INT20603

Context Info Confidence 0.67 First Reported 1983 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 40 Total Number 40 Disease Relevance 32.61 Pain Relevance 11.44

plasma membrane (TNFRSF10B)

Anatomy Link Frequency chondrocyte 1 colon 1 cleavage 1 LAK cell 1 LGL 1 TNFRSF10B (Homo sapiens)

Pain Link Frequency Relevance Heat agonist 269 99.82 qutenza 62 99.70 Enkephalin 30 99.32 cytokine 28 98.76 Arthritis 55 98.64 Morphine 3 98.64 cINOD 90 98.54 tramadol 7 98.16 antagonist 220 97.00 opioid receptor 1 96.52

Disease Link Frequency Relevance Heat Death 358 100.00 Apoptosis 1753 99.90 Stress 28 99.64 Glioma 36 99.40 Rheumatoid Arthritis 77 98.64 Reprotox - General 1 53 98.28 Renal Cancer 21 97.20 Cancer 942 96.92 Necrosis 35 96.68 Colon Cancer 189 96.64

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Sulindac sulfide up-regulated DR5 and activated the proximal caspase 8 in various different colon and prostate cancer cell lines.

Positive_regulation (regulated) of DR5 in colon associated with reprotox - general 1

1) Confidence 0.67 Published 2001 Journal Cancer Res. Section Abstract Doc Link 11559570 Disease Relevance 1.39 Pain Relevance 0.08

Induction of apoptosis by pectenotoxin-2 is mediated with the induction of DR4/DR5, Egr-1 and NAG-1, activation of caspases and modulation of the Bcl-2 family in p53-deficient Hep3B hepatocellular carcinoma cells.

Positive_regulation (induction) of DR5 associated with hepatocellular cancer, apoptosis and cytokine

2) Confidence 0.67 Published 2008 Journal Oncol. Rep. Section Title Doc Link 18202802 Disease Relevance 0.94 Pain Relevance 0.05

SC-'236 also upregulates DR5 in both Bax-proficient and Bax-deficient cells but Apo2L/TRAIL potentiates SC-'236-mediated apoptosis and caspases-8 and -3 activation in both Bax-proficient and Bax-deficient cells.

Positive_regulation (upregulates) of DR5 associated with apoptosis

3) Confidence 0.67 Published 2002 Journal Oncogene Section Abstract Doc Link 12203115 Disease Relevance 1.12 Pain Relevance 0.36

We further show that sulindac sulfide and SC-'236-induced DR5 upregulation occurs independent of the COX inhibitory effects of these NSAIDs.

Positive_regulation (upregulation) of DR5 associated with cinod

4) Confidence 0.67 Published 2002 Journal Oncogene Section Abstract Doc Link 12203115 Disease Relevance 1.06 Pain Relevance 0.46

We show that sulindac sulfide and SC-'236-induced apoptosis is coupled with upregulation of DR5, caspase 8 activation and Bid cleavage.

Positive_regulation (upregulation) of DR5 in cleavage associated with apoptosis

5) Confidence 0.67 Published 2002 Journal Oncogene Section Abstract Doc Link 12203115 Disease Relevance 1.02 Pain Relevance 0.46

For example, sulindac sulfide upregulates DR5 in both Bax-deficient and proficient cells, but Apo2L/TRAIL efficiently potentiates sulindac sulfide-induced apoptosis as well as activation of caspase-8, -9 and -3 only in Bax-proficient cells.

Positive_regulation (upregulates) of DR5 associated with apoptosis

6) Confidence 0.58 Published 2002 Journal Oncogene Section Abstract Doc Link 12203115 Disease Relevance 1.08 Pain Relevance 0.40

Sulindac sulfide specifically up-regulated the DR5 levels but had no effect on the levels of other DRs including DR4, Fas, and tumor necrosis factor receptor 1.

Positive_regulation (up-regulated) of DR5 associated with necrosis and cancer

7) Confidence 0.49 Published 2001 Journal Cancer Res. Section Abstract Doc Link 11559570 Disease Relevance 1.59 Pain Relevance 0.07

The salient points of various stages of this study are: low frequency of HLA-B14 antigen with, in contrast, high frequency of the HLA-DR5 antigen of the major histocompatibility system.

