Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Апрель 6, 2025
Abstract
Protein
tyrosine
phosphatase
mitochondrial
1
(PTPMT1),
is
a
member
of
the
protein
superfamily
localized
on
inner
membrane,
and
regulates
biosynthesis
cardiolipin.
Given
important
position
PTPMT1
in
function
metabolism,
pharmacological
targeting
considered
promising
manner
disease
treatments.
In
this
study,
we
mainly
investigated
role
hepatocellular
carcinoma
(HCC)
ferroptosis,
new
type
cell
death
accompanied
by
significant
iron
accumulation
lipid
peroxidation.
Herein,
inhibition
was
induced
alexidine
dihydrochloride
(AD,
dibiguanide
compound).
Human
HCC
lines
with
knockout
overexpression
were
established
using
CRISPR/Cas9
lentiviral
transduction
methods,
respectively.
The
regulating
ferroptosis
evaluated
vitro
vivo.
Our
results
indicated
that
PTPMT1,
facilitated
AD
treatment,
heightens
susceptibility
to
cystine
deprivation-ferroptosis,
treatment
promoted
conversion
from
ferritin-bound
Fe
3+
free
2+
,
which
contributed
labile
pool
cytoplasm.
Meanwhile,
also
formation
both
swollen
mitochondria
donut
mitochondria,
enhanced
metabolism
process
form
succinate
fumarate
tricarboxylic
acid
(TCA)
cycle,
increased
sensitivity
cells
deprivation-induced
ferroptosis.
total,
our
work
reveals
close
association
cysteine
providing
novel
insight
into
chemotherapy
strategies
against
human
HCC.
Hepatology Communications,
Год журнала:
2024,
Номер
8(5)
Опубликована: Апрель 12, 2024
Alpha-fetoprotein
(AFP)
is
a
glycoprotein
that
plays
an
important
role
in
immune
regulation
with
critical
involvement
early
human
development
and
maintaining
the
balance
during
pregnancy.
Postfetal
development,
regulatory
mechanisms
controlling
AFP
undergo
shift
gene
transcription
suppressed.
Instead,
these
enhancers
refocus
their
activity
to
maintain
albumin
throughout
adulthood.
During
postnatal
period,
expression
can
increase
setting
of
hepatocyte
injury,
regeneration,
malignant
transformation.
It
first
oncoprotein
discovered
routinely
used
as
part
screening
strategy
for
HCC.
has
been
shown
be
powerful
prognostic
biomarker,
multiple
HCC
prognosis
models
confirmed
independent
utility
AFP.
also
useful
predictive
biomarker
monitoring
treatment
response
In
addition
its
roles
modulation
promote
tumorigenesis
thus
investigated
therapeutic
target
this
review
article,
we
aim
provide
overview
AFP,
encompassing
discovery,
biological
role,
combination
other
biomarkers
how
it
impacts
clinical
practice
future
direction.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
Abstract
Gaudichaudione
H
(GH)
is
a
naturally
occurring
small
molecular
compound
derived
from
Garcinia
oligantha
Merr
.
(Clusiaceae),
but
the
full
pharmacological
functions
remain
unclear.
Herein,
potential
of
GH
in
disulfidptosis
regulation,
novel
form
programmed
cell
death
induced
by
disulfide
stress
explored.
The
omics
results
indicated
that
NRF2
signaling
could
be
significantly
activated
GH.
targets
are
associated
with
hepatocarcinogenesis
and
death.
Moreover,
both
glutathione
(GSH)
metabolism
NADP
+
‐NADPH
affected
GH,
indicating
regulation.
It
also
observed
enhanced
sensitivity
hepatocellular
carcinoma
(HCC)
cells
to
disulfidptosis,
which
dependent
on
activation
NRF2‐SLC7A11
pathway.
increased
levels
promoted
transcription
target
gene,
SLC7A11,
through
autophagy‐mediated
non‐canonical
mechanism.
Under
condition
glucose
starvation,
GH‐induced
upregulation
SLC7A11
aggravated
uptake
cysteine,
disturbance
GSH
synthesis,
depletion
NADPH,
accumulation
molecules,
ultimately
leading
formation
bonds
between
different
cytoskeleton
proteins
eventually.
Collectively,
findings
underscore
role
promoting
cancer
thereby
offering
promising
avenue
for
treatment
drug‐resistant
HCC
clinical
settings.
Liver
cancer,
primarily
HCC,
exhibits
highly
heterogeneous
histological
and
molecular
aberrations
across
tumors
within
individual
tumor
nodules.
Such
intertumor
intratumor
heterogeneities
may
lead
to
diversity
in
the
natural
history
of
disease
progression
various
clinical
disparities
patients.
