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Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma.
[esophageal squamous cell carcinoma]
The
insulin
-like
growth
factor
type
1
receptor
(
IGF-
1
R
)
plays
an
essential
role
in
the
development
of
numerous
cancers
.
Figitumumab
(
CP
)
is
not
only
a
monocloncal
antibody
,
it
also
has
agonist
activity
on
IGF-
1
R
.
The
antitumor
activity
of
CP
in
esophageal
squamous
cell
carcinoma
(
ESCC
)
is
still
unclear
.
In
our
study
,
we
identified
IGF-
1
R
as
an
independent
prognostic
factor
in
ESCC
patients
,
and
investigated
the
antitumor
effects
of
CP
in
ESCC
cell
lines
.
CP
suppressed
tumor
growth
and
sensitized
cells
to
chemotherapeutic
drugs
.
In
addition
,
CP
inhibited
cell
proliferation
,
migration
,
colony
forming
activity
and
anti-apoptosis
induced
by
IGF-
1
.
Our
results
showed
that
CP
not
only
inhibited
IGF-
1
induced
receptor
autophosphorylation
and
downstream
signaling
,
but
also
triggered
β-arrestin
1
and
G
protein-coupled
receptor
kinases
(
GRKs
)
mediated
ERK
1
/
2
activation
,
indicating
CP
as
a
biased
agonist
for
IGF-
1
R
.
Inhibition
of
ERK
1
/
2
enhanced
the
antitumor
activity
of
CP
.
Furthermore
,
CP
was
a
more
powerful
agonist
for
IGF-
1
R
down-regulation
than
IGF-
1
,
and
dysregulation
of
β-arrestin
1
and
GRKs
affected
this
down-regulation
.
Thus
,
we
demonstrated
antitumor
activities
of
CP
on
ESCC
,
and
as
a
biased
agonist
,
CP
induced
ERK
1
/
2
activation
and
receptor
down-regulation
required
β-arrestin
1
and
GRKs
,
suggesting
a
promising
role
for
targeting
IGF-
1
R
in
ESCC
.
Diseases
Validation
Diseases presenting
"downstream signaling"
symptom
esophageal carcinoma
esophageal squamous cell carcinoma
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