INT89794

Context Info Confidence 0.67 First Reported 2000 Last Reported 2011 Negated 0 Speculated 1 Reported most in Body Documents 58 Total Number 59 Disease Relevance 50.18 Pain Relevance 5.38

nucleoplasm (CDKN2A) DNA binding (CDKN2A) protein complex (CDKN2A) cytoplasm (CDKN2A) cytosol (CDKN2A) nucleolus (CDKN2A)

Anatomy Link Frequency telomere 3 SCC-4 2 pancreatic duct 2 CAL-27 2 impression 1 CDKN2A (Homo sapiens)

Pain Link Frequency Relevance Heat Opioid 15 99.22 opioid receptor 12 98.00 narcan 6 97.08 cytokine 74 96.60 abdominal pain 6 96.48 melanocortin 1 receptor 160 95.88 Osteoarthritis 103 93.68 tolerance 2 93.68 qutenza 130 93.28 COX-2 inhibitor 52 93.20

Disease Link Frequency Relevance Heat Cancer 1175 100.00 Acute Renal Failure 282 100.00 Melanoma 272 100.00 Death 93 100.00 Rhabdomyolysis 304 99.98 Sepsis 37 99.98 Necrosis 31 99.88 Poisoning 9 99.58 Apoptosis 381 99.56 Gastritis 3 99.40

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Histologic findings of a renal biopsy indicated that acute tubular necrosis (ATN) had caused ARF in this patient's case.

Positive_regulation (caused) of ARF associated with acute renal failure and necrosis

1) Confidence 0.67 Published 2000 Journal Am. J. Kidney Dis. Section Abstract Doc Link 10922331 Disease Relevance 1.26 Pain Relevance 0.16

-galactosidase activity [12], increase in reactive oxygen species (ROS), telomere attrition [13] and p53/p16ink4 accumulation [11].

Positive_regulation (accumulation) of p16ink4 in telomere

2) Confidence 0.67 Published 2010 Journal The Open Rheumatology Journal Section Body Doc Link PMC2845788 Disease Relevance 1.57 Pain Relevance 0.37

Under the impression of exercise-induced ARF, we tried to determine the relationship between the occurrence of clinical symptoms, renal dysfunction and the characteristic CT findings by observing those changes prospectively before and after anaerobic exercise.

Positive_regulation (induced) of ARF in impression associated with acute renal failure and renal disease

3) Confidence 0.67 Published 2006 Journal Clin. Nephrol. Section Abstract Doc Link 17063998 Disease Relevance 0.98 Pain Relevance 0.14

Inhibition of p16 (INK4a) activation by p16-specific siRNA blocked OGF's repressive action on proliferation of SCC-1, CAL-27, and SCC-4 HNSCC cells.

Positive_regulation (activation) of p16 in SCC-4

4) Confidence 0.65 Published 2007 Journal Cancer Res. Section Abstract Doc Link 17974995 Disease Relevance 0.21 Pain Relevance 0.24

Inhibition of p16 (INK4a) activation by p16-specific siRNA blocked OGF's repressive action on proliferation of SCC-1, CAL-27, and SCC-4 HNSCC cells.

Positive_regulation (activation) of INK4a in SCC-4

5) Confidence 0.65 Published 2007 Journal Cancer Res. Section Abstract Doc Link 17974995 Disease Relevance 0.21 Pain Relevance 0.24

Overexpression of p16 in the carcinomatous regions of MMMT (Figure 1E) with inverse expression of p21 in these regions denotes an upregulation of p16.

Positive_regulation (upregulation) of p16 associated with cancer

6) Confidence 0.63 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2913917 Disease Relevance 0.77 Pain Relevance 0

A number of studies have shown increased levels of p16INK4a with increased occurrence of senescence [32,33]. p16INK4a is thought to be involved in the activation of the retinoblastoma cell cycle inhibitory pathway, leading to permanent growth arrest and cellular senescence [34].

Positive_regulation (increased) of p16INK4a associated with aging and retinoblastoma

7) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.57 Pain Relevance 0

E6 inhibits p53 function by binding with E6-AP ubiquitin ligase, and leads to p14ARF upregulation via p53 degradation by negative feedback mechanism [22, 23].

