INT68133

Context Info Confidence 0.81 First Reported 1997 Last Reported 2011 Negated 2 Speculated 2 Reported most in Body Documents 36 Total Number 38 Disease Relevance 15.37 Pain Relevance 9.14

signal transduction (Fgf2) extracellular space (Fgf2) extracellular region (Fgf2) nucleus (Fgf2) embryo development (Fgf2) cytoplasm (Fgf2)

Anatomy Link Frequency fibroblast 9 neuronal 2 blood 2 nerve 2 MSCs 2 Fgf2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat cytokine 241 100.00 bradykinin 18 100.00 qutenza 8 100.00 Glutamate 43 99.98 Nerve growth factor 227 99.88 metalloproteinase 118 99.80 Inflammation 170 99.60 Endep 3 99.06 dorsal root ganglion 2 99.00 COX-2 inhibitor 23 98.60

Disease Link Frequency Relevance Heat Cancer 74 100.00 Adhesions 65 100.00 Necrosis 29 100.00 INFLAMMATION 192 99.60 Diabetes Mellitus 851 99.20 Disease 64 99.12 Ganglion Cysts 7 98.52 Pain 20 98.28 Nervous System Injury 14 98.04 Injury 204 97.96

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The cytoplasmatic and nuclear localization of the FGF-2 immunoreactivity [9] were taken into account in the discrimination of the neuronal and glial FGF-2 cell profiles.

Localization (localization) of FGF-2 in neuronal

1) Confidence 0.81 Published 2010 Journal J Brachial Plex Peripher Nerve Inj Section Body Doc Link PMC2995486 Disease Relevance 0.09 Pain Relevance 0

It was reported that the FGF-2 synthesized in the tongue may be retrogradaly transported to the hypoglossal nucleus thus acting as a target derived neurotrophic factor.

Localization (transported) of FGF-2 in nucleus

2) Confidence 0.75 Published 2010 Journal J Brachial Plex Peripher Nerve Inj Section Body Doc Link PMC2995486 Disease Relevance 0.06 Pain Relevance 0.10

Furthermore, a higher amount of FGF-2 was found in the nucleus of the reactive astrocytes of axotomized facial nuclei (Figure 4).

Localization (found) of FGF-2 in astrocytes

3) Confidence 0.75 Published 2010 Journal J Brachial Plex Peripher Nerve Inj Section Body Doc Link PMC2995486 Disease Relevance 0.07 Pain Relevance 0

Observations such as reduced b-FGF and VEGF secretion and MMP-9 regulation reveals that COX-2 inhibitors possess the potential to be exploited in the in vivo model to better understand their benefits as an adjuvant to the currently available chemotherapy for KS.

Localization (secretion) of b-FGF associated with sarcoma, metalloproteinase and cox-2 inhibitor

4) Confidence 0.73 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2820536 Disease Relevance 0.98 Pain Relevance 0.33

The cytoplasmatic and nuclear localization of the FGF-2 immunoreactivity [9] were taken into account in the discrimination of the neuronal and glial FGF-2 cell profiles.

Localization (localization) of FGF-2 in neuronal

5) Confidence 0.71 Published 2010 Journal J Brachial Plex Peripher Nerve Inj Section Body Doc Link PMC2995486 Disease Relevance 0.09 Pain Relevance 0

Immunohistochemically, red-colored cells indicating PKH26-positive MSCs were surrounded by a green color suggesting local secretion of bFGF and VEGF from the MSCs (Fig. 3A and B).

Localization (secretion) of bFGF

6) Confidence 0.68 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.47 Pain Relevance 0.21

MSCs have recently been shown to differentiate into multilineage cell types (8,9) and to secrete various cytokines, including bFGF and VEGF (10–13).

Localization (secrete) of bFGF in MSCs associated with cytokine

7) Confidence 0.68 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.79 Pain Relevance 0.30

In our study, bFGF and VEGF mRNA expressions in STZ-induced diabetic rats were upregulated in MSC-injected hind limb muscles, and MSCs maintained their viabilities and abilities to secrete bFGF and VEGF even 4 weeks after the transplantation.

