American Journal of Translational Research,
Journal Year:
2024,
Volume and Issue:
16(12), P. 7317 - 7329
Published: Jan. 1, 2024
This
study
investigates
the
mechanism
underlying
sorafenib
resistance
in
hepatocellular
carcinoma
cells
(HCC),
focusing
on
DNA
damage
repair
(DDR)
pathways
to
develop
targeted
therapeutic
strategies.
Bioinformatics
analysis
was
used
screen
genes
associated
with
resistance,
which
further
demonstrated
by
western
blotting.
Cell
proliferation
determined
using
EdU
assay.
The
presence
of
binding
sites
between
valproic
acid
(VPA)
and
NOTCH1
analyzed
molecular
docking.
Comet
flow
cytometry
assays
evaluated
cell
cycle
arrest
induced
VPA
sorafenib-resistant
cells,
mechanistic
insights
gained
via
blotting
co-immunoprecipitation
(Co-IP).
We
found
that
NOTCH1/ATM
axis
plays
a
vital
role
prognosis
patients
liver
cancer
behavior
cells.
HCC
resistant
exhibited
enhanced
ability.
Moreover,
overexpression
sorafenib-sensitive
significantly
increased
proliferation.
Conversely,
silencing
expression
lines
reduced
their
proliferative
activity.
Additionally,
efficacy
against
sorafenib-resistance
modulating
NOTCH1/ATM/p-BRCA1/p-CHK2/γ-H2AX
signaling
homologous
recombination
(HR)
Targeting
ATM
is
promising
strategy
overcome
HCC,
particularly
through
combined
use
sorafenib.
International Journal of Nanomedicine,
Journal Year:
2024,
Volume and Issue:
Volume 19, P. 5581 - 5603
Published: June 1, 2024
Lenvatinib
(LVN)
is
a
potentially
effective
multiple-targeted
receptor
tyrosine
kinase
inhibitor
approved
for
treating
hepatocellular
carcinoma,
metastatic
renal
cell
carcinoma
and
thyroid
cancer.
Nonetheless,
poor
pharmacokinetic
properties
including
water
solubility
rapid
metabolic,
complex
tumor
microenvironment,
drug
resistance
have
impeded
its
satisfactory
therapeutic
efficacy.
This
article
comprehensively
reviews
the
uses
of
nanotechnology
in
LVN
to
improve
antitumor
effects.
With
characteristic
high
modifiability
loading
capacity
nano-drug
delivery
system,
an
active
targeting
approach,
controllable
release,
biomimetic
strategies
been
devised
deliver
target
tumors
sequence,
compensating
lack
passive
targeting.
The
existing
applications
advances
improving
efficacy
include
longer-term
efficiency,
achieving
higher
combination
therapy,
tracking
diagnosing
application
reducing
toxicity.
Therefore,
using
multiple
combined
with
photothermal,
photodynamic,
immunoregulatory
therapies
overcomes
multi-drug
resistance,
regulates
unfavorable
yields
synergistic
In
brief,
nano-LVN
system
has
brought
light
war
against
cancer
while
at
same
time
effect.
More
intelligent
multifunctional
nanoparticles
should
be
investigated
further
converted
into
clinical
future.
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Feb. 7, 2025
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
common
malignant
tumors
with
high
morbidity
and
mortality
worldwide.
Angiogenesis
essential
for
HCC
progression
metastasis.
Some
angiogenesis-related
genes
promote
this
process,
whereas
other
antiangiogenic
inhibit
growth
Therefore,
finding
new
potential
biomarkers
prognosis
prediction
treatment
essential.
Public
RNAseq
clinical
data
from
TCGA
GEO
database,
download
GeneCards,
MSigDB
through
single
factor
analysis
Cox,
LASSO
build
risk
score-Cox
regression
model
external
validation
verified
GEO.
Cox
analysis,
Kaplan
Meier
(KM)
curve,
ROC
decision-curve
will
be
used
to
evaluate
examine
score
effect
model.
