Deciphering the role of liquid-liquid phase separation in sarcoma: Implications for pathogenesis and treatment
Cancer Letters,
Год журнала:
2025,
Номер
616, С. 217585 - 217585
Опубликована: Фев. 23, 2025
Язык: Английский
RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
Abstract
Chemoresistance
represents
a
major
challenge
for
osteosarcoma
treatment.
Despite
the
improved
knowledge
of
cancer
biology,
core
determinants
cisplatin
(DDP)
resistance
in
remain
unclear
and
deserve
further
exploration.
Here,
RFWD3
is
identified
as
key
regulator
DDP
sensitivity
using
genome‐wide
CRISPR
screen.
It
demonstrated
that
overexpressed
post‐chemotherapy
tissues
compared
to
pre‐chemotherapy
tissues.
Knocking
out
increased
cells
Mechanistically,
bound
ubiquitinated
PHGDH
at
Lys137
residue,
promoting
its
degradation
conserving
cellular
oxidized
nicotinamide
adenine
dinucleotide
(NAD
+
).
The
resulting
surplus
NAD
enhanced
TCA
cycle,
leading
production
aspartic
acid
glutamic
de
novo
nucleotide
biosynthesis.
In
addition,
virtual
screening
techniques
are
employed
identify
Lomitapide
specific
inhibitor
RFWD3‐PHGDH
interaction,
capable
disrupting
binding
between
PHGDH.
found
exhibits
significant
synergistic
anti‐osteosarcoma
effect
when
combined
with
DDP.
conclusion,
role
regulating
metabolism
revealed
comprised
targetable
candidates
overcoming
chemoresistance
osteosarcoma.
Язык: Английский
Deep learning models in classifying primary bone tumors and bone infections based on radiographs
npj Precision Oncology,
Год журнала:
2025,
Номер
9(1)
Опубликована: Март 13, 2025
Primary
bone
tumors
(PBTs)
present
significant
diagnostic
challenges
due
to
their
heterogeneous
nature
and
similarities
with
infections.
This
study
aimed
develop
an
ensemble
deep
learning
framework
that
integrates
multicenter
radiographs
extensive
clinical
features
accurately
differentiate
between
PBTs
We
compared
the
performance
of
model
four
imaging
models
based
solely
on
utilizing
EfficientNet
B3,
B4,
Vision
Transformer,
Swin
Transformers.
The
patients
were
split
into
external
dataset
(N
=
423)
internal
[including
training
1044),
test
354),
validation
set
171)].
outperformed
models,
achieving
areas
under
curve
(AUCs)
0.948
0.963
sets,
respectively,
accuracies
0.881
0.895.
Its
surpassed
junior
mid-level
radiologists
was
comparable
senior
(accuracy:
83.6%).
These
findings
underscore
potential
in
enhancing
precision
for
infections
(Research
Registration
Unique
Identifying
Number
(UIN):
researchregistry10483
details
are
available
at
https://www.researchregistry.com/register-now#home/registrationdetails/6693845995ba110026aeb754/
).
Язык: Английский
LINC00942 Accelerates Esophageal Cancer Progression by Raising PRKDC Through Interaction With PTBP1
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2025,
Номер
39(3)
Опубликована: Март 1, 2025
ABSTRACT
Aberrantly
expressed
LINC00942
is
participated
in
the
progression
of
several
cancers.
However,
function
esophageal
cancer
(ESCA)
unclear.
The
objective
this
study
was
to
explore
effect
on
ESCA
and
its
possible
molecular
mechanisms.
First,
differentially
lncRNAs
were
analyzed
using
GSE192662
microarray.
catRAPID
omics
v2.1
applied
predict
proteins
that
might
interact
with
LINC00942.
SDS‐PAGE
silver
staining
assay,
RNA
pull
down,
RIP
assay
utilized
validate
interacting
Then,
seq
detect
downstream
targets
PTBP1,
KEGG
enrichment
analysis
used
analyze
genes
involved
proliferation
migration‐related
signaling
pathways.
In
addition,
CCK‐8,
EdU
transwell
impact
cell
function.
Bioinformatics
revealed
significantly
overexpressed
ESCA.
Patients
low‐expression
had
an
obviously
better
prognosis.
After
knockdown,
migration
TE‐1
OE19
dramatically
reduced.
Subsequently,
PTBP1
found
LINC00942,
PRKDC
a
target
PTBP1.
Functional
showed
markedly
elevated
after
overexpression,
knockdown
reversed
effect.
Mechanistically,
promoted
expression
by
summary,
facilitated
cells
via
binding
promote
expression.
Язык: Английский
Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 25, 2025
The
persistently
high
mortality
rates
associated
with
cancer
underscore
the
imperative
need
for
innovative,
efficacious,
and
safer
therapeutic
agents,
as
well
a
more
nuanced
understanding
of
tumor
biology.
Patient-derived
organoids
(PDOs)
have
emerged
innovative
preclinical
models
significant
translational
potential,
capable
accurately
recapitulating
structural,
functional,
heterogeneous
characteristics
primary
tumors.
When
integrated
cutting-edge
genomic
tools
such
CRISPR,
PDOs
provide
powerful
platform
identifying
driver
genes
novel
targets.
This
comprehensive
review
delves
into
recent
advancements
in
CRISPR-mediated
functional
screens
leveraging
across
diverse
types,
highlighting
their
pivotal
role
high-throughput
genomics
microenvironment
(TME)
modeling.
