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CREB-induced inflammation is important for malignant mesothelioma growth.
[severe combined immunodeficiency]
Malignant
mesothelioma
(
MM
)
is
an
aggressive
tumor
with
no
treatment
regimen
.
Previously
we
have
demonstrated
that
cyclic
AMP
response
element
binding
protein
(
CREB
)
is
constitutively
activated
in
MM
tumor
cells
and
tissues
and
plays
an
important
role
in
MM
pathogenesis
.
To
understand
the
role
of
CREB
in
MM
tumor
growth
,
we
generated
CREB-inhibited
MM
cell
lines
and
performed
in
Â
vitro
and
in
Â
vivo
experiments
.
In
Â
vitro
experiments
demonstrated
that
CREB
inhibition
results
in
significant
attenuation
of
proliferation
and
drug
resistance
of
MM
cells
.
CREB-silenced
MM
cells
were
then
injected
into
severe
combined
immunodeficiency
mice
,
and
tumor
growth
in
s
.
c
.
and
i
.
p
.
models
of
MM
was
followed
.
We
observed
significant
inhibition
in
MM
tumor
growth
in
both
s
.
c
.
and
i
.
p
.
models
and
the
presence
of
a
chemotherapeutic
drug
,
doxorubicin
,
further
inhibited
MM
tumor
growth
in
the
i
.
p
.
model
.
Peritoneal
lavage
fluids
from
CREB-inhibited
tumor
-bearing
mice
showed
a
significantly
reduced
total
cell
number
,
differential
cell
counts
,
and
pro-
inflammatory
cytokines
and
chemokines
(
IL
-
6
,
IL
-
8
,
regulated
on
activation
normal
T
cell
expressed
and
secreted
,
monocyte
chemotactic
protein-
1
,
and
vascular
endothelial
growth
factor
)
.
In
Â
vitro
studies
showed
that
asbestos-induced
inflammasome
/
inflammation
activation
in
mesothelial
cells
was
CREB
dependent
,
further
supporting
the
role
of
CREB
in
inflammation
-induced
MM
pathogenesis
.
In
conclusion
,
our
data
demonstrate
the
involvement
of
CREB
in
the
regulation
of
MM
pathogenesis
by
regulation
of
inflammation
.
Diseases
Validation
Diseases presenting
"growth factor"
symptom
22q11.2 deletion syndrome
achondroplasia
adrenal incidentaloma
aniridia
cadasil
cholangiocarcinoma
coats disease
dedifferentiated liposarcoma
dentin dysplasia
dentinogenesis imperfecta
dystrophic epidermolysis bullosa
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
holt-oram syndrome
inclusion body myositis
kallmann syndrome
krabbe disease
liposarcoma
lymphangioleiomyomatosis
oculocutaneous albinism
oral submucous fibrosis
pleomorphic liposarcoma
primary effusion lymphoma
primary hyperoxaluria type 1
severe combined immunodeficiency
systemic capillary leak syndrome
von hippel-lindau disease
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
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