GSVA
was
assess
variation
gene
sets
between
groups,
ClBERSOFT,
ESTIMATE,
TIMER
databases
were
analyze
immune
infiltration
in
single-cell
level
expression
differences
cells.
Finally,
three
pairs
tissues
tissue
adjacent
by
real-time
fluorescent
quantitative
PCR
(qRT_PCR)
western
blotting
(WB)
(ATP2A3
AEBP1
PNMA1,
PLAT)
HCC,
knocked
out
HCCLM3
cells,
which
study
biological
function
HCC.
We
established
a
prognostic
assessment
based
on
13
significant
associated
LASSO-Cox
analysis.
The
median
divide
these
patients
into
high-risk
low-risk
group
worse
than
that
group.
Through
multivariate
it
found
an
independent
predictor
overall
survival
(OS).
suggested
predicted
population
showed
higher
activity
purine,
pyrimidine,
riboflavin
metabolic
pathways.
Compared
group,
tumor
microenvironment
reduction
number
cells
promoting
anti-tumor
immunity
increase
inhibiting
immunity,
as
well
matrix
components.
On
level,
confirmed
key
(AEBP1,
ATP2A3,
PLAT,
PNMA1)
expressed
differently
liver
cancer
cell
groups.
qRT_PCR
WB
results
AEBP1,
PLAT
highly
compared
tissue,
proliferation,
migration,
invasion
inhibited
after
knocking
AEBP1.
constructed
novel
models
has
guide
development
more
personalized
strategies
patients.
In
addition,
therapeutic
target
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Oct. 10, 2023
This
study
aimed
to
examine
glycolysis/gluconeogenesis-related
genes
in
hepatocellular
carcinoma
(HCC)
and
evaluate
their
potential
roles
HCC
progression
immunotherapy
response.Data
analyzed
this
were
collected
from
GSE14520,
GSE76427,
GSE174570,
The
Cancer
Genome
Atlas
(TCGA),
PXD006512,
GSE149614
datasets,
metabolic
pathways
MSigDB
database.
Differentially
expressed
(DEGs)
identified
between
controls.
(candidate
genes)
obtained
consensus
clustering
was
performed
based
on
the
expression
of
candidate
genes.
Bioinformatics
analysis
used
screen
prognostic
Finally,
key
results
tested
patients.Thirteen
differentially
validated
additional
datasets.
Consensus
two
distinct
patient
clusters
(C1
C2)
with
different
prognoses
immune
microenvironments.
Immune
score
tumor
purity
significantly
higher
C1
than
C2,
CD4+
memory
activated
T
cell,
Tfh,
Tregs,
macrophage
M0
infiltrated
group.
also
five
intersecting
DEGs
TCGA,
GSE141198
as
genes,
which
had
a
protective
role
prognosis.
Compared
control
group,
all
showed
decreased
patients
RT-qPCR
Western
blot
analyses.
Flow
cytometry
verified
abnormal
infiltration
level
cells
patients.Results
that
associated
prognosis,
microenvironment,
response
HCC.
It
suggests
model
may
valuable
for
predicting
prognosis
patients.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(4), P. e0301663 - e0301663
Published: April 11, 2024
The
multikinase
inhibitor
sorafenib
is
the
standard
first-line
treatment
for
advanced
hepatocellular
carcinoma
(HCC),
but
many
patients
become
sorafenib-resistant
(SR).
This
study
investigated
efficacy
of
another
kinase
inhibitor,
regorafenib
(Rego),
as
a
second-line
treatment.
We
produced
SR
HCC
cells,
wherein
PI3K-Akt,
TNF,
cAMP,
and
TGF-beta
signaling
pathways
were
affected.
Acute
Rego
these
cells
reversed
expression
genes
involved
in
further
increased
PI3K-Akt
signaling.
Additionally,
nucleosome
assembly
epigenetic
gene
expression.
Weighted
co-expression
network
analysis
(WGCNA)
revealed
four
differentially
expressed
long
non-coding
RNA
(DElncRNA)
modules
that
associated
with
effectiveness
on
cells.
