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EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma.
[liposarcoma]
Soft
tissue
sarcomas
(
STS
)
are
heterogeneous
malignant
tumors
of
mesenchymal
origin
.
Due
to
low
incidence
and
high
number
of
different
histological
subtypes
,
their
pathogenesis
and
thus
potential
targets
for
their
therapy
remain
barely
investigated
.
Several
studies
revealed
significant
higher
EPHB
4
expression
in
malignancies
such
as
prostate
and
colorectal
cancer
showing
survival
advantages
for
these
tumor
cells
.
Therefore
we
studied
the
expression
of
EPHB
4
in
a
total
of
46
clinical
human
specimens
of
different
STS
and
human
fibroblasts
.
EPHB
4
mRNA
and
protein
expression
were
significantly
increased
in
synovial
sarcoma
.
After
targeting
EPHB
4
in
fibrosarcoma
,
synovial
sarcoma
,
liposarcoma
and
MFH
sarcoma
cell
lines
by
siRNA
or
by
inhibition
of
autophosphorylation
using
the
specific
EPHB
4
kinase
inhibitor
NVP-BHG
712
a
decreased
proliferation
rate
/
vitality
of
synovial-
and
fibrosarcoma
cells
was
observed
.
Silencing
of
EPHB
4
significantly
reduced
the
transmigration
of
synovial
sarcoma
cells
towards
fibroblasts
and
endothelial
cells
.
In
addition
,
we
assessed
the
anti-metastatic
effect
of
EPHB
4
inhibition
in
vivo
by
intraperitoneal
administration
of
the
EPHB
4
inhibitor
in
an
appropriate
sarcoma
lung
metastasis
xenograft
model
.
As
result
43
%
of
NVP-BHG
712
treated
mice
(
n
=
3
/
7
)
developed
pulmonary
metastases
whereas
all
control
mice
(
n
=
5
)
revealed
lung
metastases
.
The
residual
57
%
of
mice
(
n
=
4
/
7
)
showed
only
small
local
tumor
cell
spots
.
Size
measurements
of
the
Vimentin
positive
area
explained
significant
decrease
in
lung
metastasis
formation
(
p
<
0
.
05
)
after
EPHB
4
kinase
inhibition
.
In
summary
,
these
data
provide
first
evidence
of
the
importance
of
EPHB
4
in
the
tumorigenesis
of
synovial
sarcoma
and
present
EPHB
4
as
a
potential
target
in
the
therapy
of
this
malignancy
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated