bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 23, 2025
Abstract
Lung
cancer
is
the
leading
cause
of
cancer-related
mortality
worldwide.
Non-small
cell
lung
(NSCLC)
most
common
subtype
and
comprises
85%
cases.
Despite
treatment
advances,
local
control
after
curative-intent
chemoradiation
for
NSCLC
remains
suboptimal.
Polo-like
kinase
4
(PLK4)
a
serine-threonine
that
plays
critical
role
in
regulation
centrosome
duplication
cycle
progression
overexpressed
NSCLC,
thus,
making
it
potential
therapeutic
target.
CFI-400945
an
orally
available
PLK4
inhibitor
currently
undergoing
clinical
trial
evaluation.
As
radiation
causes
death
primarily
by
mitotic
catastrophe,
process
enhanced
alterations
amplification,
we
hypothesized
disruption
machinery
inhibition
would
enhance
effects
NSCLC.
resulted
radiosensitization
lines.
In
contrast,
had
no
effect
on
radiosensitivity
normal
fibroblasts.
did
not
affect
cell-cycle
phase
distribution
prior
to
radiation,
but
rather
combination
increased
G2/M
arrest,
concomitant
increase
through
catastrophe.
Lastly,
radiation-induced
tumor
growth
delay
xenografts.
These
data
indicate
targeting
novel
approach
sensitivity
vitro
vivo
potentiation
amplification
Pharmaceutics,
Год журнала:
2023,
Номер
15(1), С. 236 - 236
Опубликована: Янв. 10, 2023
Despite
significant
advances
in
cancer
therapy
over
the
years,
its
complex
pathological
process
still
represents
a
major
health
challenge
when
seeking
effective
treatment
and
improved
healthcare.
With
advent
of
nanotechnologies,
nanomedicine-based
has
been
widely
explored
as
promising
technology
able
to
handle
requirements
clinical
sector.
Superparamagnetic
iron
oxide
nanoparticles
(SPION)
have
at
forefront
nanotechnology
development
since
mid-1990s,
thanks
their
former
role
contrast
agents
for
magnetic
resonance
imaging.
Though
use
MRI
probes
discontinued
due
an
unfavorable
cost/benefit
ratio,
several
innovative
applications
therapeutic
tools
prompted
renewal
interest.
The
unique
characteristics
SPION,
i.e.,
properties
enabling
specific
response
submitted
high
frequency
(magnetic
hyperthermia)
or
low
(magneto-mechanical
therapy)
alternating
field,
ability
generate
reactive
oxygen
species
(either
intrinsically
activated
using
various
stimuli),
make
them
particularly
adapted
therapy.
This
review
provides
comprehensive
description
fundamental
aspects
SPION
formulation
highlights
recent
approaches
regarding
vivo
field
At
present,
radiotherapy
(RT)
still
acquires
limited
success
in
clinical
due
to
the
lessened
DNA
damage
under
hypoxia
and
acquired
immune
tolerance
owing
amplified
programmed
death
ligand-1
(PD-L1)
expression.
Incredibly,
intracellular
PD-L1
expression
depression
is
proven
better
sensitize
RT
by
inhibiting
repair.
However,
disability
of
clinically
used
antibodies
disrupting
extracellular
PD-L1function
limits
effectiveness
radio-immunotherapy.
Therefore,
regulation
strategies
are
urgently
needed
Hence,
for
this
purpose,
TPP-LND
synthesized
linking
mitochondrial-targeted
triphenylphosphine
cations
(TPP+
)
antineoplastic
agent
lonidamine
(LND),
which
significantly
reduces
dose
LND
induce
effective
oxidative
phosphorylation
inhibition
(2
vs
300
µM).
Then,
wrapped
with
liposomes
form
TPP-LND@Lip
nanoparticles.
By
doing
this,
nanoparticles
can
reversing
hypoxic
microenvironment
tumors
generate
more
reducing
via
enhancing
adenosine
5'-monophosphate-activated
protein
kinase
activation.
As
expected,
these
well-designed
economical
than
conventional
anti-PD-L1
some
extent.
Frontiers in Oncology,
Год журнала:
2021,
Номер
11
Опубликована: Июль 8, 2021
Lung
cancer
is
the
leading
cause
of
cancer-related
mortality
for
males
and
females.
