Cancer Research,
Год журнала:
2023,
Номер
83(14), С. 2372 - 2386
Опубликована: Май 9, 2023
Hepatocellular
carcinoma
(HCC)
is
the
most
common
type
of
primary
liver
cancer
and
has
a
poor
prognosis.
Pituitary
tumor
transforming
gene
1
(PTTG1)
highly
expressed
in
HCC,
suggesting
it
could
play
an
important
role
hepatocellular
carcinogenesis.
Here,
we
evaluated
impact
PTTG1
deficiency
on
HCC
development
using
diethylnitrosamine
(DEN)-induced
mouse
model
hepatitis
B
virus
(HBV)
regulatory
X
protein
(HBx)-induced
spontaneous
model.
significantly
suppressed
DEN-
HBx-induced
Mechanistically,
promoted
asparagine
synthetase
(ASNS)
transcription
by
binding
to
its
promoter,
(Asn)
levels
were
correspondingly
increased.
The
elevated
Asn
subsequently
activated
mTOR
pathway
facilitate
progression.
In
addition,
asparaginase
treatment
reversed
proliferation
induced
overexpression.
Furthermore,
HBx
ASNS
metabolism
upregulating
expression.
Overall,
involved
reprogramming
promote
progression
may
serve
as
therapeutic
diagnostic
target
for
HCC.PTTG1
upregulated
increases
production
stimulate
activity
Experimental Hematology and Oncology,
Год журнала:
2024,
Номер
13(1)
Опубликована: Авг. 1, 2024
Abstract
Hepatocellular
carcinoma
(HCC)
is
a
highly
heterogeneous
malignancy
with
high
incidence,
recurrence,
and
metastasis
rates.
The
emergence
of
immunotherapy
has
improved
the
treatment
advanced
HCC,
but
problems
such
as
drug
resistance
immune-related
adverse
events
still
exist
in
clinical
practice.
immunosuppressive
tumor
microenvironment
(TME)
HCC
restricts
efficacy
essential
for
progression
metastasis.
Therefore,
it
necessary
to
elucidate
mechanisms
behind
TME
develop
apply
immunotherapy.
This
review
systematically
summarizes
pathogenesis
formation
TME,
by
which
accelerates
We
also
status
further
discuss
existing
challenges
potential
therapeutic
strategies
targeting
TME.
hope
inspire
optimizing
innovating
immunotherapeutic
comprehensively
understanding
structure
function
HCC.
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2021,
Номер
35(11)
Опубликована: Авг. 31, 2021
Abstract
Solid
cancers
comprise
a
large
number
of
new
cases
and
deaths
from
cancer
each
year
globally.
There
are
strategies
for
addressing
tumors
raised
solid
organs
including
surgery,
chemotherapy,
radiotherapy,
targeted
therapy,
immunotherapy,
combinational
stem
cell
extracellular
vesicle
(EV)
therapy.
Surgery,
chemotherapy
the
dominant
cures,
but
not
always
effective,
in
which
even
localized
tumor
there
is
possibility
relapse
after
surgical
resection.
Over
half
patients
will
receive
radiotherapy
as
part
their
therapeutic
schedule.
Radiotherapy
can
cause
an
abscopal
response
boosting
activity
immune
system
outside
local
field
radiation,
it
may
also
unwanted
bystander
effect,
predisposing
nonradiated
cells
into
carcinogenesis.
In
context
checkpoint
inhibition
known
standard‐of‐care,
major
concern
regard
with
cold
that
show
low
responses
to
such
Stem‐cell
therapy
be
used
send
prodrugs
toward
area;
this
strategy,
however,
has
its
own
predicaments,
attraction
other
sites
healthy
tissues
instability.
A
substitute
quite
novel
strategy
use
EVs,
by
virtue
stability
potential
cross
biological
barriers
long‐term
storage
contents.
Combination
current
focus.
Despite
advances
field,
still
unmet
concerns
area
effective
raising
challenges
opportunities
future
investigations.
Journal of Clinical Investigation,
Год журнала:
2021,
Номер
131(8)
Опубликована: Март 9, 2021
Although
cancer
cells
are
frequently
faced
with
a
nutrient-
and
oxygen-poor
microenvironment,
elevated
hexosamine-biosynthesis
pathway
(HBP)
activity
protein
O-GlcNAcylation
(a
nutrient
sensor)
contribute
to
rapid
growth
of
tumor
emerging
hallmarks
cancer.
Inhibiting
could
be
promising
anticancer
strategy.
The
gluconeogenic
enzyme
phosphoenolpyruvate
carboxykinase
1
(PCK1)
is
downregulated
in
hepatocellular
carcinoma
(HCC).
However,
little
known
about
the
potential
role
PCK1
enhanced
HBP
HCC
carcinogenesis
under
glucose-limited
conditions.