Positive_regulation (upregulation) of p14ARF

8) Confidence 0.55 Published 2011 Journal Journal of Skin Cancer Section Body Doc Link PMC3003991 Disease Relevance 1.20 Pain Relevance 0

For pancreatic carcinoma, this disruption is caused exclusively by inactivation of p16INK4a gene and, only rarely, the Rb gene [24,25].

Positive_regulation (inactivation) of p16INK4a associated with pancreatic cancer

9) Confidence 0.50 Published 2005 Journal BMC Gastroenterol Section Body Doc Link PMC1185532 Disease Relevance 0.63 Pain Relevance 0

Inactivation of p16 gene occurs through intragenic mutation, homozygous deletion and methylation associated transcriptional silencing.

Positive_regulation (Inactivation) of p16

10) Confidence 0.50 Published 2005 Journal BMC Gastroenterol Section Body Doc Link PMC1185532 Disease Relevance 0.68 Pain Relevance 0

LOH could also be selected as the “second hit” for inactivating TP53 and CDKN2A.

Positive_regulation (inactivating) of CDKN2A

11) Confidence 0.50 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1808095 Disease Relevance 0.91 Pain Relevance 0

Genomic DNA from flow-purified Barrett's epithelium was evaluated for CDKN2A promoter methylation in 175 flow-purified fractions from 121 participants.

Positive_regulation (evaluated) of CDKN2A in epithelium

12) Confidence 0.50 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1808095 Disease Relevance 0.15 Pain Relevance 0

We found that both RHC and NRHC variants were associated with statistically significantly increased melanoma risk in CDKN2A mutation carriers, whereas a recent meta-analysis of melanoma case–control studies reported that most MC1R variants, except the most frequent NRHC variants, V60L and V92M, were associated with statistically significantly increased melanoma risk (12).

Positive_regulation (increased) of CDKN2A associated with melanocortin 1 receptor and melanoma

13) Confidence 0.49 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.04 Pain Relevance 0.37

This case highlights a case of selenium intoxication from selenite broth resulting in ARF and corrosive gastritis.

Positive_regulation (resulting) of ARF associated with acute renal failure, gastritis and poisoning

14) Confidence 0.49 Published 2009 Journal Saudi J Kidney Dis Transpl Section Abstract Doc Link 19112227 Disease Relevance 1.18 Pain Relevance 0.07

Importantly, p16 complexed with Cdk4 was increased by OGF treatment at all time points, consistent with the hypothesis that OGF mediated growth inhibition through p16.

Positive_regulation (increased) of p16

15) Confidence 0.47 Published 2007 Journal Cancer Res. Section Abstract Doc Link 17974995 Disease Relevance 0.23 Pain Relevance 0.26

Inactivating mutations, or loss, results in inactivation of the two encoding tumor suppressor genes p16 and p14.

Positive_regulation (inactivation) of p16 associated with cancer

16) Confidence 0.46 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 1.03 Pain Relevance 0

Here, we demonstrate for the first time that, in cells extracted from human NP tissue, increased levels of p16INK4a were associated with increased gene expression of the degradative enzymes MMP-13 and ADAMTS 5, which is characteristic of disc degeneration [5,39].

Positive_regulation (levels) of p16INK4a associated with intervertebral disk degeneration

17) Confidence 0.46 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.34 Pain Relevance 0.06

Importantly, this study has shown that degenerate discs exhibit accelerated senescence with decreased telomere length, reduced cell replication potential, and elevated levels of p16INK4a and SA-?

Positive_regulation (elevated) of p16INK4a in telomere associated with aging

18) Confidence 0.46 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.79 Pain Relevance 0

In particular, we have found that telomeric erosion increases with age together with increased levels of p16INK4a.

Positive_regulation (increased) of p16INK4a

19) Confidence 0.46 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.80 Pain Relevance 0

Here, we demonstrate for the first time that, in cells extracted from human NP tissue, increased levels of p16INK4a were associated with increased gene expression of the degradative enzymes MMP-13 and ADAMTS 5, which is characteristic of disc degeneration [5,39].

Positive_regulation (increased) of p16INK4a associated with intervertebral disk degeneration

20) Confidence 0.46 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.34 Pain Relevance 0.06

General Comments

This test has worked.