INT197105

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Context Info
Confidence 0.42
First Reported 2006
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 13
Total Number 14
Disease Relevance 11.48
Pain Relevance 0.92

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular region (FLT4) plasma membrane (FLT4) nucleus (FLT4)
cytoplasm (FLT4)
Anatomy Link Frequency
lymphatic vessels 6
plasma 2
cortical bone 1
FLT4 (Homo sapiens)
Pain Link Frequency Relevance Heat
cytokine 111 99.04 Very High Very High Very High
nud 2 82.00 Quite High
Pain 24 72.56 Quite High
Inflammation 30 70.32 Quite High
abdominal pain 2 68.16 Quite High
headache 14 66.88 Quite High
Potency 2 60.88 Quite High
Central nervous system 2 60.40 Quite High
cva 5 58.56 Quite High
Osteoarthritis 2 40.24 Quite Low
Disease Link Frequency Relevance Heat
Helminth Infection 410 99.68 Very High Very High Very High
Camurati-engelmann Disease 12 98.88 Very High Very High Very High
Lymphedema 560 97.44 Very High Very High Very High
Cancer 290 95.56 Very High Very High Very High
Ovarian Cancer 204 95.52 Very High Very High Very High
Infection 126 95.24 Very High Very High Very High
Lymphatic Filariasis 188 95.20 Very High Very High Very High
Disease 180 94.52 High High
Thyroid Disease 4 94.20 High High
Death 37 93.72 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Importantly, the reduction of the VEGF-C/sVEGFR-3 preceded the amelioration of the dilated lymphatic vessels and LE.
Negative_regulation (reduction) of VEGFR-3 in lymphatic vessels associated with lymphedema
1) Confidence 0.42 Published 2009 Journal Parasite Immunology Section Body Doc Link PMC2784903 Disease Relevance 0.75 Pain Relevance 0
Doxycycline treatment not only reduced Wolbachia copy numbers by 95% in W. bancrofti-infected patients but also reduced the plasma levels of VEGF-C/sVEGFR-3, resulting in amelioration of dilated lymphatic vessels and improvement in the conditions of LE patients.
Negative_regulation (reduced) of VEGFR-3 in lymphatic vessels associated with lymphedema
2) Confidence 0.42 Published 2009 Journal Parasite Immunology Section Body Doc Link PMC2784903 Disease Relevance 0.80 Pain Relevance 0.16
Targeting the filarial worms by doxycycline reduces the levels of VEGF-C/sVEGFR-3, with amelioration of dilated supratesticular lymphatic vessels and improvement in the conditions of lymphedema patients (Table 2, Figure 2).
Negative_regulation (reduces) of sVEGFR-3 in lymphatic vessels associated with helminth infection and lymphedema
3) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1564427 Disease Relevance 0.37 Pain Relevance 0
We report that 6 wk of doxycycline had a strong macrofilaricidal activity; and targeting the endosymbiotic Wolbachia in filarial worms resulted in the reduction of plasma levels of VEGF-C/sVEGFR-3, which were associated with amelioration of dilated supratesticular lymphatic vessels and improvement of lymphedema in lymphatic filariasis patients.


Negative_regulation (reduction) of sVEGFR-3 in plasma associated with helminth infection, lymphatic filariasis and lymphedema
4) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1564427 Disease Relevance 1.03 Pain Relevance 0.03
It is therefore conceivable that any therapeutic intervention that causes reduction of VEGF-C–inducing proinflammatory cytokines such as TNF, IL-1B [45], etc. would be able to reduce levels of VEGF-C/sVEGFR-3, and hence lead to reduction of dilated supratesticular lymphatic vessels as we have shown here.
Negative_regulation (reduce) of sVEGFR-3 in lymphatic vessels associated with cytokine
5) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1564427 Disease Relevance 0.62 Pain Relevance 0.17
The mechanism of action of doxycycline on the reduction of VEGF-C/sVEGFR-3 and its ameliorating effect on lymphatic vessel is not yet fully clarified.
Negative_regulation (reduction) of sVEGFR-3 in lymphatic vessel
6) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1564427 Disease Relevance 0.73 Pain Relevance 0.10
In conclusion, a 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.


Negative_regulation (reduction) of sVEGFR-3 in lymphatic vessels associated with lymphatic filariasis
7) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Abstract Doc Link PMC1564427 Disease Relevance 1.04 Pain Relevance 0
Mean plasma values of sVEGFR-3 in the doxycycline group were also significantly reduced 12 mo after doxycycline treatment to a level close to that of the endemic normals (p = 0.0125, Figure 6).
Negative_regulation (reduced) of sVEGFR-3 in plasma
8) Confidence 0.35 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1564427 Disease Relevance 0.47 Pain Relevance 0
Vandetanib (ZD-6474) is a TK inhibitor of VEGFRR-2, VEGFR-3, Ret and EGFR (Ciardiello et al 2003) thus inhibiting both the VEGF dependent angiogenesis and EGFR dependent tumor cell proliferation.
Negative_regulation (inhibitor) of VEGFR-3 associated with cancer
9) Confidence 0.25 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727890 Disease Relevance 0.42 Pain Relevance 0.03
Vatalanib is a pan-VEGFR tyrosine kinase inhibitor with activity against VEGFR-1, VEGFR-2 and VEGFR-3.
Negative_regulation (inhibitor) of VEGFR-3
10) Confidence 0.24 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727890 Disease Relevance 0.63 Pain Relevance 0.03
VEGFR Tyrosine Kinase Inhibitors

Cediranib (AZD2171, CED) is a highly selective and potent oral tyrosine kinase inhibitor (TKI) of VEGFR1, VEGFR2, VEGFR3, and c-Kit.

Negative_regulation (inhibitor) of VEGFR3 associated with camurati-engelmann disease
11) Confidence 0.09 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2804796 Disease Relevance 2.18 Pain Relevance 0.33
The molecule also inhibits other tyrosine kinase receptors including VEGFR1, VEGFR2, VEGFR3, PDGFRB, flt-3, and c-kit.
Negative_regulation (inhibits) of VEGFR3
12) Confidence 0.09 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2804796 Disease Relevance 1.53 Pain Relevance 0.04
Cediranib (AZD2171) is an orally available selective inhibitor of VEGFR 1, 2, 3, PDGFR, c-kit, and FLT-4.
Negative_regulation (inhibitor) of FLT-4
13) Confidence 0.09 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2527326 Disease Relevance 0.91 Pain Relevance 0.03
The cortical bone of the scapula of the dog was removed which was the same size of PCL-TCP block (Osteopore International Pte, Singapore; 5.0×5.0×8.0 mm in size), and the following graft material then was fixed with orthodontic mini-implant, Dual-top® (Titanium alloy, Jeil Co.
Negative_regulation (block) of PCL-TCP in cortical bone
14) Confidence 0.02 Published 2009 Journal Yonsei Medical Journal Section Abstract Doc Link PMC2796411 Disease Relevance 0 Pain Relevance 0

General Comments

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