Eleven
putative
DElncRNAs
distinct
patterns
identified.
each
module
DEmRNAs
same
pattern,
thus
obtaining
DElncRNA/DEmRNA
modules.
discuss
potential
significance
module.
These
findings
provide
insights
resources
investigation
into
mechanisms
underlying
response
to
Rego.
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
167, P. 115561 - 115561
Published: Sept. 25, 2023
Hepatocellular
carcinoma
(HCC),
the
sixth
most
common
cancer
worldwide,
is
associated
with
a
high
degree
of
malignancy
and
poor
prognosis.
Patients
early
HCC
may
benefit
from
surgical
resection
to
remove
tumor
tissue
margin
healthy
surrounding
it.
Unfortunately,
patients
are
diagnosed
at
an
advanced
or
distant
stage,
which
point
not
feasible.
Systemic
therapy
now
routinely
prescribed
HCC;
however,
drug
resistance
has
become
major
obstacle
treatment
exploring
purported
mechanisms
promoting
remains
challenge.
Here,
we
focus
on
determinants
perspective
non-coding
RNAs
(ncRNAs),
liver
stem
cells
(LCSCs),
autophagy,
epithelial-mesenchymal
transition
(EMT),
exosomes,
ferroptosis,
microenvironment
(TME),
aim
provide
new
insights
into
treatment.
World Journal of Hepatology,
Journal Year:
2024,
Volume and Issue:
16(5), P. 716 - 730
Published: May 22, 2024
Liver
cancer,
primarily
hepatocellular
carcinoma,
remains
a
global
health
challenge
with
rising
incidence
and
limited
therapeutic
options.
Genetic
factors
play
pivotal
role
in
the
development
progression
of
liver
cancer.
This
state-of-the-art
paper
provides
comprehensive
review
current
landscape
genetic
screening
strategies
for
We
discuss
underpinnings
emphasizing
critical
risk-associated
variants,
somatic
mutations,
epigenetic
alterations.
also
explore
intricate
interplay
between
environmental
genetics,
highlighting
how
can
aid
risk
stratification
early
detection
Heliyon,
Journal Year:
2024,
Volume and Issue:
10(13), P. e34012 - e34012
Published: July 1, 2024
BackgroundCurrently,
there
are
few
studies
on
immune-related
prognostic
analysis
of
hepatocellular
carcinoma
(HCC).
Our
aim
was
to
establish
an
immune-correlated
model
for
HCC.MethodsImmune-associated
cells
were
obtained
from
the
scRNA-seq
dataset
(GSE149614)
HCC.
Differentially
expressed
genes
between
normal
and
tumor
immune-associated
ImmPort
database
used
identify
differentially
(IRDEGs).
Subsequently,
risk
established
in
TCGA-LIHC
cohort
(n
=
438)
Cancer
Genome
Atlas
(TCGA)
by
using
Kaplan-Meier
(K-M)
survival
curve,
univariate/multivariate
Cox
regression
analysis.
we
further
analyzed
immune
microenvironment
characteristics,
somatic
mutation,
checkpoint
its
ligand
expression
levels
high-
low-risk
groups,
as
well
drug
sensitivity
prediction.
ICGC
set
validation
cohort.
three
independent
Gene
Expression
Omnibus
(GEO)
datasets
(GSE54236,
GSE14520,
GSE64041)
verify
IRDEGs
expression,
PCR
assays
clinical
samples.ResultsThe
composed
4
genes,
namely
B2M,
SPP1,
PPIA,
HRG.
The
438
HCC
patients
divided
into
group.
high-risk
group
associated
with
poor
prognosis,
including
higher
T
stage,
advanced
pathological
stages,
less
cell
infiltration,
TP53
mutation
rate,
high
CTLA4
HAVCR2.
Besides,
populations
benefit
most
chemotherapy
drugs.
Similarly,
performance
validated
ICGC.
All
four
(TCGA-LIHC
cohort,
GSE54236,
q-PCR
results
demonstrated
that,
compared
samples,
expressions
B2M
HRG
lower
SPP1
higher.ConclusionIn
summary,
signature
had
a
good
predictive
prognosis
immunotherapy
patients.
