INT104330

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Context Info
Confidence 0.58
First Reported 2002
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 57
Total Number 59
Disease Relevance 39.93
Pain Relevance 5.88

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

cytosol (CDKN1A) nucleoplasm (CDKN1A) nucleus (CDKN1A)
cell cycle (CDKN1A) kinase activity (CDKN1A) cytoplasm (CDKN1A)
Anatomy Link Frequency
MDCK 2
OVCAR-3 2
smooth muscle cells 1
HGF 1
tubules 1
CDKN1A (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 89 99.80 Very High Very High Very High
antagonist 36 96.16 Very High Very High Very High
withdrawal 30 93.52 High High
COX-2 inhibitor 53 84.68 Quite High
Opioid 45 75.00 Quite High
narcan 27 67.48 Quite High
metalloproteinase 15 64.96 Quite High
Inflammation 83 60.52 Quite High
Enkephalin 8 57.12 Quite High
palliative 3 57.04 Quite High
Disease Link Frequency Relevance Heat
Disease 691 99.92 Very High Very High Very High
Polycystic Kidney Disease 828 99.84 Very High Very High Very High
Targeted Disruption 102 99.64 Very High Very High Very High
Reprotox - General 1 26 99.56 Very High Very High Very High
Suicidal Behaviour 81 99.22 Very High Very High Very High
Prostate Cancer 36 99.20 Very High Very High Very High
Apoptosis 1421 99.08 Very High Very High Very High
Hypertrophy 24 98.56 Very High Very High Very High
Pancreatic Cancer 121 98.20 Very High Very High Very High
Cancer 837 98.18 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Reduction of p21 levels in prostate cancer cells with an antisense p21 adenovirus resulted in sensitization to Dx and accelerated onset of apoptosis in response to growth factor withdrawal.
Negative_regulation (Reduction) of p21 associated with apoptosis, withdrawal and reprotox - general 1
1) Confidence 0.58 Published 2002 Journal Carcinogenesis Section Abstract Doc Link 12151346 Disease Relevance 1.39 Pain Relevance 0.18
We now show that p21 is consistently downregulated in all models examined.
Negative_regulation (downregulated) of p21
2) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.73 Pain Relevance 0
This discrepancy may be explained by the pleiotropic effects of p21, as well as the stage at which p21 is inhibited: it is possible that a decrease in p21 levels in early stages of the disease allows RTEs to grow and form cysts via its cyclin/cdk inhibitor function, whereas mTOR inhibitors may be useful in later stages of the disease to decrease p21 and thereby attenuate cell growth via its assembly factor role [20].
Spec (possible) Negative_regulation (decrease) of p21 associated with cyst and disease
3) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.30 Pain Relevance 0
These observations are consistent with the hypothesis that suppression of p21 may play at least a permissive role in cystogenesis
Negative_regulation (suppression) of p21
4) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.55 Pain Relevance 0
This discrepancy may be explained by the pleiotropic effects of p21, as well as the stage at which p21 is inhibited: it is possible that a decrease in p21 levels in early stages of the disease allows RTEs to grow and form cysts via its cyclin/cdk inhibitor function, whereas mTOR inhibitors may be useful in later stages of the disease to decrease p21 and thereby attenuate cell growth via its assembly factor role [20].
Negative_regulation (decrease) of p21 associated with cyst and disease
5) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.25 Pain Relevance 0
While investigation in non-cancer cell lines has not to our knowledge been reported, other investigators have shown a small decrease in p21 levels in vitro in prostate tumor spheroids [30].
Negative_regulation (decrease) of p21 associated with cancer and prostate cancer
6) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.00 Pain Relevance 0
Therefore, a decreased cytosolic p21 may result in inducing apoptosis which is the same effect as caspase inhibition [38].
Negative_regulation (decreased) of p21 associated with apoptosis
7) Confidence 0.57 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.15 Pain Relevance 0
Addition of exogenous BMP-6 to DU-145 prostate cancer cell cultures inhibited their growth by up-regulation of several cyclin-dependent kinase inhibitors such as p21/CIP, p18, and p19.
Negative_regulation (inhibitors) of p21 associated with reprotox - general 1
8) Confidence 0.57 Published 2004 Journal Cancer Res. Section Abstract Doc Link 15548695 Disease Relevance 0.59 Pain Relevance 0.14
