INT57162

Context Info Confidence 0.68 First Reported 1994 Last Reported 2010 Negated 1 Speculated 1 Reported most in Abstract Documents 64 Total Number 66 Disease Relevance 35.30 Pain Relevance 9.69

cytosol (CDKN1A) nucleoplasm (CDKN1A) nucleus (CDKN1A) cell cycle (CDKN1A) kinase activity (CDKN1A) cytoplasm (CDKN1A)

Anatomy Link Frequency epithelial cell 6 BxPC-3 6 AGS 6 HPAC 5 Capan-2 4 CDKN1A (Homo sapiens)

Pain Link Frequency Relevance Heat agonist 64 99.98 dexamethasone 32 99.88 narcan 63 99.70 aspirin 32 99.56 antagonist 51 98.76 fibrosis 33 98.74 palliative 6 98.60 cocaine 584 98.36 Opioid 91 98.32 fluoxetine 22 97.44

Disease Link Frequency Relevance Heat Apoptosis 615 100.00 Hyperplasia 26 100.00 Rheumatoid Arthritis 58 99.98 Reprotox - General 1 37 99.72 Adenocarcinoma 54 99.64 Alagille Syndrome 8 99.18 Pulmonary Disease 130 99.12 Renal Cancer 9 98.84 Hypocalcemia 3 98.84 Leukemia 89 98.82

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Mutation

Event

Anatomy

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Disease term

We have found that p53 protein accumulated in a dose- and time-dependent manner after Dx treatment, while p21 expression increased over time with low but decreased with high Dx doses.

Positive_regulation (increased) of Gene_expression (expression) of p21

1) Confidence 0.68 Published 2002 Journal Carcinogenesis Section Abstract Doc Link 12151346 Disease Relevance 1.40 Pain Relevance 0.18

Higher concentrations of indomethacin and dexamethasone also up-regulated p21Cip1/Waf1 expression in hBMSCs, and so did celecoxib on D1-cells.

Positive_regulation (up-regulated) of Gene_expression (expression) of p21Cip1/Waf1 associated with dexamethasone

2) Confidence 0.67 Published 2007 Journal Biochem. Pharmacol. Section Abstract Doc Link 17714695 Disease Relevance 0.18 Pain Relevance 0.84

induced p21waf1 expression in PANC-1 cells, along with subsequent growth inhibition [21].

Positive_regulation (induced) of Gene_expression (expression) of p21 in PANC-1

3) Confidence 0.67 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2253554 Disease Relevance 0.76 Pain Relevance 0

We observed that IR-induced bax and p21(WAF1/Cip1) protein expression were attenuated selectively in normal stromal and epithelial cell cultures, yet maintained their p53-dependency in malignant cell lines.

Positive_regulation (induced) of Gene_expression (expression) of p21 in epithelial cell associated with malignant neoplastic disease

4) Confidence 0.67 Published 2003 Journal Prostate Cancer Prostatic Dis. Section Abstract Doc Link 12664070 Disease Relevance 0.91 Pain Relevance 0.10

Ectopic overexpression of p21Cip1 or p27KiP1 markedly enhanced the apoptosis induced by sulindac sulfide.

Positive_regulation (overexpression) of Gene_expression (overexpression) of p21Cip1 associated with apoptosis

5) Confidence 0.67 Published 2001 Journal Anticancer Res. Section Abstract Doc Link 11724286 Disease Relevance 0.81 Pain Relevance 0.13

Overexpression of PKCbeta(1) attenuated the apoptotic response of AGS cells to SC-236 and was associated with overexpression of p21(waf1/cip1).

Positive_regulation (overexpression) of Gene_expression (overexpression) of p21 in AGS associated with alagille syndrome and apoptosis

6) Confidence 0.67 Published 2002 Journal Oncogene Section Abstract Doc Link 12203123 Disease Relevance 0.90 Pain Relevance 0.21

Interestingly, upregulation of p21cip1 has been reported in the lung tissues of patients with pulmonary fibrosis, primarily in hyperplastic alveolar epithelial cells [27] The increased expression of p21cip1 can favour the process of epithelial cell apoptosis.

Positive_regulation (increased) of Gene_expression (expression) of p21cip1 in epithelial cell associated with fibrosis, pulmonary fibrosis, apoptosis and hyperplasia

7) Confidence 0.67 Published 2010 Journal Orphanet J Rare Dis Section Body Doc Link PMC2939531 Disease Relevance 1.07 Pain Relevance 0.08

Inhibition of PKCbeta(1)-mediated overexpression of p21(waf1/cip1) partially reduced the anti-apoptotic effect of PKCbeta(1).

Positive_regulation (overexpression) of Gene_expression (overexpression) of waf1 associated with apoptosis

8) Confidence 0.67 Published 2002 Journal Oncogene Section Abstract Doc Link 12203123 Disease Relevance 0.89 Pain Relevance 0.19

The finding was associated to increased levels of some CDKIs, namely p27(Kip1) and p21(Cip1), whereas ASA did not affected p16(Ink4A) level at any of the concentrations employed.

