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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
"combined immunodeficiency xenograft model"
symptom
severe combined immunodeficiency
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