Radiation
therapy
(RT)
one
primary
treatment
modalities
lung
cancer.
While
delivering
prescribed
dose
to
tumor
targets,
it
essential
spare
tissues
near
targets—the
so-called
organs-at-risk
(OARs).
An
optimal
RT
planning
benefits
from
accurate
segmentation
gross
volume
surrounding
OARs.
Manual
a
time-consuming
tedious
task
radiation
oncologists.
Therefore,
crucial
develop
automatic
image
relieve
oncologists
contouring
work.
Currently,
atlas-based
technique
commonly
used
in
clinical
routines.
However,
this
depends
heavily
on
similarity
between
atlas
segmented.
With
significant
advances
made
computer
vision,
deep
learning
as
part
artificial
intelligence
attracts
increasing
attention
medical
segmentation.
In
article,
we
reviewed
based
techniques
related
compared
them
with
technique.
At
present,
auto-segmentation
OARs
relatively
large
such
heart
etc.
outperforms
organs
small
esophagus.
The
average
Dice
coefficient
(DSC)
lung,
liver
are
over
0.9,
best
DSC
spinal
cord
reaches
0.9.
esophagus
ranges
0.71
0.87
ragged
performance.
terms
volume,
below
0.8.
Although
indicate
superiority
many
aspects
manual
segmentation,
various
issues
still
need
be
solved.
We
discussed
potential
including
low
contrast,
dataset
size,
consensus
guidelines,
network
design.
Clinical
limitations
future
research
directions
were
well.
Journal of Medicinal Chemistry,
Год журнала:
2022,
Номер
65(13), С. 9447 - 9458
Опубликована: Июль 4, 2022
To
overcome
the
resistance
of
nonsmall
cell
lung
cancer
(NSCLC)
cells
to
cisplatin
and
inhibit
their
metastasis,
we
proposed
develop
a
Cu(II)
agent
based
on
specific
residue(s)
HSA
nanoparticles
(NPs)
for
multitargeting
tumor
microenvironment
(TME).
this
end,
not
only
synthesized
four
2-hydroxy-3-methoxybenzaldehyde
thiosemicarbazone
compounds
(C1–C4),
obtaining
Cu
compound
(C4)
with
significant
cytotoxicity
by
studying
structure–activity
relationships,
but
also
revealed
binding
mechanism
C4
through
X-ray
crystallography
confirmed
successful
construction
new
HSA-C4
NPs
delivery
system.
inhibited
A549cisR
growth
optimized
anticancer
behavior
C4.
We
further
C4/HSA-C4
NP
TME
resistance:
killing
acting
mtDNA
inducing
apoptosis,
polarizing
M2-type
macrophages
M1-type,
inhibiting
angiogenesis.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
173, С. 116445 - 116445
Опубликована: Март 18, 2024
Dasatinib-related
resistance
frequently
occurs
and
may
lead
to
the
failure
of
chemotherapy;
thus,
dose
interruptions
are
necessary.
Cannabidiol
(CBD)
has
potential
for
integration
with
orthodox
cancer
care.
In
this
study,
we
explored
combination
effect
CBD
dasatinib
on
A549
cells.
in
could
induce
significant
synergistic
apoptosis
vitro
(ZIP
>
10)
vivo.
The
low-dose
exhibited
antiproliferative
proapoptotic
effects
through
up-regulation
caspase-3
Bax,
down-regulation
Bcl-2
xenograft
mouse
model
suggested
that
was
more
efficient
safer.
short,
a
anticancer
by
targeting
SRC/PI3K/AKT
signaling
pathway,
suggesting
therapeutic
option
treatment
lung
cancer.
ACS Biomaterials Science & Engineering,
Год журнала:
2020,
Номер
6(6), С. 3550 - 3562
Опубликована: Апрель 29, 2020
Radiotherapy
(RT)
is
a
major
treatment
method
for
non-small-cell
lung
cancer
(NSCLC),
and
development
of
new
modality
now
critical
to
amplify
the
negative
effects
RT
on
tumors.