Furthermore,
this
highlights
synergistic
potential
integrating
CRISPR
immunotherapy,
focusing
on
uncovering
immune
evasion
mechanisms
improving
efficacy
immunotherapeutic
approaches.
Together,
these
technologies
offer
promise
advancing
precision
oncology.
Язык: Английский
Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies
Pharmaceuticals,
Год журнала:
2025,
Номер
18(4), С. 520 - 520
Опубликована: Апрель 3, 2025
Osteosarcoma
is
recognized
as
the
most
prevalent
primary
bone
malignancy,
primarily
affecting
children
and
adolescents.
It
characterized
by
its
aggressive
behavior
high
metastatic
potential,
which
often
leads
to
poor
patient
outcomes.
Despite
advancements
in
surgical
techniques
chemotherapy
regimens,
prognosis
for
patients
with
osteosarcoma
remains
unsatisfactory,
survival
rates
plateauing
over
past
few
decades.
A
significant
barrier
effective
treatment
development
of
resistance,
complicates
management
disease
contributes
recurrence.
This
review
article
aims
provide
a
comprehensive
overview
recent
therapy,
particularly
overcoming
resistance.
We
begin
discussing
current
standard
modalities,
including
resection
conventional
agents
such
methotrexate,
doxorubicin,
cisplatin.
While
these
approaches
have
been
foundational
managing
osteosarcoma,
they
are
limited
adverse
effects
variability
efficacy
among
patients.
To
address
challenges,
we
explore
novel
pharmacological
strategies
that
aim
enhance
includes
targeted
therapies
focusing
on
specific
molecular
alterations
cells
immunotherapeutic
designed
harness
body’s
immune
system
against
tumors.
Additionally,
innovative
drug
delivery
systems
improve
bioavailability
existing
treatments
while
minimizing
toxicity.
The
also
assesses
mechanisms
underlying
efflux
mechanisms,
altered
metabolism,
enhanced
DNA
repair
pathways.
By
synthesizing
research
findings,
highlight
potential
new
therapeutic
resistance
mechanisms.
Ultimately,
this
seeks
inform
future
directions
clinical
practices,
underscoring
need
continued
innovation
treating
outcomes
rates.
Язык: Английский
A novel perspective on bone tumors: advances in organoid research
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 8, 2025
Bone
tumor
organoids
are
three-dimensional
cell
culture
models
derived
from
patient
tissues
or
cells,
capable
of
highly
replicating
the
growth
patterns
and
interactions
bone
tumors
in
vitro
.
Current
treatments
for
hindered
by
challenges
such
as
drug
resistance,
recurrence,
metastasis.
Organoids
enhance
physiological
relevance
models,
thereby
improving
treatment
precision
overcoming
limitations
current
therapeutic
approaches.
Organoid
technology
has
made
preliminary
applications
research,
including
primary
tumors,
metastatic
marrow-derived
tumors.
This
review
will
explore
establishment
organoids,
summarize
their
prospects
various
diseases,
discuss
integration
with
emerging
technologies.
Additionally,
future
directions
organoid
research
be
discussed.
In
future,
expected
to
promote
further
development
medicine.
Язык: Английский
2β-methoxy-2-deethoxyphantomolin synergistically enhances epirubicin effect against triple-negative breast cancer via targeted inhibition of AKT and HR pathways
Bioorganic Chemistry,
Год журнала:
2025,
Номер
unknown, С. 108453 - 108453
Опубликована: Апрель 1, 2025
Язык: Английский
Mitigation of Cisplatin-Induced Nephrotoxicity and Augmentation of Anticancer Potency via Tea Polyphenol Nanoparticles’ Codelivery of siRNA from CRISPR/Cas9 Screened Targets
ACS Applied Materials & Interfaces,
Год журнала:
2024,
Номер
16(44), С. 59721 - 59737
Опубликована: Окт. 26, 2024
Cisplatin,
a
frontline
chemotherapeutic
agent
against
cancer,
faces
challenges
in
clinical
application
due
to
significant
toxicities
and
suboptimal
efficacy.
Renal
toxicity,
dose-limiting
factor
of
cisplatin,
results
from
multifactorial
processes
including
cisplatin-induced
cellular
pyroptosis,
oxidative
damage,
inflammatory
responses.
Our
findings
reveal
that
Tea
Polyphenols
Nanoparticles
(TPNs)
derived
Epigallocatechin
gallate
(EGCG)
effectively
could
address
these
diverse
mechanisms,
comprehensively
alleviating
nephrotoxicity.
Leveraging
TPNs
as
carriers,
chemical
conjugation
enables
the
encapsulation
tetravalent
cisplatin
prodrug,
extending
its
systemic
half-life,
enhancing
tumor
tissue
accumulation,
while
simultaneously
mitigating
renal
toxicity.
Concurrently,
employing
CRISPR/Cas9
kinase
library,
we
identified
CSNK2A1
target
sensitizing
cells
enabling
specific
siRNA
sequences
augment
susceptibility,
thereby
minimizing
dosage
requirement.
Benefiting
versatile
carrier
properties
codeliver
prodrug
anti-CSNK2A1
siRNA,
developed
codelivery
system,
Pt-TPNs/siRNA.
Pt-TPNs/siRNA
not
only
enhances
anticancer
effects
but
also
mitigates
achieving
efficacy
reducing
Mechanistic
safety
assessments
nanoparticles
were
conducted
at
both
animal
levels,
opening
new
avenues
for
improved
utilization
cisplatin.
Язык: Английский