Cancers,
Год журнала:
2024,
Номер
16(24), С. 4239 - 4239
Опубликована: Дек. 19, 2024
Among
solid
tumors,
cholangiocarcinoma
(CCA)
emerges
as
one
of
the
most
difficult
to
eradicate.
The
silent
and
asymptomatic
nature
this
tumor,
particularly
in
its
early
stages,
well
high
heterogeneity
at
genomic,
epigenetic,
molecular
levels
delay
diagnosis,
significantly
compromising
efficacy
current
therapeutic
options
thus
contributing
a
dismal
prognosis.
Extensive
research
has
been
conducted
on
pathobiology
CCA,
recent
advances
have
made
classification
characterization
new
targets.
Both
targeted
therapy
immunotherapy
emerged
effective
safe
strategies
for
various
types
cancers,
demonstrating
potential
benefits
advanced
CCA.
Furthermore,
deeper
comprehension
cellular
components
tumor
microenvironment
(TME)
opened
up
possibilities
innovative
treatment
methods.
This
review
discusses
evidence
biology
highlighting
novel
possible
druggable
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Ноя. 28, 2023
Natural
killer
(NK)
cells
integrate
heterogeneous
signals
for
activation
and
inhibition
using
germline-encoded
receptors.
These
receptors
are
stochastically
co-expressed,
their
concurrent
engagement
signaling
can
adjust
the
sensitivity
of
individual
to
putative
targets.
Against
cancers,
which
mutate
evolve
under
therapeutic
immunologic
pressure,
diversity
recognition
provided
by
NK
may
be
key
comprehensive
cancer
control.
already
being
trialled
as
adoptive
cell
therapy
targets
immunotherapeutic
agents.
However,
strategies
leverage
naturally
occurring
agility
have
not
yet
been
developed.
In
this
review,
we
discuss
pathways
through
or
generated
in
cells,
focusing
on
roles
potential
immunotherapies.
Finally,
consider
impacts
receptor
co-expression
engage
multiple
reactivity
maximize
scope
strength
antitumor
activities.
Cancer Management and Research,
Год журнала:
2024,
Номер
Volume 16, С. 941 - 963
Опубликована: Июль 1, 2024
Biliary
tract
cancer
(BTC)
represents
a
challenging
malignancy
characterized
by
aggressive
behavior,
high
relapse
rates,
and
poor
prognosis.
In
recent
years,
immunotherapy
has
revolutionized
the
treatment
landscape
for
various
cancers,
but
its
efficacy
in
BTC
remains
limited.
This
article
provides
comprehensive
overview
of
advances
preclinical
clinical
studies
BTC.
We
explore
potential
immune
checkpoint
inhibitors
reshaping
management
Despite
disappointing
results
thus
far,
ongoing
trials
are
investigating
combination
with
other
modalities.
Furthermore,
research
on
tumor
microenvironment
unveiled
novel
targets
immunotherapeutic
interventions.
By
understanding
current
state
highlighting
future
directions,
this
aims
to
fuel
further
exploration
ultimately
improve
patient
outcomes
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 12, 2023
Abstract
Lymphangioleiomyomatosis
(LAM)
is
a
progressive
lung
disease
with
limited
treatments,
largely
due
to
an
incomplete
understanding
of
its
pathogenesis.
Lymphatic
endothelial
cells
(LECs)
invade
LAM
cell
clusters,
which
include
HMB-45-positive
epithelioid
and
smooth
muscle
α-actin-expressing
LAM-associated
fibroblasts
(LAMFs).
Recent
evidence
shows
that
LAMFs
resemble
cancer-associated
fibroblasts,
LAMF-LEC
interactions
contributing
progression.
To
explore
these
mechanisms,
we
used
spatial
transcriptomics
on
tissues
identified
gene
cluster
enriched
in
kinase
signaling
pathways
linked
myofibroblasts
co-expressed
LEC
markers.
Kinase
arrays
revealed
elevated
PDGFR
FGFR
LAMFs.
Using
3D
co-culture
spheroid
model
primary
LECs,
observed
increased
invasion
spheroids
compared
non-LAM
fibroblasts.
Treatment
sorafenib,
multikinase
inhibitor,
significantly
reduced
invasion,
outperforming
Rapamycin.
We
also
confirmed
TSC2-null
AML
as
key
VEGF-A
secretors,
was
suppressed
by
sorafenib
both
These
findings
highlight
bFGF
potential
therapeutic
targets
suggest
inhibition
promising
strategy
for
LAM.
One
Sentence
Summary
transcriptomics,
LECs
contributors
LAM,
BMC Medical Genomics,
Год журнала:
2023,
Номер
16(1)
Опубликована: Окт. 11, 2023
Abstract
Background
Gallbladder
carcinoma
(GBC)
is
a
highly
malignant
tumor
with
poor
overall
prognosis.
This
study
aimed
to
identify
the
characteristic
microRNAs
(miRNAs)
of
GBC
and
competing
endogenous
RNA
(ceRNA)
regulatory
mechanisms.