Furthermore, we observed down-regulation of p21 WAF1/CIP1 by introduction of NAG-1 small interfering RNA into sulindac sulfide-treated cells.
Negative_regulation (regulation) of WAF1
9) Confidence 0.57 Published 2005 Journal Mol. Cancer Ther. Section Abstract Doc Link 15767558 Disease Relevance 0.57 Pain Relevance 0.41
Other essential regulators of the cell cycle are the cyclin-dependent kinase (CDK) inhibitors, such as p21Cip1 and p27Kip1, which have inhibitory effects on several CDKs [26,27].
Negative_regulation (inhibitors) of p21Cip1
10) Confidence 0.57 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2914703 Disease Relevance 0 Pain Relevance 0
In parallel to the NSAID-mediated reduction of CDK-2 activity, p21(cip-1) promoter activity and cellular p21(cip-1) levels increased and p21(cip-1) was sequestered into CDK-2 complexes.
Negative_regulation (reduction) of cip-1 associated with cinod
11) Confidence 0.43 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566837 Disease Relevance 0.38 Pain Relevance 0.60
In parallel to the NSAID-mediated reduction of CDK-2 activity, p21(cip-1) promoter activity and cellular p21(cip-1) levels increased and p21(cip-1) was sequestered into CDK-2 complexes.
Negative_regulation (reduction) of cip-1 associated with cinod
12) Confidence 0.43 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566837 Disease Relevance 0.38 Pain Relevance 0.61
In parallel to the NSAID-mediated reduction of CDK-2 activity, p21(cip-1) promoter activity and cellular p21(cip-1) levels increased and p21(cip-1) was sequestered into CDK-2 complexes.
Negative_regulation (reduction) of p21 associated with cinod
13) Confidence 0.43 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566837 Disease Relevance 0.38 Pain Relevance 0.61
Thus, the G1 arrest likely resulted from p21(cip-1)-dependent inhibition of CDK-2 activity.
Negative_regulation (inhibition) of cip-1
14) Confidence 0.42 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566837 Disease Relevance 0.36 Pain Relevance 0.59
Thus, the G1 arrest likely resulted from p21(cip-1)-dependent inhibition of CDK-2 activity.
Negative_regulation (inhibition) of p21
15) Confidence 0.42 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566837 Disease Relevance 0.36 Pain Relevance 0.59
One of these pathways involves key arbiters of cell cycle progression and apoptosis, the cyclins, their associated kinases, and the cyclin kinase inhibitors, of which group p21 is a member.
Negative_regulation (inhibitors) of p21 associated with apoptosis
16) Confidence 0.42 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.53 Pain Relevance 0
The increase in p21 with scrambled control ODN was likely a result of non-specific cellular stress and 600 nM ODNs are more toxic to cells than 400 nM, showing the overall lower proliferation rate; however, the levels of p21 (Fig. 5a) correspond inversely with cell proliferation (Fig. 5b), consistent with the established cell cycle inhibitory effect of p21, and supporting our hypothesis that decreased p21 as seen in PKD is associated with increased RTE proliferation.
Negative_regulation (decreased) of p21 associated with stress
17) Confidence 0.42 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.17 Pain Relevance 0
Since we have now shown that p21 possesses an anti-proliferative, and hence likely anti-cystic, effect on the cystogenic MDCK cell line, and that p21 is decreased in human ADPKD, it is possible that the p21 pathway, including the p21waf1 gene, may be utilized in future therapy of this disease with or without the addition of another CDK inhibitor such as roscovitine which itself increases p21.
Negative_regulation (decreased) of p21 in MDCK associated with polycystic kidney disease and disease
18) Confidence 0.42 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.83 Pain Relevance 0
However, our finding that p21 is decreased in ADPKD, while in agreement with earlier studies showing that PKD1-deficient cells express lower p21, is not in complete concordance with the mTOR inhibitor data.
Negative_regulation (decreased) of p21 associated with polycystic kidney disease
19) Confidence 0.42 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 1.35 Pain Relevance 0
While this data is consistent with our finding that p21 is decreased in cystic tissue, whether HGF lies within the polycystin 1 ?
Negative_regulation (decreased) of p21 in HGF
20) Confidence 0.42 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.33 Pain Relevance 0

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