Positive_regulation (frequency) of DR5

8) Confidence 0.49 Published 1990 Journal Ann. Ital. Med. Int. Section Abstract Doc Link 2150489 Disease Relevance 0.68 Pain Relevance 0.68

These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone.

Positive_regulation (enhances) of NK in LGL associated with narcan and opioid receptor

9) Confidence 0.49 Published 1986 Journal J. Immunol. Section Abstract Doc Link 2934481 Disease Relevance 0 Pain Relevance 0.26

At effector:target cell ratios of 100:1, 33:1 and 11:1 leucine-enkephalin significantly (p less than 0.05) enhanced NK activity at dilutions of 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml.

Positive_regulation (enhanced) of NK associated with enkephalin

10) Confidence 0.49 Published 1987 Journal Nat. Immun. Cell Growth Regul. Section Abstract Doc Link 3600678 Disease Relevance 0.25 Pain Relevance 0.69

The enhancement of NK activity with beta-endorphin increased at all E:T ratios tested.

Positive_regulation (enhancement) of NK

11) Confidence 0.49 Published 1983 Journal J. Immunol. Section Abstract Doc Link 6300232 Disease Relevance 0 Pain Relevance 0.68

At effector:target cell ratios of 11:1 methionine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml, while leucine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-4), 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml.

Positive_regulation (enhanced) of NK associated with enkephalin

12) Confidence 0.49 Published 1984 Journal Clin. Immunol. Immunopathol. Section Abstract Doc Link 6713744 Disease Relevance 0 Pain Relevance 0.69

In fact, both doses of tramadol were able to prevent surgery-induced NK activity suppression, while the drug significantly increased NK activity in normal non-operated animals.

Positive_regulation (increased) of NK associated with tramadol

13) Confidence 0.45 Published 2002 Journal J. Neuroimmunol. Section Abstract Doc Link 12161016 Disease Relevance 0.30 Pain Relevance 1.14

At effector:target cell ratios of 11:1 methionine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml, while leucine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-4), 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml.

Positive_regulation (enhanced) of NK associated with enkephalin

14) Confidence 0.45 Published 1984 Journal Clin. Immunol. Immunopathol. Section Abstract Doc Link 6713744 Disease Relevance 0 Pain Relevance 0.70

It was suggested that the clinical response would be expected in case of increasing of CD16 cells or CD25 cells and augmentation of NK or LAK activity.

Positive_regulation (augmentation) of NK

15) Confidence 0.45 Published 1993 Journal Nippon Hinyokika Gakkai Zasshi Section Abstract Doc Link 8320888 Disease Relevance 0.75 Pain Relevance 0.08

indicating a critical role of DR5 induction in this death process.

Positive_regulation (induction) of DR5 associated with death

16) Confidence 0.35 Published 2008 Journal PPAR Research Section Body Doc Link PMC2442903 Disease Relevance 1.07 Pain Relevance 0.06

ligands to induce DR5 or downregulate c-FLIP [34].

Positive_regulation (induce) of DR5

17) Confidence 0.35 Published 2008 Journal PPAR Research Section Body Doc Link PMC2442903 Disease Relevance 0.72 Pain Relevance 0.18

Given that sulindac sulfide activated caspase-8 and increased membrane death receptor (DR4 and DR5) protein levels, we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Positive_regulation (increased) of DR5 associated with necrosis, cancer, apoptosis and death

18) Confidence 0.34 Published 2005 Journal Mol. Cancer Ther. Section Abstract Doc Link 16227396 Disease Relevance 1.40 Pain Relevance 0.12

Overexpression of DR5 receptor and its ligand (TRAIL) in chondrocyte-like cells suggested activation of programmed cell death, as also demonstrated by TUNEL-positive cells.

Positive_regulation (Overexpression) of DR5 receptor in chondrocyte associated with apoptosis

19) Confidence 0.33 Published 2009 Journal Histol. Histopathol. Section Abstract Doc Link 19130398 Disease Relevance 0.66 Pain Relevance 0.15

Figure 6 shows that although wild-type DREAM causes activation of the DR3- and DR5-containing promoters, DREAM mutants bearing the mutations L47,52V in the first LCD or L155V in the second LCD did not activate basal or ligand-dependent expression of the DR3 and RAR?

Positive_regulation (activation) of DR5-containing

20) Confidence 0.31 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0.13 Pain Relevance 0

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