.18 Injury 195 98.76 Apoptosis 209 98.72 Cv Unclassified Under Development 72 98.72 Fatigue 2 98.12 Muscle Weakness 9 97.94 Myocardial Infarction 179 97.92 Death 83 97.64 Disease 95 97.16

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Anatomy

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Disease term

The differential expression of CK and EpCAM on the same cell will be the key to ensure that no target cells are missed.

Gene_expression (expression) of CK

1) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.50 Pain Relevance 0

Those tumor cells that express CK but with low or no EpCAM, or vice versa [15-19], may not be enriched by anti-EpCAM antibody.

Gene_expression (express) of CK associated with cancer

2) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.55 Pain Relevance 0

Our method detected CTCs in blood samples from the same or different breast cancer patients with various sizes, shapes and CK expression levels (Figure 3(a)).

Gene_expression (expression) of CK in blood associated with breast cancer

3) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.29 Pain Relevance 0.04

They also showed that the anti-EpCAM antibody may compensate for low CK expression, giving a better sensitivity and reproducibility for CTC detection in the new strategy (Figure 4(d)).

Gene_expression (expression) of CK

4) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.12 Pain Relevance 0

These variations may be a result of the low frequency of CTCs or the heterogeneity of CK and EpCAM expression in the CTCs, resulting in certain types of CTCs being missed by one or the another enrichment methods.

Gene_expression (expression) of CK

5) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.15 Pain Relevance 0

In the case of CTCs that express low or no EpCAM and low or no CK, we need different strategies to enrich and target the correct cells.

Neg (no) Gene_expression (express) of CK

6) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.47 Pain Relevance 0

Since most of the CTCs express both CK and EpCAM [51], this new CTC-enrichment strategy will consistently enrich most CTCs with CK+&EpCAM+, CK-/low&EpCAM+ or CK+&EpCAM-/low.

Gene_expression (express) of CK

7) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.06 Pain Relevance 0

Because CK and EpCAM are both heterogeneously expressed on tumor cells (Figures 3 and 4(d)) [15,19,48], the enrichment with the combined antibodies may increase the sensitivity and reproducibility by the compensation effect of biomarkers from each other.

Gene_expression (expressed) of CK associated with cancer

8) Confidence 0.51 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.18 Pain Relevance 0

Our data regarding prednisone are consistent with the reports beneficial effects on serum CK levels in mdx mice [16].

Gene_expression (levels) of CK

9) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2888587 Disease Relevance 0 Pain Relevance 0

To compensate for low or no expression of EpCAM and CK, we also developed an assay with a combination of anti-CK and anti-EpCAM antibodies that allows the enrichment of all types of CTCs including CK+&EpCAM+, CK+&EpCAM-/low and CK-/low&EpCAM+ tumor cells.

Neg (no) Gene_expression (expression) of CK associated with cancer

10) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.54 Pain Relevance 0

The CellSearch™ system represents an example of CTC enrichment with anti-EpCAM and detection with CK.

Gene_expression (detection) of CK

11) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.17 Pain Relevance 0

Only the cells with CK and DAPI positive, and CD45 negative [10-15,20] were counted as CTCs.

Neg (negative) Gene_expression (negative) of CK

12) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.12 Pain Relevance 0

By comparing the average CK intensity of the enriched CTCs, the enrichment with the combination antibodies (anti-CK and anti-EpCAM) showed not only a higher CTC count, but also detected more CTCs with relatively low CK expression levels (Figure 4(d)).

Gene_expression (expression) of CK

13) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.21 Pain Relevance 0

In the case of direct labeling, we used a set of fluorescein isothiocyanate (FITC) conjugated anti-mouse IgG1 antibodies recognising CK 8, 18 and 19 (CTC Enrichment and Detection Kit, Genetix, New Milton, UK); haematopoietic cells were stained with a DyeLight 549 conjugated anti-mouse IgG1 antibody recognising CD45 (CTC Enrichment and Detection Kit, Genetix, New Milton, UK).

Gene_expression (recognising) of CK in haematopoietic cells

14) Confidence 0.38 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575542 Disease Relevance 0.20 Pain Relevance 0

Even though the prednisone- and combination-treated groups showed a trend toward a decrease in serum CK levels, these changes were not statistically significant.

Gene_expression (levels) of CK

15) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2888587 Disease Relevance 0 Pain Relevance 0

As shown in Figure 2A, the CK level was significantly less in the rhBCL2A1-pretreated mice compared with the rhBim-pretreated mice.

Gene_expression (level) of CK

16) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2816997 Disease Relevance 0.66 Pain Relevance 0.05

Hind limb ischemia was induced by aorta cross clamping for 90 minutes, and plasma CK levels were measured 3 hours after reperfusion.

Gene_expression (levels) of CK in plasma associated with ischemia

17) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2816997 Disease Relevance 0.67 Pain Relevance 0.05

Plasma CK levels in rats pretreated with rhBCL2A1 the day prior to tourniquet I/R of hind limb were significantly less than CK levels in rats pretreated with rhBim (Figure 2B).

Gene_expression (levels) of CK in hind limb

18) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2816997 Disease Relevance 1.00 Pain Relevance 0.04

On the other hand, we did not observe significant changes in muscle histology; behavioral measurements, heart function or serum CK levels after arginine butyrate treatment.

Gene_expression (levels) of CK in heart

19) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2888587 Disease Relevance 0.57 Pain Relevance 0.11

We did not see any significant differences in behavioral activity, Rotarod performance, histology, or serum CK levels between the drug-treated groups and the saline-treated control group.

Gene_expression (levels) of CK

20) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2888587 Disease Relevance 0.76 Pain Relevance 0.16

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