Methods
The
microarray
data
tissue
samples
normal
gallbladder
(NGB)
from
Gene
Expression
Omnibus
(GEO)
database
was
downloaded.
GBC-related
differentially
expressed
miRNAs
(DE-miRNAs)
were
identified
by
inter-group
differential
expression
analysis
weighted
gene
co-expression
network
(WGCNA).
Machine
learning
algorithms
used
screen
miRNA
based
on
intersect
between
least
absolute
shrinkage
selection
operator
(LASSO)
Support
vector
machine-recursive
feature
elimination
(SVM-RFE).
Based
GEO
database,
ceRNA
predicted
constructed.
biological
functions
revealed
carrying
out
enrichment
implemented.
We
further
screened
key
genes
constructed
protein-protein
interaction
(PPI)
network,
generated
transcription
factors
(TFs)
signature
miRNAs.
in
clinical
verified
quantitative
real-time
polymerase
chain
reaction
(qRT-PCR).
Results
A
total
131
DE-miRNAs
obtained.
hsa-miR-4770
defined
as
for
GBC.
containing
211
mRNAs,
one
miRNA,
two
lncRNAs,
48
circRNAs
created.
suggested
that
downstream
mainly
involved
actin
filament
organization,
cell-substrate
adhesion,
cell-matrix
reactive
oxygen
species
metabolic
process,
glutamine
process
extracellular
matrix
(ECM)-receptor
pathway.
10
found
be
most
correlated
disease,
cell
cycle-related
processes,
p53,
extrinsic
apoptotic
signaling
pathways.
qRT-PCR
result
demonstrated
down-regulated
GBC,
trend
consistent
public
database.
Conclusions
may
play
roles
provided
some
basis
potential
pathogenesis
JHEP Reports,
Год журнала:
2024,
Номер
7(3), С. 101275 - 101275
Опубликована: Ноя. 15, 2024
Lymph
node
metastasis
(LNM)
is
a
major
determinant
of
recurrence
and
prognosis
in
intrahepatic
cholangiocarcinoma
(iCCA).
LNM
disrupts
T
cell-mediated
cytotoxicity,
promotes
tumor-specific
immune
tolerance,
facilitates
distant
metastasis.
Despite
its
importance,
extensive
research
on
LMN
iCCA
lacking.
This
study
aimed
to
systematically
explore
the
heterogeneity
LNM-associated
microenvironment
by
integrating
single-cell
multi-omics
analyses,
identifying
metastasis-associated
cell
subgroups,
validating
these
findings
through
multiple
cohorts.
We
analyzed
transcriptomics
data
from
primary
tumors,
cancer-adjacent
liver
tissues,
tumor-draining
lymph
nodes
four
patients
with
who
underwent
radical
surgery.
Additionally,
we
collected
81
tumor
matched
tissue
sections
iCCA.
performed
RNA
sequencing
multiplex
immunohistochemistry,
followed
differential
gene
expression
analysis,
functional
enrichment
copy
number
variation
assessment,
pseudotime
analysis.
Our
analysis
revealed
complex
microenvironment.
found
significant
increase
stromal
mature
cells
metastatic
nodes.
constitute
predominant
component,
diverse
subtypes.
identified
CD36+
macrophages
SAA1+
as
key
players
process.
The
SAA1-CD36
receptor‒ligand
pair
may
be
crucial
forming
several
subgroups.
These
provide
new
insights
into
mechanisms
underlying
lay
groundwork
for
development
novel
therapeutic
strategies.
highlights
importance
technologies
understanding
complexity
offers
valuable
resources
future
research.
lack
transcriptome
(iCCA)
metastases
has
prevented
us
disease
progression.
To
fill
this
knowledge
gap,
elucidated
unique
ecosystem
metastases,
which
an
important
advance
clarifying
impact
environment
disease.
results
LNM-related
targets,
will
not
only
helpful
basic
researchers,
but
also
potential
diagnostic
treatment
ideas
physicians,
thereby
helping
their
caregivers
develop
more
personalized
plans.
finding
highly
improving
advanced
future.
Cancers,
Год журнала:
2024,
Номер
16(24), С. 4239 - 4239
Опубликована: Дек. 19, 2024
Among
solid
tumors,
cholangiocarcinoma
(CCA)
emerges
as
one
of
the
most
difficult
to
eradicate.
The
silent
and
asymptomatic
nature
this
tumor,
particularly
in
its
early
stages,
well
high
heterogeneity
at
genomic,
epigenetic,
molecular
levels
delay
diagnosis,
significantly
compromising
efficacy
current
therapeutic
options
thus
contributing
a
dismal
prognosis.
Extensive
research
has
been
conducted
on
pathobiology
CCA,
recent
advances
have
made
classification
characterization
new
targets.
Both
targeted
therapy
immunotherapy
emerged
effective
safe
strategies
for
various
types
cancers,
demonstrating
potential
benefits
advanced
CCA.
Furthermore,
deeper
comprehension
cellular
components
tumor
microenvironment
(TME)
opened
up
possibilities
innovative
treatment
methods.
This
review
discusses
evidence
biology
highlighting
novel
possible
druggable