In
this
study,
knockout
markedly
global
levels
low-glucose
Mechanistically,
metabolic
reprogramming
PCK1-loss
hepatoma
led
oxaloacetate
accumulation
increased
de
novo
uridine
triphosphate
synthesis
contributing
diphosphate-N-acetylglucosamine
(UDP-GlcNAc)
biosynthesis.
Meanwhile,
deletion
also
resulted
AMPK-GFAT1
axis
inactivation,
promoting
UDP-GlcNAc
for
O-GlcNAcylation.
Notably,
lower
expression
promoted
CHK2
threonine
378
O-GlcNAcylation,
counteracting
its
stability
dimer
formation,
increasing
CHK2-dependent
Rb
phosphorylation
cell
proliferation.
Moreover,
aminooxyacetic
acid
hemihydrochloride
6-diazo-5-oxo-L-norleucine
blocked
HBP-mediated
suppressed
progression
liver-specific
Pck1-knockout
mice.
We
reveal
link
between
depletion
hyper-O-GlcNAcylation
that
underlies
oncogenesis
suggest
therapeutic
targets
act
by
inhibiting
Hepatology,
Год журнала:
2022,
Номер
76(4), С. 951 - 966
Опубликована: Янв. 25, 2022
Aberrant
activation
of
fatty
acid
synthase
(FASN)
is
a
major
metabolic
event
during
the
development
HCC.
We
evaluated
therapeutic
efficacy
TVB3664,
FASN
inhibitor,
either
alone
or
in
combination,
for
HCC
treatment.The
and
molecular
pathways
targeted
by
with
tyrosine
kinase
inhibitors
checkpoint
inhibitor
anti-programmed
death
ligand
1
antibody,
were
assessed
human
cell
lines
multiple
oncogene-driven
mouse
models.
RNA
sequencing
was
performed
to
elucidate
effects
TVB3664
on
global
gene
expression
tumor
metabolism.
significantly
ameliorated
liver
phenotype
aged
mice
AKT-induced
hepatic
steatosis.
monotherapy
showed
moderate
NASH-related
murine
HCCs,
induced
loss
phosphatase
tensin
homolog
MET
proto-oncogene,
receptor
(c-MET)
overexpression.
combination
cabozantinib,
triggered
regression
this
model
but
did
not
improve
responsiveness
immunotherapy.
Global
revealed
that
predominantly
modulated
processes,
whereas
synergized
cabozantinib
down-regulate
cancer-related
pathways,
especially
AKT/mammalian
target
rapamycin
pathway
proliferation
genes.
also
improved
sorafenib
FASN-dependent
c-MYC-driven
model.
However,
had
no
nor
synergistic
FASN-independent
models.This
preclinical
study
suggests
limited
targeting
as
treatment.
could
be
combined
other
drugs
effectiveness.
These
therapies
developed
based
driver
oncogenes,
supporting
precision
medicine
approaches
Cancer Communications,
Год журнала:
2022,
Номер
42(12), С. 1234 - 1256
Опубликована: Сен. 15, 2022
Abstract
Pancreatic
cancer
is
one
of
the
most
serious
health
issues
in
developed
and
developing
countries,
with
a
5‐year
overall
survival
rate
currently
<9%.
Patients
typically
present
advanced
disease
due
to
vague
symptoms
or
lack
screening
for
early
detection.
Surgical
resection
represents
only
chance
cure,
but
treatment
options
are
limited
diseases,
such
as
distant
metastatic
locally
progressive
tumors.
Although
adjuvant
chemotherapy
has
improved
long‐term
outcomes
patients,
its
response
low.
So,
exploring
other
new
treatments
urgent.
In
recent
years,
increasing
evidence
shown
that
lipid
metabolism
can
support
tumorigenesis
progression
well
resistance
through
enhanced
synthesis,
storage,
catabolism.
Therefore,
better
understanding
networks
may
provide
novel
promising
strategies
diagnosis,
prognosis
estimation,
targeted
therapy
pancreatic
patients.
this
review,
we
first
enumerate
discuss
current
knowledge
about
advances
made
regulation
cancer.
addition,
summarize
preclinical
studies
clinical
trials
drugs
targeting
metabolic
systems
Finally,
highlight
challenges
opportunities
pathways
precision
therapies
EBioMedicine,
Год журнала:
2021,
Номер
73, С. 103661 - 103661
Опубликована: Окт. 28, 2021
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
affecting
more
people
globally.
Indeed,
NAFLD
a
spectrum
of
metabolic
dysfunctions
that
can
progress
to
hepatocellular
carcinoma
(NAFLD-HCC).
This
development
occur
in
non-cirrhotic
and
thus,
often
lack
clinical
surveillance.
The
aim
this
study
was
develop
non-invasive
surveillance
method
for
NAFLD-HCC.
