Abstract
Background
The
incidence
of
alcohol‐associated
cancers
is
higher
within
Asian
populations
having
an
increased
prevalence
inactivating
mutation
in
aldehyde
dehydrogenase
2
(
ALDH2
),
a
mitochondrial
enzyme
required
for
the
clearance
acetaldehyde,
cytotoxic
metabolite
ethanol.
role
alcohol
consumption
promoting
lung
cancer
controversial,
and
little
attention
has
been
paid
to
association
between
drinking
pulmonary
expression.
Methods
We
performed
comprehensive
bioinformatic
analysis
multi‐omics
data
available
public
databases
elucidate
adenocarcinoma
(LUAD).
Results
Transcriptional
proteomic
indicate
substantial
expression
ALDH2,
which
functional
metabolism
diffused
from
bronchial
circulation.
healthy
tissue
than
LUAD
inhibits
cell
cycle,
apoptosis,
epithelial–mesenchymal
transition
pathways.
Moreover,
low
mRNA
levels
predict
poor
prognosis
overall
survival
patients.
Interestingly,
correlates
with
immune
infiltration
LUAD.
Conclusions
A
better
understanding
tumor
progression
might
support
its
potential
use
as
prognostic
marker
therapeutic
target
improving
immunotherapeutic
response.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 18, 2024
Immunotherapy
has
made
significant
strides
in
cancer
treatment
with
strategies
like
checkpoint
blockade
antibodies
and
adoptive
T
cell
transfer.
Chimeric
antigen
receptor
cells
(CAR-T)
have
emerged
as
a
promising
approach
to
combine
these
overcome
their
limitations.
This
review
explores
CAR-T
living
drug
for
treatment.
are
genetically
engineered
immune
designed
target
eliminate
tumor
by
recognizing
specific
antigens.
The
study
involves
comprehensive
literature
on
technology,
covering
structure
optimization,
generations,
manufacturing
processes,
gene
therapy
strategies.
It
examines
haematologic
cancers
solid
tumors,
highlighting
challenges
proposing
suicide
gene-based
mechanism
enhance
safety.
results
show
advancements
particularly
optimization
generation.
process
improved
broader
clinical
application.
However,
series
of
inherent
side
effects
still
need
be
addressed.
In
conclusion,
hold
great
promise
treatment,
but
ongoing
research
is
crucial
improve
efficacy
safety
oncology
patients.
proposed
offers
potential
solution
mitigate
including
cytokine
release
syndrome
(the
most
common
toxic
effect
therapy)
the
associated
neurotoxicity.
Journal of Clinical and Translational Hepatology,
Год журнала:
2024,
Номер
000(000), С. 000 - 000
Опубликована: Июнь 11, 2024
Tissue
inhibitor
of
metalloproteinase-1
(TIMP-1)
plays
a
role
in
the
excessive
generation
extracellular
matrix
liver
fibrosis.
This
study
aimed
to
explore
pathways
through
which
TIMP-1
controls
monocyte
chemoattractant
protein-1
(MCP-1)
expression
and
promotes
hepatic
macrophage
recruitment.
BackgroundLocally
advanced
rectal
cancer
(LARC)
is
treated
with
neoadjuvant
chemoradiotherapy
(nCRT)
followed
by
surgery,
achieving
pathological
complete
response
(pCR)
in
~15%
of
cases.
Enhancing
pCR
through
combined
nCRT
and
chemotherapy
increases
toxicity,
while
many
patients
fail
to
benefit
from
nCRT,
experiencing
significant
side
effects.
Predicting
could
enable
non-surgical
management
via
a
watch-and-wait
strategy
spare
non-responders
unnecessary
toxicity.
However,
no
gene
expression
signatures
predicting
have
yet
been
clinically
implemented.MethodsWe
conducted
differential
analysis
across
six
GEO
datasets
integrated
four
microarray
refine
findings.
Using
machine
learning,
we
developed
signature
predictive
validated
it
cross-validation.
Gene
set
enrichment
(GSEA)
identified
biological
pathways
linked
response.
Spatial
transcriptomic
profiling
using
GeoMx
Digital
Profiling
(DSP)
technology
was
performed
on
pre-treatment
biopsies
uncover
compartment-specific
markers
within
tumor
stroma.ResultsThe
achieved
strong
performance
(AUC
=
0.80)
GLMnet
Random
Forest
models
significantly
associated
consensus
molecular
subtypes
(CMS4)
immune
(iCMS3).
GSEA
revealed
related
VEGFR,
EGFR,
Toll-like
receptor
signaling.
transcriptomics
eight
genes,
tumor-associated
genes
showing
higher
value
than
stroma-associated
markers.ConclusionWe
present
novel
LARC
potential
guide
personalized
treatment.
highlights
the
microenvironment's
contribution
therapy
outcomes,
warranting
further
validation
larger
cohorts.
Pharmaceutics,
Год журнала:
2025,
Номер
17(6), С. 713 - 713
Опубликована: Май 28, 2025
Checkpoint
inhibitors
are
a
modern
therapeutic
approach
for
treating
various
types
of
cancer,
metabolic
diseases,
and
chronic
infections.
The
main
goal
this
therapy
is
to
specifically
unlock
the
immune
system,
allowing
it
recognize
eliminate
cancer
cells
or
pathogens,
primarily
through
activation
T
lymphocytes.
Monoclonal
antibodies
used
in
treatment
cancers,
such
as
pembrolizumab
(Keytruda),
nivolumab
(Opdivo),
ipilimumab
(Yervoy),
carry
several
limitations,
due
their
large
molecular
size.
challenges
include
limited
tissue
penetration,
long
half-life
body,
risk
autoimmune
responses.
Compared
antibodies,
small-molecule
peptide
offer
significant
advantages
related
structure.
These
drugs
demonstrate
better
ability
penetrate
hard-to-reach
areas,
tumor
microenvironments,
can
be
administered
orally,
often
show
lower
immunogenicity.
A
new
generation
PROTACs,
which
combine
direct
proteins
degradation
with
action
checkpoint
inhibitors,
contributing
elimination
responsible
suppressing
response.
This
publication
describes
PROTAC
molecules
targeting
negative
checkpoints—CTLA-4,
PD-1,
VISTA,
TIM-3,
BTLA-4,
LAG-3,
TIGIT.
