INT182313

Context Info Confidence 0.60 First Reported 2005 Last Reported 2010 Negated 6 Speculated 3 Reported most in Body Documents 18 Total Number 21 Disease Relevance 15.34 Pain Relevance 0.96

nuclear chromosome (Birc5) chromosome segregation (Birc5) intracellular (Birc5) enzyme binding (Birc5) embryo development (Birc5) cytoplasm (Birc5)

Anatomy Link Frequency biliary tract 2 colon 2 neurogenic regions 2 Birc5 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammatory response 3 99.84 cINOD 111 99.72 rheumatoid arthritis 77 94.72 COX-2 inhibitor 30 87.48 Hippocampus 26 65.76 long-term potentiation 6 58.52 Bile 12 50.00 Inflammation 11 31.12 methotrexate 17 11.04 gABA 2 5.56

Disease Link Frequency Relevance Heat INFLAMMATION 25 99.84 Pancreatic Cancer 200 99.52 Cancer 1019 99.42 Biliary Cancer 20 99.28 Death 121 99.12 Myocardial Infarction 69 98.68 Diabetes Mellitus 93 98.56 Apoptosis 626 98.16 Glioblastoma 120 97.32 Lymphatic System Cancer 41 96.76

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

When two different tumor cell lines were treated with various concentrations of the above inhibitors, no effect on survivin expression was observed, even at concentrations of up to 100 ?

Neg (no) Regulation (effect) of Gene_expression (expression) of survivin associated with cancer

1) Confidence 0.60 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.15 Pain Relevance 0.16

Finally, we investigated whether the effects of DMC and celecoxib on survivin expression would also take place in vivo.

Spec (whether) Regulation (effects) of Gene_expression (expression) of survivin

2) Confidence 0.60 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 1.01 Pain Relevance 0

Thus, the differential effects of DMC, celecoxib, and other coxibs and traditional NSAIDs indicated a correlation between the effects on survivin expression and cell survival or death.

Regulation (effects) of Gene_expression (expression) of survivin associated with cinod and death

3) Confidence 0.60 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.35 Pain Relevance 0.24

To determine whether survivin expression was similarly affected by these drugs, we generated cells that were stably transfected with luciferase reporter constructs under the control of the survivin promoter.

Spec (whether) Regulation (affected) of Spec (whether) Gene_expression (expression) of survivin

4) Confidence 0.60 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.31 Pain Relevance 0.16

We validated that the expression of Caspase 8, Fas and Birc5 genes was altered by real time RT-PCR (Figure 5).

Regulation (altered) of Gene_expression (expression) of Birc5

5) Confidence 0.47 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2610035 Disease Relevance 0.91 Pain Relevance 0

Overall, survivin expression is restricted during fetal development to NPCs in neurogenic regions of the telencephalon, of which a fraction populates the major neurogenic regions of the postnatal brain, i.e. the SVZ and the SGZ.

Regulation (restricted) of Gene_expression (expression) of survivin in neurogenic regions

6) Confidence 0.45 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2817683 Disease Relevance 0 Pain Relevance 0.03

Effect of gene therapy on the expression of survivin.

Regulation (Effect) of Gene_expression (expression) of survivin

7) Confidence 0.44 Published 2010 Journal Diabetes Section Body Doc Link PMC2797944 Disease Relevance 1.07 Pain Relevance 0

In addition, survivin exression was also regulated by FAK phosphorylation.

Regulation (regulated) of Gene_expression (exression) of survivin

8) Confidence 0.44 Published 2009 Journal Mol Cancer Section Body Doc Link PMC2806309 Disease Relevance 0.93 Pain Relevance 0

As shown in Figure 1, both drugs were able to down-regulate survivin expression in all cell lines investigated, which included cells derived from glioblastoma, lymphoma, multiple myeloma, and carcinoma of the breast, colon, and prostate.

