bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
Solid
tumors
often
have
an
abundance
of
collagen-I
that
stiffens
the
tissue,
and
they
are
invariably
driven
by
mutations
include
chromosome
losses
gains.
These
observations
linked
here
showing
3D
matrix
stiffness
induces
heritable
changes
to
a
cell
’
s
DNA.
We
use
live-cell
reporters
(ChReporters)
hydrogels
tunable
show
mitotic
compression,
micronuclei
counts,
ChReporter
heterogeneity
all
increase
as
functions
stiffness.
Increased
mistakes
occur
despite
suppressed
division
in
stiff
minimal
size
variation
between
spheroids.
Colonies
ChReporter-negative
cells
within
cancer
spheroids
align
with
Luria-Delbruck
seminal
theory
for
mutations,
which
predicts
inter-spheroid
variances
exceed
Poisson
statistics.
Suppression
contractility
motor
Myosin-II
also
increases
loss
but
not
2D
does
affect
spheroid
growth
–
thus
clarifying
putative
role
tumor
suppressor.
Consistent
experiments,
pan-cancer
analyses
clinical
data
associates
gains
levels
genetic
variation.
Stiff
extracellular
drives
mechano-evolution
solid
Darwin-Lamarck
process
complicates
therapy.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 6, 2024
Abstract
The
paradigm
for
macrophage
characterization
has
evolved
from
the
simple
M1/M2
dichotomy
to
a
more
complex
model
that
encompasses
broad
spectrum
of
phenotypic
diversity,
due
differences
in
ontogeny
and/or
local
stimuli.
We
currently
lack
an
in-depth
pan-cancer
single
cell
RNA-seq
(scRNAseq)
atlas
tumour-associated
macrophages
(TAMs)
fully
captures
this
complexity.
In
addition,
increased
understanding
diversity
could
help
explain
variable
responses
cancer
patients
immunotherapy.
Our
includes
well
established
subsets
as
number
additional
ones.
associate
composition
with
tumour
phenotype
and
show
can
vary
between
primary
metastatic
tumours
growing
sites
like
liver.
also
examine
macrophage-T
functional
cross
talk
identify
two
TAMs
associated
T
activation.
Analysis
TAM
signatures
large
cohort
immune
checkpoint
inhibitor-treated
(CPI1000
+
)
multiple
response,
including
presence
subset
upregulate
collagen-related
genes.
Finally,
we
demonstrate
utility
our
data
resource
reference
mapping
novel
datasets
using
projection.
Overall,
these
advances
represent
important
step
both
classification
overcoming
resistance
immunotherapies
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Фев. 18, 2025
Abstract
Breast
cancer,
characterized
by
unique
epidemiological
patterns
and
significant
heterogeneity,
remains
one
of
the
leading
causes
malignancy-related
deaths
in
women.
The
increasingly
nuanced
molecular
subtypes
breast
cancer
have
enhanced
comprehension
precision
treatment
this
disease.
mechanisms
tumorigenesis
progression
been
central
to
scientific
research,
with
investigations
spanning
various
perspectives
such
as
tumor
stemness,
intra-tumoral
microbiota,
circadian
rhythms.
Technological
advancements,
particularly
those
integrated
artificial
intelligence,
significantly
improved
accuracy
detection
diagnosis.
emergence
novel
therapeutic
concepts
drugs
represents
a
paradigm
shift
towards
personalized
medicine.
Evidence
suggests
that
optimal
diagnosis
models
tailored
individual
patient
risk
expected
are
crucial,
supporting
era
oncology
for
cancer.
Despite
rapid
advancements
increasing
emphasis
on
clinical
comprehensive
update
summary
panoramic
knowledge
related
disease
needed.
In
review,
we
provide
thorough
overview
global
status
including
its
epidemiology,
factors,
pathophysiology,
subtyping.
Additionally,
elaborate
latest
research
into
contributing
progression,
emerging
strategies,
long-term
management.
This
review
offers
valuable
insights
Cancer
Research,
thereby
facilitating
future
progress
both
basic
application.
Experimental Hematology and Oncology,
Год журнала:
2025,
Номер
14(1)
Опубликована: Янв. 11, 2025
Abstract
Immune
checkpoint
therapies
have
spearheaded
drug
innovation
over
the
last
decade,
propelling
cancer
treatments
toward
a
new
era
of
precision
therapies.
Nonetheless,
challenges
low
response
rates
and
prevalent
resistance
underscore
imperative
for
deeper
understanding
tumor
microenvironment
(TME)
pursuit
novel
targets.
