INT84308

Context Info Confidence 0.75 First Reported 1999 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 12 Total Number 12 Disease Relevance 6.16 Pain Relevance 1.65

ATPase activity (Cftr) enzyme binding (Cftr) molecular_function (Cftr) protein complex (Cftr) transmembrane transport (Cftr) cytoplasm (Cftr)

Anatomy Link Frequency erythrocytes 1 CPAE 1 pancreas 1 nasal 1 epithelial cells 1 Cftr (Rattus norvegicus)

Pain Link Frequency Relevance Heat fibrosis 145 99.32 Inflammation 107 98.60 Chronic pancreatitis 8 95.32 adenocard 16 86.96 Prostatitis 204 81.12 fluoxetine 5 49.00 cytokine 40 40.96 ischemia 30 5.00 addiction 26 5.00 Bile 16 5.00

Disease Link Frequency Relevance Heat Pressure And Volume Under Development 146 99.74 Cystic Fibrosis 145 99.32 Cancer 14 99.28 INFLAMMATION 113 98.60 Infection 16 98.04 Appetite Loss 2 97.48 Reprotox - General 3 4 97.08 Adenocarcinoma 3 96.64 Targeted Disruption 10 96.24 Pancreatitis 55 96.04

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The key question is: are these neoplasms related to previously unrecognized functions of CFTR, or are they secondary to chronic inflammation, infection, or malnutrition, which might predispose to malignancy?

Localization (functions) of CFTR associated with appetite loss, malignant neoplastic disease, inflammation, cancer and infection

1) Confidence 0.75 Published 2000 Journal Respir Res Section Body Doc Link PMC59552 Disease Relevance 1.73 Pain Relevance 0.31

Involvement of CFTR in mediating prostatic bicarbonate secretion

Localization (secretion) of CFTR

2) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2998414 Disease Relevance 0.13 Pain Relevance 0.06

secretion, the CFTR-dependent bacterial killing capacity of the prostate could be due to a direct effect of HCO3?

Localization (secretion) of CFTR-dependent

3) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2998414 Disease Relevance 0.64 Pain Relevance 0.22

Immunofluorescent staining also localized CFTR protein to the plasma membrane of the culture epithelial cells (Figure 1D, right), which was also stained positive for cytokeratin 5&8, a marker of epithelial cells (Figure 1D, middle).

Localization (localized) of CFTR in epithelial cells

4) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2998414 Disease Relevance 0.20 Pain Relevance 0.10

However, given the striking increase of studies suggesting capability of CFTR to conduct large anions when they are present on the intracellular side and where ATP hydrolysis can occur [44], one may suppose that, in certain physiological conditions, even normally ATP-impermeable Cl?

Localization (capability) of CFTR

5) Confidence 0.39 Published 2005 Journal Purinergic Signal Section Body Doc Link PMC2096548 Disease Relevance 0.08 Pain Relevance 0.03

Interestingly, CFTR knockout animals, in which MRP1 expression was found to be augmented, had an increased rate of ATP release from unstimulated erythrocytes, suggesting that ATP release was mediated by MRP1 but not by CFTR.

Neg (not) Localization (by) of CFTR in erythrocytes associated with targeted disruption

6) Confidence 0.39 Published 2005 Journal Purinergic Signal Section Body Doc Link PMC2096548 Disease Relevance 0.15 Pain Relevance 0

CFTR-independent ATP release was observed by Takahashi et al. [54] in 3T3 fibroblasts, by Grygorczyk and Hanrahan [55] in T84, CHO, Calu-3, NIH3T3 and some other cells, by Mitchell et al. [56] in ocular ciliary epithelial cells, by Watt et al. [57] in human nasal epithelial cells in primary culture, by Hazama et al. [58–61] in human Intestine 407 and mouse C127 cells, and by Donaldson et al. [62] in nasal airway surface liquid from normal and CF subjects.

Localization (release) of CFTR-independent in fibroblasts associated with fibrosis

7) Confidence 0.37 Published 2005 Journal Purinergic Signal Section Body Doc Link PMC2096548 Disease Relevance 0.08 Pain Relevance 0.04

Heterologous expression of CFTR was shown to downregulate VSOR anion channel activity in CPAE and COS cells [116] as well as in HEK293T cells [117], but upregulate swelling-induced ATP release from C127/CFTR cells [58, 60].

Localization (release) of CFTR in CPAE associated with pressure and volume under development

8) Confidence 0.37 Published 2005 Journal Purinergic Signal Section Body Doc Link PMC2096548 Disease Relevance 0.57 Pain Relevance 0

Three features distinguish CF from controls: 1) higher basal PD, reflecting enhanced Na+ transport secondary to relative Cl- impermeability 2) greater inhibition of PD after nasal perfusion with amiloride, a Na+ channel inhibitor, and 3) little or no change in change of Cl- transport in response to perfusion with a Cl--free solution along with isoproteronol, (which reflects an absence of CFTR-mediated Cl- secretion).

Localization (secretion) of CFTR in nasal associated with fibrosis

9) Confidence 0.37 Published 2008 Journal J Med Case Reports Section Body Doc Link PMC2435544 Disease Relevance 0.85 Pain Relevance 0.35

If anionic forms of ATP are released via the CFTR channel, then actual ATP-mediated conductance should be measurable in CFTR-expressing cells under certain experimental conditions.

Localization (released) of CFTR

10) Confidence 0.34 Published 2005 Journal Purinergic Signal Section Body Doc Link PMC2096548 Disease Relevance 0.53 Pain Relevance 0.15

This article reviews the impact of CF on the pancreas, the role of the CFTR protein in pancreatic secretion, and some of the exciting research identifying mutations in the CFTR gene as a risk factor for idiopathic acute and chronic pancreatitis.

Localization (secretion) of CFTR in pancreas associated with fibrosis and chronic pancreatitis

11) Confidence 0.33 Published 1999 Journal Gastroenterol. Clin. North Am. Section Abstract Doc Link 10503135 Disease Relevance 1.22 Pain Relevance 0.39

Bioresponsive matrices in drug delivery For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type.

Localization (release) of controlling

12) Confidence 0.01 Published 2010 Journal J Biol Eng Section Title Doc Link PMC3002303 Disease Relevance 0 Pain Relevance 0

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