In
this
study,
we
demonstrated
nanoparticle-loaded
block
copolymer
micellar
system
hyperthermia
(HT)
that
can
be
used
synergistic
therapy
under
alternating
magnetic
field
(AMF)
radiation
field.
Block
micelles
(polyethylene
glycol-block-polycaprolactone,
or
PEG-PCL)
containing
hyaluronic
acid
(HA)
Mn–Zn
ferrite
nanoparticles
(MZF)
were
fabricated
via
two-step
preparation.
HA-modified
(MZF-HA)
enriched
in
CD44
highly
expressing
tumor
cells,
such
as
A549
(human
adenocarcinoma
cell
line),
through
an
active
targeting
mechanism
receptor–ligand
binding
HA
(HA
receptor).
MZF
generate
thermal
energy
AMF,
leading
local
temperature
increase
approximately
43
°C
at
sites
mild
HT,
increased
oxygenation
enhance
therapeutic
effect
RT.
vitro
experiments
show
MZF-HA
able
achieve
excellent
specific
performance
toward
cells
with
biocompatibility
well
enhanced
HT
by
apoptosis
flow
cytometry.
subcutaneous
xenografts
model,
MRI
confirms
enrichment
tumor,
hypoxia
immunohistochemistry
analysis
(IHC)
proved
after
HT.
Furthermore,
volume
decreases
49.6%
combination
comparison
58.8%
untreated
group.
These
results
suggest
application
further
clinical
NSCLC
evaluation.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2020,
Номер
39(1)
Опубликована: Ноя. 23, 2020
Abstract
Accumulating
evidence
suggests
that
radiation
treatment
causes
an
adaptive
response
of
lung
adenocarcinoma
(LUAD),
which
in
turn
attenuates
the
lethal
effect
irradiation.
Previous
microarray
assays
manifested
change
gene
expression
profile
after
Bioinformatics
analysis
significantly
changed
genes
revealed
VANGL1
may
notably
influence
on
LUAD.
To
determine
role
VANGL1,
this
study
knocked
down
or
overexpressed
M6A
level
mRNA
was
determined
by
M6A-IP-qPCR
assay.
Irradiation
caused
up-regulation
with
increase
m6A
level.
Depletion
readers,
IGF2BP2/3,
undermined
stability
and
upon
miR-29b-3p
decreased
irradiation,
however
is
a
target
identified
Luciferase
report
The
reduction
inhibited
degradation
mRNA.
Knockdown
enhanced
detrimental
irradiation
LUAD,
as
indicated
more
severe
DNA
damage
increased
percentage
apoptotic
cells.
Immunocoprecipitation
interaction
between
BRAF.
BRAF
probably
through
suppressing
protein
degradation,
led
to
downstream
effectors,
TP53BP1
RAD51.
These
effectors
are
involved
repair
damage.
In
summary,
which,
turn,
mitigated
LUAD
protecting
from
activating
BRAF/TP53BP1/RAD51
cascades.
Increased
reduced
took
responsibility
overexpression
Critical Reviews in Oncology/Hematology,
Год журнала:
2024,
Номер
196, С. 104284 - 104284
Опубликована: Фев. 2, 2024
Non-small
cell
lung
cancer
(NSCLC)
remains
one
of
the
leading
causes
cancer-related
deaths
worldwide.
Different
treatment
approaches
are
typically
employed
based
on
stage
NSCLC.
Common
clinical
methods
include
surgical
resection,
drug
therapy,
and
radiation
therapy.
However,
with
introduction
utilization
immune
checkpoint
inhibitors,
has
entered
a
new
era,
completely
revolutionizing
landscape
for
various
cancers
significantly
improving
overall
patient
survival.
Concurrently,
resistance
often
poses
critical
challenge,
many
patients
experiencing
disease
progression
following
an
initial
response
due
to
resistance.
Increasing
evidence
suggests
that
tumor
microenvironment
(TME)
plays
pivotal
role
in
Tumor-associated
macrophages
(TAMs)
within
TME
can
promote
NSCLC
by
secreting
cytokines
activating
signaling
pathways,
interacting
other
cells.
Therefore,
this
article
will
focus
elucidating
key
mechanisms
TAMs
analyze
how
targeting
reduce
levels
NSCLC,
providing
comprehensive
understanding
principles
overcome