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Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma.
[severe combined immunodeficiency]
Autophagy
has
an
important
role
in
tumor
biology
of
hepatocellular
carcinoma
(
HCC
)
.
Recent
studies
demonstrated
that
tissue
factor
(
TF
)
combined
with
coagulation
factor
VII
(
FVII
)
has
a
pathological
role
by
activating
a
G-
protein-coupled
receptor
called
protease-activated
receptor
2
(
PAR
2
)
for
tumor
growth
.
The
present
study
aimed
to
investigate
the
interactions
of
autophagy
and
the
coagulation
cascade
in
HCC
.
Seventy
HCC
patients
who
underwent
curative
liver
resection
were
recruited
.
Immunohistochemical
staining
and
western
blotting
were
performed
to
determine
TF
,
FVII
,
PAR
2
and
light
chain
3
(
LC
3
A
/
B
)
expressions
in
tumors
and
their
contiguous
normal
regions
.
We
found
that
the
levels
of
autophagic
marker
LC
3
A
/
B-
II
and
coagulation
proteins
(
TF
,
FVII
and
PAR
2
)
were
inversely
correlated
in
human
HCC
tissues
.
Treatments
with
TF
,
FVII
or
PAR
2
agonist
downregulated
LC
3
A
/
B-
II
with
an
increased
level
of
mTOR
in
Hep
3
B
cells
;
in
contrast
,
knockdown
of
TF
,
FVII
or
PAR
2
increased
LC
3
A
/
B
.
Furthermore
,
mTOR
silencing
restored
the
impaired
expression
of
LC
3
A
/
B-
II
in
TF
-
,
FVII-
or
PAR
2
-
treated
Hep
3
B
cells
and
activated
autophagy
.
Last
,
as
an
in
vivo
correlate
,
we
administered
TF
,
FVII
or
PAR
2
agonist
in
a
NOD
/
severe
combined
immunodeficiency
xenograft
model
and
showed
decreased
LC
3
A
/
B
protein
levels
in
HepG
2
tumors
with
treatments
.
Overall
,
our
present
study
demonstrated
that
TF
,
FVII
and
PAR
2
regulated
autophagy
mainly
via
mTOR
signaling
.
The
interaction
of
coagulation
and
autophagic
pathways
may
provide
potential
targets
for
further
therapeutic
application
in
HCC
.
Diseases
Validation
Diseases presenting
"tumor growth"
symptom
adrenal incidentaloma
carcinoma of the gallbladder
cholangiocarcinoma
cowden syndrome
cystinuria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
liposarcoma
lymphangioleiomyomatosis
primary effusion lymphoma
severe combined immunodeficiency
von hippel-lindau disease
waldenström macroglobulinemia
wiskott-aldrich syndrome
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