INT112868

Context Info Confidence 0.75 First Reported 2003 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 21 Total Number 22 Disease Relevance 8.60 Pain Relevance 2.15

nucleus (Pcna) intracellular (Pcna) DNA binding (Pcna) transcription factor binding (Pcna) cytoplasm (Pcna)

Anatomy Link Frequency HPAC 1 BxPC-3 1 apoptotic cell 1 epithelium 1 respiratory 1 Pcna (Mus musculus)

Pain Link Frequency Relevance Heat agonist 21 99.70 Paracetamol 22 99.12 Inflammation 53 93.40 Neuritis 1 79.88 cINOD 1 78.24 antagonist 25 77.36 cerebral cortex 73 58.72 metalloproteinase 36 41.84 Hippocampus 8 13.44 cytokine 10 6.48

Disease Link Frequency Relevance Heat Apoptosis 799 99.54 Cancer 209 98.92 INFLAMMATION 57 93.40 Neurodegenerative Disease 68 92.48 Hepatotoxicity 3 91.56 Sprains And Strains 8 90.36 Pancreatic Cancer 90 89.64 Adhesions 47 89.36 Suicidal Behaviour 216 86.80 Lung Cancer 5 81.52

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Expression of proliferating cell nuclear antigen (PCNA) and cell cycle proteins cyclin D1 and p21 were not detectable in controls or after AAP alone.

Gene_expression (Expression) of proliferating cell nuclear antigen associated with paracetamol

1) Confidence 0.75 Published 2003 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12954812 Disease Relevance 0.43 Pain Relevance 0.74

Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2-deoxyguanosine; multigene expression, and thiobarbituric acid-reactive aldehydes in whole lung and several other organs.

Gene_expression (expression) of proliferating cell nuclear antigen in epithelium associated with apoptosis

2) Confidence 0.65 Published 2005 Journal Exp. Lung Res. Section Abstract Doc Link 15765917 Disease Relevance 0.57 Pain Relevance 0.08

Expression of proliferating cell nuclear antigen (PCNA) and cell cycle proteins cyclin D1 and p21 were not detectable in controls or after AAP alone.

Neg (not) Gene_expression (detectable) of proliferating cell nuclear antigen associated with paracetamol

3) Confidence 0.58 Published 2003 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12954812 Disease Relevance 0.42 Pain Relevance 0.75

The induction of proliferation in a subset of bronchiolar cells and alveolar type II cells by Sox17 was associated with increased expression of several cyclin genes known to stimulate cell cycle progression.

Gene_expression (expression) of cyclin

4) Confidence 0.24 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

Recent studies have shown that post-mitotic cells can reenter the cell cycle by blocking the expression of cyclin-dependent kinase inhibitors, supporting a role for this protein family in maintaining the balance between quiescence and proliferation [54].

Gene_expression (expression) of cyclin

5) Confidence 0.24 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.20 Pain Relevance 0

Together, these results demonstrate that Sox17 expression in adult mouse lung results in decreased levels of cyclin-dependent kinase inhibitors associated with G1 arrest and increased expression of cell cycle-promoting genes, providing insight into the molecular mechanisms that regulate Sox17-induced proliferation associated with the initiation of progenitor cell behavior in respiratory epithelial cells.

Gene_expression (expression) of cyclin in respiratory

6) Confidence 0.21 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

B activation operates on cell growth through cyclin expression is indicated in certain cell types [16].

Gene_expression (expression) of cyclin

7) Confidence 0.07 Published 2010 Journal Gastroenterology Research and Practice Section Body Doc Link PMC2995932 Disease Relevance 0.60 Pain Relevance 0.13

We therefore examined if Fas activation and estrogen could interact to regulate the expression of cyclin A, PCNA and p21/waf-1 and compared the expression of these anti-apoptotic cell cycle proteins with other cell-cycle proteins.

Gene_expression (expression) of cyclin in apoptotic cell associated with apoptosis

8) Confidence 0.05 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.58 Pain Relevance 0.03

We therefore hypothesized that in the context of Fas activation, estrogen would alter the expression of specific cell-cycle related proteins such as Cyclin-A [50], the Proliferating Cell Nuclear Antigen (PCNA, [51,52]) and p21/waf-1 [53], that also serve anti-apoptotic and DNA repair functions in addition to their roles in cell cycle.

Gene_expression (expression) of Cyclin associated with apoptosis

9) Confidence 0.05 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.49 Pain Relevance 0.07

In contrast, estrogen and sFasL, individually and together, induced cyclin-A expression, suggesting activation of compensatory survival mechanisms.

Gene_expression (expression) of cyclin

10) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Abstract Doc Link PMC395829 Disease Relevance 0.53 Pain Relevance 0

nor sFasL alone or together altered the expression of cdk2 or cyclin E compared to control cultures (Figure 9).

Gene_expression (expression) of cyclin

11) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.31 Pain Relevance 0

Similarly, neither estrogen nor sFasL significantly altered the expression of Cyclin-dependent Kinase-1 (cdk1/cdc2) relative to control cultures, suggesting that that interactions between estrogen and Fas activation were not specifically related to cell cycle.

Gene_expression (expression) of Cyclin

12) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.28 Pain Relevance 0

Therefore, we examined the expression of cyclin-A following exposure to E2 and/or FasL.

Spec (examined) Gene_expression (expression) of cyclin

13) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.22 Pain Relevance 0

Estrogen and sFasL separately and together induce expression of cyclin A.

Gene_expression (expression) of cyclin

14) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.27 Pain Relevance 0.03

Both estrogen and sFasL alone led to a statistically significant increase in the expression of cyclin-A compared with controls at 12 hours post-treatment.

Gene_expression (expression) of cyclin

15) Confidence 0.04 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.16 Pain Relevance 0

agonist increases the expression of the cyclin inhibitor p16, indicating that

Gene_expression (expression) of cyclin associated with agonist

16) Confidence 0.04 Published 2008 Journal PPAR Research Section Body Doc Link PMC2581793 Disease Relevance 0.24 Pain Relevance 0.17

Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression.

Gene_expression (expression) of Cyclin

17) Confidence 0.01 Published 2006 Journal Yonsei Medical Journal Section Abstract Doc Link PMC2687755 Disease Relevance 0.66 Pain Relevance 0.04

Thus, the reduction of Cyclin or Cdk expressions results the blocking of Cyclin-Cdk complexes formation and that lowers the level of phospho-Rb.

Gene_expression (expressions) of Cyclin

18) Confidence 0.01 Published 2006 Journal Yonsei Medical Journal Section Body Doc Link PMC2687755 Disease Relevance 0.61 Pain Relevance 0.03

Western blot analyses indicated that [6]-gingerol decreased the expression of Cyclin A and Cdks including Cdk2, Cdk4, and Cdk6 in BxPC-3.

Gene_expression (expression) of Cyclin in BxPC-3

19) Confidence 0.01 Published 2006 Journal Yonsei Medical Journal Section Body Doc Link PMC2687755 Disease Relevance 0.48 Pain Relevance 0.03

Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression.

Gene_expression (expression) of Cyclin

20) Confidence 0.01 Published 2006 Journal Yonsei Medical Journal Section Abstract Doc Link PMC2687755 Disease Relevance 0.67 Pain Relevance 0.04

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