Positive_regulation (increased) of Gene_expression (levels) of Cip1 associated with aspirin

9) Confidence 0.49 Published 2008 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 19144277 Disease Relevance 0.13 Pain Relevance 0.51

The finding was associated to increased levels of some CDKIs, namely p27(Kip1) and p21(Cip1), whereas ASA did not affected p16(Ink4A) level at any of the concentrations employed.

Positive_regulation (increased) of Gene_expression (levels) of p21 associated with aspirin

10) Confidence 0.49 Published 2008 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 19144277 Disease Relevance 0.13 Pain Relevance 0.51

Antisense p21 ODN transfection of MDCK cells at 400 and 600 nM showed increased cell proliferation as compared to cells transfected with scrambled control ODN (Fig. 5b).

Positive_regulation (Antisense) of Gene_expression (transfection) of p21 in MDCK

11) Confidence 0.49 Published 2007 Journal BMC Nephrol Section Body Doc Link PMC2045080 Disease Relevance 0.27 Pain Relevance 0

Inhibition of PKCbeta(1)-mediated overexpression of p21(waf1/cip1) partially reduced the anti-apoptotic effect of PKCbeta(1).

Positive_regulation (overexpression) of Gene_expression (overexpression) of p21 associated with apoptosis

12) Confidence 0.49 Published 2002 Journal Oncogene Section Abstract Doc Link 12203123 Disease Relevance 0.89 Pain Relevance 0.19

Studies have shown, that characteristic genetic changes of the invasive ductal carcinoma such like p53 mutations and the loss DPC4/SMAD4 are a late event in the PanIN development whereas the overexpression of p21WAF1/CIP1 is an early event in the precursor lesions [26].

Positive_regulation (overexpression) of Gene_expression (overexpression) of CIP1 associated with ductal carcinoma

13) Confidence 0.49 Published 2003 Journal Mol Cancer Section Body Doc Link PMC149423 Disease Relevance 1.26 Pain Relevance 0.06

We observed that IR-induced bax and p21(WAF1/Cip1) protein expression were attenuated selectively in normal stromal and epithelial cell cultures, yet maintained their p53-dependency in malignant cell lines.

Positive_regulation (attenuated) of Gene_expression (expression) of WAF1 in epithelial cell associated with malignant neoplastic disease

14) Confidence 0.49 Published 2003 Journal Prostate Cancer Prostatic Dis. Section Abstract Doc Link 12664070 Disease Relevance 0.91 Pain Relevance 0.10

Interestingly, a recent study investigating the mechanisms underlying the PI3K-mediated suppression of PMA-induced expression of p21WAF1/Cip1 showed that blocking of the PI3K/mTOR pathway was associated with increased binding by Sp1 [38].

Positive_regulation (induced) of Gene_expression (expression) of Cip1

15) Confidence 0.49 Published 2008 Journal Cell Signal Section Body Doc Link PMC2586094 Disease Relevance 0.13 Pain Relevance 0.03

Higher concentrations of indomethacin and dexamethasone also up-regulated p21Cip1/Waf1 expression in hBMSCs, and so did celecoxib on D1-cells.

Positive_regulation (up-regulated) of Gene_expression (expression) of p21Cip1/Waf1 associated with dexamethasone

16) Confidence 0.49 Published 2007 Journal Biochem. Pharmacol. Section Abstract Doc Link 17714695 Disease Relevance 0.18 Pain Relevance 0.84

Overexpression of PKCbeta(1) attenuated the apoptotic response of AGS cells to SC-236 and was associated with overexpression of p21(waf1/cip1).

Positive_regulation (overexpression) of Gene_expression (overexpression) of waf1 in AGS associated with alagille syndrome and apoptosis

17) Confidence 0.49 Published 2002 Journal Oncogene Section Abstract Doc Link 12203123 Disease Relevance 0.90 Pain Relevance 0.21

p21(Waf1/Cip1/Sdi1) is the primary mediator of cell cycle arrest in response to different forms of stress and in the programs of senescence and differentiation. p21 interacts with many regulatory proteins and has broad effects on cellular gene expression. p21 was previously shown to stimulate NFkappaB transcriptional activity through its effect on the p300/CBP transcription cofactor family. p21 expression in human cells increases mRNA levels of different genes, some of which have been implicated in carcinogenesis and age-related diseases.

Positive_regulation (increases) of Gene_expression (expression) of p21 associated with stress, aging and disease

18) Confidence 0.47 Published 2004 Journal Cell Cycle Section Abstract Doc Link 15190207 Disease Relevance 0.44 Pain Relevance 0.07

Doxorubicin (Dx), an anthracycline used commonly as a chemotherapeutic agent in relapsed prostate cancer, is a strong inducer of p53 expression and p21(CIP1/WAF1) (p21) transactivation.

Positive_regulation (inducer) of Gene_expression (expression) of p21 associated with reprotox - general 1

19) Confidence 0.46 Published 2002 Journal Carcinogenesis Section Abstract Doc Link 12151346 Disease Relevance 0.99 Pain Relevance 0.16

Inhibition of PKC-beta1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta1.

Positive_regulation (overexpression) of Gene_expression (overexpression) of cip1

20) Confidence 0.45 Published 2000 Journal Gastroenterology Section Body Doc Link 10702201 Disease Relevance 0.07 Pain Relevance 0

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