INT124042

Context Info Confidence 0.80 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 10 Disease Relevance 4.13 Pain Relevance 0.57

signal transduction (FGF7) extracellular space (FGF7) extracellular region (FGF7) Golgi apparatus (FGF7)

Anatomy Link Frequency keratinocytes 3 fibroblasts 2 HGF 1 FGF7 (Homo sapiens)

Pain Link Frequency Relevance Heat IPN 4 97.32 metalloproteinase 2 76.44 Pain 17 72.68 Opioid 2 60.00 Analgesic 3 59.44 Inflammation 21 48.80 pruritus 1 38.56 Hypoesthesia 1 36.40 Paresthesia 1 35.28 cytokine 7 31.04

Disease Link Frequency Relevance Heat Cancer 624 99.60 Injury 13 95.44 Colon Cancer 2 94.92 Adhesions 3 94.80 Salivary Gland Disease 7 87.68 Apoptosis 10 86.52 Solid Tumor 1 85.16 Mucositis 63 78.80 Prostate Cancer 53 73.32 Pain 17 72.68

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Likewise, the secretion of a protein detectable by a KGF-specific ELISA into the culture medium of fibroblasts and epithelial tumour cells was confirmed.

Localization (secretion) of KGF in fibroblasts associated with cancer

1) Confidence 0.80 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.54 Pain Relevance 0

Measurements were performed in triplicate, and experiments were repeated at least three times. b KGF-induced (0.2 ?

Localization (repeated) of KGF

2) Confidence 0.75 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.12 Pain Relevance 0

Primary antibodies were for KGF MAB2511 Clone 29568, dilution 1:250; for KGF receptor MAB665 Clone 98707, dilution 1:250 (both R&D Systems) and for actin IgG1, dilution 1:1,000 (Santa Cruz, Santa Cruz, USA).

Localization (for) of KGF receptor

3) Confidence 0.75 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.19 Pain Relevance 0

The secretion of KGF protein into the culture medium was tested for fibroblasts (DF-19), tumour cell cultures (BW-225, GR-145, OH-65, ZMK-1), and immortalized keratinocytes (HaCat) by ELISA.

Localization (secretion) of KGF protein in keratinocytes associated with cancer

4) Confidence 0.71 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.42 Pain Relevance 0

For confirmation, immortalized keratinocytes (HaCat cells) were tested and showed KGF mRNA expression and secretion as well.

Localization (secretion) of KGF mRNA in keratinocytes

5) Confidence 0.71 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.36 Pain Relevance 0

In summary, the delivered exogenous huKGF (i.e., released from a biomaterial matrix) operates in tandem with fibroblasts in regulating keratinocyte activation (i.e., IL-lbeta release and adhesion) in a surface-dependent manner.

Localization (released) of KGF in fibroblasts associated with adhesions

6) Confidence 0.68 Published 2005 Journal Biomaterials Section Abstract Doc Link 15621258 Disease Relevance 0.09 Pain Relevance 0.34

Consistent with this hypothesis, paracrine growth factors that are normally secreted by prostate stroma cells, such as epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) or interleukin 6 (IL6), are found to be overexpression in hormone-refractory cancer in association with a switch to autocrine production by cancer epithelial cells [16].

Localization (secreted) of KGF in HGF associated with cancer

7) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2957443 Disease Relevance 0.65 Pain Relevance 0

A truncated recombinant form of human KGF (?

Localization (form) of KGF

8) Confidence 0.65 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.26 Pain Relevance 0.07

In a phase I trial, Meropol determined that KGF was well tolerated at doses up to 40 ?

Localization (tolerated) of KGF

9) Confidence 0.62 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661654 Disease Relevance 1.09 Pain Relevance 0.16

Tumour cells are known to secrete growth factors other than KGF; however, two findings support the assumption that tumour-cell-derived KGF was causative for the observed stimulated proliferation of keratinocytes.

Localization (secrete) of KGF in keratinocytes associated with cancer

10) Confidence 0.62 Published 2010 Journal Radiat Environ Biophys Section Body Doc Link PMC2855434 Disease Relevance 0.41 Pain Relevance 0

General Comments

This test has worked.