Localization (secrete) of bFGF in limb muscles associated with diabetes mellitus

8) Confidence 0.68 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.32 Pain Relevance 0.16

The level of therapeutic vasculogenesis induced by MSC transplantation was similar to that by endothelial progenitor cell transplantation, as we previously reported (16), and the differentiation or incorporation of MSCs to vessels was not observed, suggesting that neovasculalization induced by transplantation would be mediated through the actions of angiogenic factors such as VEGF and bFGF secreted from MSCs, which would explain the improvement of NBF.

Localization (secreted) of bFGF in vessels

9) Confidence 0.68 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.35 Pain Relevance 0.07

Therefore, VEGF and bFGF secreted by the transplanted MSCs would additively exert angiogenic and neurotrophic actions.

Localization (secreted) of bFGF

10) Confidence 0.68 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.42 Pain Relevance 0.13

We used immunohistochemistry to examine spinal localization of the cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-beta1 (TGF-beta) at 3, 14, and 35 days following sciatic cryoneurolysis or 6 days following chronic constriction injury as compared with normal, unoperated rats.

Spec (examine) Localization (localization) of bFGF in fibroblast associated with necrosis, cancer, eae, injury and cytokine

11) Confidence 0.65 Published 1997 Journal Brain Res. Section Abstract Doc Link 9219862 Disease Relevance 1.03 Pain Relevance 0.69

We used immunohistochemistry to examine spinal localization of the cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-beta1 (TGF-beta) at 3, 14, and 35 days following sciatic cryoneurolysis or 6 days following chronic constriction injury as compared with normal, unoperated rats.

Spec (examine) Localization (localization) of basic fibroblast growth factor in fibroblast associated with necrosis, cancer, eae, injury and cytokine

12) Confidence 0.65 Published 1997 Journal Brain Res. Section Abstract Doc Link 9219862 Disease Relevance 1.03 Pain Relevance 0.69

Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed.

Localization (colocalization) of bFGF in MSCs

13) Confidence 0.64 Published 2008 Journal Diabetes Section Abstract Doc Link PMC2570407 Disease Relevance 0.65 Pain Relevance 0.24

Scaffolds were characterized in vitro respect to their morphology, VEGF and bFGF release kinetics and bioactivity.

Localization (release) of bFGF

14) Confidence 0.62 Published 2010 Journal Biomaterials Section Abstract Doc Link 20381861 Disease Relevance 0.08 Pain Relevance 0.16

Of particular interest for future studies are those proteins that are not normalized (Fgf2 and Crybb2) or only partially normalized (Cp, Cryba3, Lgals3, Stat3) by insulin treatment, as these persistent changes reflect the limitations of insulin to restore the retina to a nondiabetic state.

Neg (not) Localization (normalized) of Fgf2 in retina

15) Confidence 0.61 Published 2011 Journal PLoS ONE Section Body Doc Link PMC3020973 Disease Relevance 0.17 Pain Relevance 0

It can be speculated that diabetic conditions such as hyperglycemia and impaired local microcirculation might cause or require the transplanted MSCs to more strongly produce and secrete bFGF and VEGF.

Localization (secrete) of bFGF associated with hyperglycemia and diabetes mellitus

16) Confidence 0.60 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.65 Pain Relevance 0.11

Four weeks after the transplantation, MSCs maintained their viabilities and secreted angiogenic factors such as VEGF and bFGF at the injected sites.

Localization (secreted) of bFGF

17) Confidence 0.60 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.39 Pain Relevance 0.09

Local production and secretion of bFGF and VEGF.

Localization (secretion) of bFGF

18) Confidence 0.60 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.49 Pain Relevance 0.10

On the other hand, MSCs have been reported to secrete a wide array of cytokines, such as bFGF, VEGF, monocyte chemoattractant protein-1, and stem cell–derived factor-1 (12).

Localization (secrete) of bFGF in monocyte associated with cytokine

19) Confidence 0.60 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.27 Pain Relevance 0.14

In fact, MSC transplantation has been performed in the field of ischemic diseases, and it has been suggested that its plausible effects would be mediated largely through paracrine actions of locally released arteriogenic cytokines, including bFGF and VEGF (11,13,30).

Localization (released) of bFGF associated with disease and cytokine

20) Confidence 0.60 Published 2008 Journal Diabetes Section Body Doc Link PMC2570407 Disease Relevance 0.28 Pain Relevance 0.12

General Comments

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