Recent
findings
revealed
profound
impacts
biomechanical
forces
within
on
immune
surveillance
progression
in
both
murine
models
clinical
settings.
Furthermore,
pharmacological
or
genetic
manipulation
mechanical
checkpoints,
such
as
PIEZO1,
DDR1,
YAP/TAZ,
TRPV4,
has
shown
remarkable
potential
activation
eradication
tumors.
In
this
review,
we
delved
into
underlying
mechanisms
resulting
intricate
biological
meaning
TME,
focusing
mainly
extracellular
matrix,
stiffness
cells,
synapses.
We
also
summarized
methodologies
employed
research
translation
derived
from
current
evidence.
This
comprehensive
review
biomechanics
will
enhance
functional
role
provide
basic
knowledge
discovery
therapeutic
The EMBO Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 7, 2025
Abstract
L-arginine
is
the
most
nitrogen-rich
amino
acid,
acting
as
a
key
precursor
for
synthesis
of
nitrogen-containing
metabolites
and
an
essential
intermediate
in
clearance
excess
nitrogen.
Arginine’s
side
chain
possesses
guanidino
group
which
has
unique
biochemical
properties,
plays
primary
role
nitrogen
excretion
(urea),
cellular
signaling
(nitric
oxide)
energy
buffering
(phosphocreatine).
The
post-translational
modification
protein-incorporated
arginine
by
guanidino-group
methylation
also
contributes
to
epigenetic
gene
control.
Most
human
cells
do
not
synthesize
sufficient
meet
demand
are
dependent
on
exogenous
arginine.
Thus,
dietary
important
maintaining
health,
particularly
upon
physiologic
stress.
How
adapt
changes
extracellular
availability
unclear,
mostly
because
nearly
all
tissue
culture
media
supplemented
with
supraphysiologic
levels
Evidence
emerging
that
arginine-deficiency
can
influence
disease
progression.
Here,
we
review
new
insights
into
importance
metabolite,
emphasizing
central
mitochondria
synthesis/catabolism
recent
discovery
act
molecule
regulating
expression
organelle
dynamics.
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Фев. 17, 2025
Cancer
continues
to
be
a
major
global
health
burden,
with
high
morbidity
and
mortality.
Building
on
the
success
of
immune
checkpoint
inhibitors
adoptive
cellular
therapy,
cancer
vaccines
have
garnered
significant
interest,
but
their
clinical
remains
modest.
Benefiting
from
advancements
in
technology,
many
meticulously
designed
shown
promise,
warranting
further
investigations
reach
full
potential.
hold
unique
benefits,
particularly
for
patients
resistant
other
therapies,
they
offer
ability
initiate
broad
durable
T
cell
responses.
In
this
review,
we
highlight
antigen
selection
vaccines,
introduce
responses
induced
by
propose
strategies
enhance
vaccine
immunogenicity.
Furthermore,
summarize
key
features
notable
advances
various
platforms.
Lastly,
delve
into
mechanisms
tumor
resistance
explore
potential
benefits
combining
standard
treatments
immunomodulatory
approaches
improve
efficacy.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 7, 2025
Abstract
Macrophages
are
immune
cells
belonging
to
the
mononuclear
phagocyte
system.
They
play
crucial
roles
in
defense,
surveillance,
and
homeostasis.
This
review
systematically
discusses
types
of
hematopoietic
progenitors
that
give
rise
macrophages,
including
primitive
progenitors,
erythro-myeloid
stem
cells.
These
have
distinct
genetic
backgrounds
developmental
processes.
Accordingly,
macrophages
exhibit
complex
diverse
functions
body,
phagocytosis
clearance
cellular
debris,
antigen
presentation,
response,
regulation
inflammation
cytokine
production,
tissue
remodeling
repair,
multi-level
regulatory
signaling
pathways/crosstalk
involved
homeostasis
physiology.
Besides,
tumor-associated
a
key
component
TME,
exhibiting
both
anti-tumor
pro-tumor
properties.
Furthermore,
functional
status
is
closely
linked
development
various
diseases,
cancer,
autoimmune
disorders,
cardiovascular
disease,
neurodegenerative
metabolic
conditions,
trauma.
Targeting
has
emerged
as
promising
therapeutic
strategy
these
contexts.
Clinical
trials
macrophage-based
targeted
drugs,
immunotherapies,
nanoparticle-based
therapy
were
comprehensively
summarized.
Potential
challenges
future
directions
targeting
also
been
discussed.
Overall,
our
highlights
significance
this
versatile
cell
human
health
which
expected
inform
research
clinical
practice.