Regulation (regulate) of Gene_expression (expression) of survivin in colon associated with lymphatic system cancer, glioblastoma, multiple myeloma and reprotox - general 1

9) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 1.28 Pain Relevance 0

It has been shown in several other experimental systems that the down-regulation of survivin expression, for example by antisense or siRNA approaches [65], results in elevated "basal level" apoptosis and, perhaps more importantly, causes substantially increased sensitivity of such tumor cells to killing by chemotherapeutic drugs or ionizing radiation (for examples, see [66-71]).

Regulation (regulation) of Gene_expression (expression) of survivin associated with cancer and apoptosis

10) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.81 Pain Relevance 0

However, in our study, there was no difference in survivin expression according to anatomic site, and no correlation between survivin expression and prognosis in biliary tract cancer.

Neg (no) Regulation (correlation) of Gene_expression (expression) of survivin in biliary tract associated with biliary cancer

11) Confidence 0.44 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2974735 Disease Relevance 1.35 Pain Relevance 0

Thus, we surmise that in addition to the transcriptional down-regulation of survivin expression, DMC and celecoxib also cause its increased posttranslational degradation via the elimination of CDK enzymatic activity.

Regulation (regulation) of Gene_expression (expression) of survivin

12) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.12 Pain Relevance 0

While the underlying molecular mechanisms have not been delineated, it is reasonable to consider that alterations in embryonic NPC survivin expression might contribute to those phenotypic changes.

Regulation (alterations) of Gene_expression (expression) of survivin

13) Confidence 0.27 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2817683 Disease Relevance 1.04 Pain Relevance 0.06

Suppression of survivin is specific to these two drugs, as other coxibs (valdecoxib, rofecoxib) or traditional NSAIDs (flurbiprofen, indomethacin, sulindac) do not affect survivin expression at similar concentrations.

Neg (not) Regulation (affect) of Gene_expression (expression) of survivin associated with cinod

14) Confidence 0.26 Published 2006 Journal Mol Cancer Section Abstract Doc Link PMC1479836 Disease Relevance 0.87 Pain Relevance 0.10

To determine whether celecoxib and DMC would be able to affect survivin expression in a variety of human tumor types, we treated a collection of derived cell lines with either drug in vitro.

Spec (whether) Regulation (affect) of Gene_expression (expression) of survivin associated with cancer

15) Confidence 0.26 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 1.04 Pain Relevance 0

These results are also consistent with our observation (Figure 3) that those NSAIDs that did not affect survivin expression (rofecoxib, valdecoxib, flurbiprofen, and others) also did not impinge on cell growth and survival and did not induce apoptosis.

Neg (not) Regulation (affect) of Gene_expression (expression) of survivin associated with cinod and apoptosis

16) Confidence 0.26 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1479836 Disease Relevance 0.78 Pain Relevance 0.10

In conclusion, our research demonstrates for the first time that both constitutive and LN-induced FAK phosphorylation contribute to increased intrinsic chemoresistance to Gem in pancreatic cancer cell lines and these effects are partly due to the regulation of Akt and Bad phosphorylation and survivin expression.

Regulation (regulation) of Gene_expression (expression) of survivin associated with pancreatic cancer

17) Confidence 0.26 Published 2009 Journal Mol Cancer Section Abstract Doc Link PMC2806309 Disease Relevance 0.37 Pain Relevance 0

In the present study, while 34.6% of tumors expressed p53, there was no correlation between p53 and survivin expression.

Neg (no) Regulation (correlation) of Gene_expression (expression) of survivin associated with cancer

18) Confidence 0.07 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1266027 Disease Relevance 1.02 Pain Relevance 0

In the present study, while 84.6% of tumors expressed Bax, there was no correlation between its expression and survivin expression or clinico-pathological parameters.

Neg (no) Regulation (correlation) of Gene_expression (expression) of survivin associated with cancer

19) Confidence 0.07 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1266027 Disease Relevance 1.13 Pain Relevance 0

Of forty-nine cases of pancreatic cancer, 46 cases (93.9%) were positive for survivin expression (Fig. 1).

Regulation (positive) of Gene_expression (expression) of survivin associated with pancreatic cancer

20) Confidence 0.07 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1266027 Disease Relevance 0.30 Pain Relevance 0

General Comments

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