Frontiers in Molecular Biosciences,
Год журнала:
2025,
Номер
11
Опубликована: Янв. 3, 2025
Long
non-coding
RNAs
(lncRNAs)
are
crucial
regulatory
molecules
that
participate
in
numerous
cellular
development
processes,
and
they
have
gathered
much
interest
recently.
HOXA10
antisense
RNA
(HOXA10-AS,
also
known
as
HOXA-AS4)
is
a
novel
lncRNA
was
identified
to
be
dysregulated
some
prevalent
malignancies.
In
this
review,
the
clinical
significance
of
HOXA10-AS
for
prognosis
various
cancers
analyzed.
addition,
major
advances
our
understanding
biological
functions
mechanisms
different
human
summarized.
These
include
esophageal
carcinoma
(ESCA),
gastric
cancer
(GC),
glioma,
laryngeal
squamous
cell
(LSCC),
acute
myeloid
leukemia
(AML),
lung
adenocarcinoma
(LUAD),
nasopharyngeal
(NPC),
oral
(OSCC),
pancreatic
cancer.
We
note
aberrant
expression
promotes
malignant
progression
through
underlying
mechanisms.
conclusion,
expected
serve
an
ideal
biomarker
effective
therapy
target.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Сен. 3, 2024
Abstract
Claudin18.2
(CLDN18.2)
is
overexpressed
in
cancers
of
the
digestive
system,
rendering
it
an
ideal
drug
target
for
antibody-drug
conjugates
(ADCs).
Despite
many
CLDN18.2-directed
ADCs
undergoing
clinical
trials,
inconclusive
underlying
mechanisms
pose
a
hurdle
to
extending
utility
these
agents.
In
our
study,
αCLDN18.2-MMAE,
ADC
composed
anti-CLDN18.2
monoclonal
antibody
and
tubulin
inhibitor
MMAE,
induced
dose-dependent
apoptosis
via
cleavage
caspase-9/PARP
proteins
CLDN18.2-positive
gastric
cancer
cells.
It
was
worth
noting
that
autophagy
remarkably
activated
during
αCLDN18.2-MMAE
treatment,
which
characterized
by
accumulation
autophagosomes,
conversion
marker
LC3
from
its
form
I
II,
complete
autophagic
flux.
Inhibiting
LY294002
enhanced
αCLDN18.2-MMAE-induced
cytotoxicity
caspase-mediated
apoptosis,
indicating
cytoprotective
role
ADC-treated
Combination
with
significantly
potentiated
vivo
antitumoral
efficacy
αCLDN18.2-MMAE.
Besides,
Akt/mTOR
pathway
inactivation
demonstrated
be
implicated
initiation
αCLDN18.2-MMAE-treated
conclusion,
study
highlighted
groundbreaking
investigation
into
mechanism
ADC,
focusing
on
crucial
autophagy,
providing
novel
insight
treat
combination
inhibitor.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 18, 2025
Gastric
cancer
is
a
highly
aggressive
malignancy
characterized
by
complex
tumor
microenvironment
(TME).
Cancer-associated
fibroblasts
(CAFs),
which
are
key
component
of
the
TME,
exhibit
significant
heterogeneity
and
play
crucial
roles
in
progression.
Therefore,
comprehensive
understanding
CAFs
essential
for
developing
novel
therapeutic
strategies
gastric
cancer.
This
study
investigates
characteristics
functional
information
CAF
subtypes
explores
intercellular
communication
between
malignant
epithelial
cells
(ECs)
analyzing
single-cell
sequencing
data
from
24
samples.
CellChat
was
employed
to
map
communication,
Seurat
used
integrate
with
spatial
transcriptome
reconstruct
map.
The
relationship
apCAFs
analyzed
using
multicolor
immunohistochemistry.
Cells
were
categorized
into
nine
distinct
categories,
revealing
positive
correlation
proportions
fibroblasts.
Furthermore,
six
fibroblast
subpopulations
identified:
inflammatory
(iCAFs),
pericytes,
matrix
(mCAFs),
antigen-presenting
(apCAFs),
smooth
muscle
(SMCs),
proliferative
(pCAFs).
Each
these
linked
various
biological
processes
immune
responses.
Malignant
ECs
exhibited
heightened
particularly
subpopulations,
through
specific
ligand-receptor
interactions.
High-density
regions
displayed
exclusivity,
pericytes
serving
as
source
iCAFs,
mCAFs,
apCAFs.
Notably,
showed
increased
interactions,
certain
pairs
potentially
impacting
prognosis
Multiplex
immunohistochemistry
(mIHC)
confirmed
close
proximity
Our
provided
characterization
revealed
intricate
networks
within
TME.
identified
their
interactions
could
serve
potential
targets.
Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 7, 2025
Abstract
Gastric
cancer
(GC)
remains
a
leading
cause
of
cancer-related
mortality
worldwide,
with
limited
treatment
options
in
advanced
stages.
Immunotherapy,
particularly
immune
checkpoint
inhibitors
(ICIs)
targeting
PD1/PD-L1,
has
emerged
as
promising
therapeutic
approach.
However,
significant
proportion
patients
exhibit
primary
or
acquired
resistance,
limiting
the
overall
efficacy
immunotherapy.
This
review
provides
comprehensive
analysis
mechanisms
underlying
immunotherapy
resistance
GC,
including
role
tumor
microenvironment,
dynamic
PD-L1
expression,
compensatory
activation
other
checkpoints,
and
genomic
instability.
Furthermore,
explores
GC-specific
factors
such
molecular
subtypes,
unique
evasion
mechanisms,
impact
Helicobacter
pylori
infection.
We
also
discuss
emerging
strategies
to
overcome
combination
therapies,
novel
immunotherapeutic
approaches,
personalized
based
on
genomics
microenvironment.
By
highlighting
these
key
areas,
this
aims
inform
future
research
directions
clinical
practice,
ultimately
improving
outcomes
for
GC
undergoing
World Journal of Gastrointestinal Surgery,
Год журнала:
2024,
Номер
16(3), С. 700 - 709
Опубликована: Март 21, 2024
Gastric
cancer
(GC)
is
the
fifth
most
common
type
of
and
has
fourth
highest
death
rate
among
all
cancers.
There
a
lack
studies
examining
impact
liver
metastases
on
effectiveness
immunotherapy
in
individuals
diagnosed
with
GC.
Current
in
vitro
models
for
gastric
cancer
research,
such
as
2D
cell
cultures
and
organoid
systems,
often
fail
to
replicate
the
complex
extracellular
matrix
(ECM)
found
vivo.
For
first
time,
this
study
utilizes
a
gelatin
methacryloyl
(GelMA)
hydrogel,
biomimetic
ECM-like
material,
3D
bioprinting
construct
physiologically
relevant
model.
GelMA's
tunable
mechanical
properties
allow
precise
manipulation
of
cellular
behavior
within
physiological
ranges.
Genetic
phenotypic
analyses
indicate
that
bioprinted
GelMA
(3Db)
model
accurately
mimics
clinical
tumor
characteristics
reproduces
key
hallmarks,
proliferation,
invasion,
migration,
angiogenesis,
Warburg
effect.
Comparisons
gene
expression
drug
responses
between
3Db
patient-derived
xenograft
models,
both
constructed
from
primary
cells,
validate
model's
relevance.
The
ability
closely
simulate
vivo
conditions
highlights
its
crucial
role
identifying
treatment
targets
predicting
patient-specific
responses,
showcasing
potential
high-throughput
screening
applications.
This
is
report
pivotal
GelMA-based
advancing
research
regenerative
medicine.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 5, 2025
Stomach
adenocarcinoma
(STAD)
is
the
most
prevalent
gastrointestinal
malignancy
and
seriously
threatens
life
of
global
population.
Anoikis,
a
process
programmed
cell
death
that
occurs
when
cells
detach
from
extracellular
matrix,
closely
associated
with
tumor
invasion
metastasis.
In
this
study,
we
used
TCGA-STAD
database
to
identify
expression
patterns
prognostic
relevance
anoikis-related
genes
(ARGs)
in
STAD.
Functional
enrichment
analysis
was
explore
potential
pathway.
LASSO
Cox
regression
were
construct
signature.
The
anoikis
risk
score
(ARS)
incorporated
7
stratified
patients
into
highand
low-risk
subgroups
by
median
value
splitting.
addition,
external
validation
performed
based
on
GSE66229,
GSE15459,
GSE84437
cohorts.
Nomograms
created
characteristics
combination
clinical
variants
performance
model
validated
time-dependent
AUC,
calibration
curves,
decision
curve
(DCA).
signature
indicated
subgroup
had
better
outcomes
significant
correlations
microenvironment,
immune
landscape,
immunotherapy
response,
drug
sensitivity.
single-cell
displayed
types,
subcellular
localization
genes,
cellular
interaction
reveal
molecular
communication
mechanism
resistance.
Finally,
vitro
experiments
confirmed
critical
role
CRABP2
results
knockdown
inhibited
gastric
cancer
proliferation,
migration
invasion,
promoted
apoptosis.
summary,
ARS
can
serve
as
biomarker
for
predicting
survival
STAD
patients,
providing
new
tools
personalized
treatment
decisions
patients.