Recently
developed
multimodality,
single-cell,
spatial
omics
profiling
technologies
have
enabled
interrogation
intertumor/intratumor
heterogeneity
cancer
cells
immune
microenvironment.
These
features
influence
efficacy
emerging
therapies
targeting
novel
pathways,
some
which
had
been
deemed
undruggable.
Thus,
comprehensive
characterization
at
levels
facilitate
discovery
biomarkers
that
enable
personalized
rational
treatment
decisions,
optimize
while
minimizing
risk
adverse
effects.
companion
will
also
refine
HCC
algorithms
stages
for
cost-effective
patient
management
by
optimizing
allocation
limited
medical
resources.
Despite
this
promise,
complexity
ever-expanding
inventory
therapeutic
agents
regimens
made
evaluation
translation
increasingly
challenging.
To
address
issue,
trial
designs
proposed
incorporated
into
recent
studies.
In
review,
we
discuss
latest
findings
landscape
their
potential
utility
as
biomarkers,
framework
application
predictive/prognostic
ongoing
biomarker-guided
trials.
new
developments
revolutionize
care
substantially
impact
still
dismal
mortality.
Current Opinion in Virology,
Год журнала:
2024,
Номер
67, С. 101423 - 101423
Опубликована: Июнь 25, 2024
Chronic
hepatitis
C
virus
(HCV)
infection
is
a
major
cause
of
hepatic
fibrosis
and
cirrhosis,
with
risk
for
the
development
hepatocellular
carcinoma
(HCC).
Although
highly
effective
direct-acting
antivirals
(DAAs)
are
available,
incidence,
morbidity,
mortality
HCV-associated
HCC
still
high.
This
article
reviews
current
knowledge
mechanisms
HCV-induced
carcinogenesis
special
focus
on
those
processes
that
continue
after
clearance
outlines
implications
patient
surveillance
DAA
treatment.
Clinical and Molecular Hepatology,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 26, 2024
Hepatocellular
carcinoma
(HCC)
is
a
major
global
burden,
ranking
as
the
third
leading
cause
of
cancer-related
mortality.HCC
due
to
chronic
hepatitis
B
virus
(HBV)
or
C
(HCV)
infection
has
decreased
universal
vaccination
for
HBV
and
effective
antiviral
therapy
both
HCV,
but
HCC
related
metabolic
dysfunction
associated
steatotic
liver
disease
(MASLD)
alcohol-associated
(ALD)
increasing.Biannual
ultrasonography
serum
α-fetoprotein
are
primary
surveillance
tools
early
detection
among
high-risk
patients
(e.g.,
cirrhosis,
HBV).Alternative
such
blood-based
biomarker
panels
abbreviated
MRIs
being
investigated.Multiphasic
CT
MRI
standard
diagnosis,
histological
confirmation
should
be
considered,
especially
when
inconclusive
findings
seen
on
cross-sectional
imaging.Staging
treatment
decisions
complex
made
in
multidisciplinary
settings,
incorporating
multiple
factors
including
tumor
degree
dysfunction,
patient
performance
status,
available
expertise,
preferences.Early-stage
best
treated
with
curative
options
resection,
ablation,
transplantation.For
intermediatestage
disease,
locoregional
therapies
primarily
recommended
although
systemic
may
preferred
large
intrahepatic
burden.In
advanced-stage
immune
checkpoint
inhibitor
(ICI)-based
regimen.In
this
review
article,
we
discuss
recent
epidemiology,
risk
factors,
care
continuum
encompassing
surveillance,
staging,
treatments.
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
prevalent
cancers,
characterized
by
high
morbidity
and
mortality
rates.
Recently,
immunotherapy
has
emerged
as
a
crucial
treatment
modality
for
HCC,
following
surgery,
locoregional
therapies,
targeted
therapies.
This
approach
harnesses
body's
immune
system
to
target
eliminate
cancer
cells,
potentially
resulting
in
durable
antitumor
responses.
However,
acquired
resistance
tumor
immunosuppressive
microenvironment
(TIME)
significantly
hinder
its
clinical
application.
advancements
nanotechnology,
coupled
with
deeper
understanding
biology
nano-biological
interactions,
have
led
development
various
nanoparticles
aimed
at
enhancing
therapeutic
efficacy
through
specific
targeting
tissues.
These
increase
accumulation
immunotherapeutic
drugs
within
microenvironment,
thereby
transforming
TIME.
In
this
review,
we
provide
concise
overview
fundamental
principles
governing
TIME
landscape
HCC
discuss
rationale
applications
context.
Additionally,
highlight
existing
challenges
potential
opportunities
translation
nanomedicines.
