International Journal of Frontiers in Medicine,
Journal Year:
2023,
Volume and Issue:
5(11)
Published: Jan. 1, 2023
Although
the
target
of
KRAS
G12C
is
no
longer
unbreakable,
resistance
to
current
drugs
against
occurs.
The
emergence
a
new
drug,
VT204,
expected
be
clinical
drug
in
this
field.
Preclinical
pharmacokinetic
(PK)
studies
animal
models
during
formulation
development
phase
provide
preliminary
evidence
PK
behaviour
before
humans
and
help
tailor
dosage
form
necessary
behaviour.
A
high-performance
liquid
chromatography-tandem
mass
spectrometry
(LC-MS/MS)
method
was
developed
determine
VT204
rat
plasma.
single
chromatographic
run
performed
on
ZORBAX
Eclipse
Plus
C18
(2.1
mm×50
mm,
3.5
μm,
Agilent)
at
flow
rate
0.75
mL·min-1.
intra-
inter-batch
accuracies
ranged
from
95.3%
103.3%,
precision
did
not
exceed
15%.
t1/2
intravenous
oral
administration
rats
1.09±0.05
h
1.47±0.55
h,
which
resulted
bioavailability
63.52%.
This
accurate
specific
provides
good
solution
for
study
rats.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(11), P. 9437 - 9437
Published: May 29, 2023
Non-small
cell
lung
cancer
(NSCLC)
is
a
fatal
malignant
tumor
with
high
mortality
rate.
Cancer
stem
cells
(CSCs)
play
pivotal
roles
in
initiation
and
progression,
treatment
resistance,
NSCLC
recurrence.
Therefore,
the
development
of
novel
therapeutic
targets
anticancer
drugs
that
effectively
block
CSC
growth
may
improve
outcomes
patients
NSCLC.
In
this
study,
we
evaluated,
for
first
time,
effects
natural
cyclophilin
A
(CypA)
inhibitors,
including
23-demethyl
8,13-deoxynargenicin
(C9)
cyclosporin
(CsA),
on
CSCs.
C9
CsA
more
sensitively
inhibited
proliferation
epidermal
factor
receptor
(EGFR)-mutant
CSCs
than
EGFR
wild-type
Both
compounds
suppressed
self-renewal
ability
NSCLC-CSC-derived
vivo.
Furthermore,
by
activating
intrinsic
apoptotic
pathway.
Notably,
reduced
expression
levels
major
markers,
integrin
α6,
CD133,
CD44,
ALDH1A1,
Nanog,
Oct4,
Sox2,
through
dual
downregulation
CypA/CD147
axis
activity
Our
results
also
show
tyrosine
kinase
inhibitor
afatinib
inactivated
decreased
CypA
CD147
CSCs,
suggesting
close
crosstalk
between
pathways
regulating
growth.
addition,
combined
or
potently
EGFR-mutant
single-compound
treatments.
These
findings
suggest
inhibitors
are
potential
agents
suppress
either
as
monotherapy
combination
afatinib,
interfering
EGFR.
Molecular Medicine Reports,
Journal Year:
2024,
Volume and Issue:
31(1)
Published: Oct. 30, 2024
Gastric
cancer
stem
cells
(GCSCs)
contribute
to
the
challenging
aspects
of
gastric
cancer,
such
as
progression,
metastasis,
treatment
resistance
and
recurrence.
Inhibitors
targeting
cyclophilin
A
(CypA)
have
shown
potential
in
curtailing
GCSC
growth.
Building
upon
this,
current
study
delved
deeper
into
understanding
functional
role
CypA
controlling
proliferation
metastatic
capabilities
GCSCs,
employing
CypA‑specific
small
interfering
RNA.
The
results
revealed
that
knockdown
led
significant
suppression
growth
tumorsphere‑forming
capacity
GCSCs
derived
from
AGS
cells.
This
effect
was
mediated
by
arresting
cell
cycle
at
G0/G1
S
phases,
promoting
apoptosis.
Furthermore,
silencing
exerted
inhibitory
effects
on
migration
invasion
modulating
process
epithelial‑mesenchymal
transition.
Notably,
observed
antiproliferative
antimetastatic
were
associated
with
downregulation
critical
regulators
stemness,
CD44,
CD133,
aldehyde
dehydrogenase
1
family
member
A1,
NANOG,
OCT4
SOX2.
regulation
occurred
through
inactivation
CD147/STAT3/AKT/ERK
signaling
pathway.
Additionally,
effectively
curbed
in
vivo
tumor
a
chorioallantoic
membrane
assay
using
chick
embryos.
These
findings
underscore
metastasis
highlighting
its
an
effective
therapeutic
target
for
eradicating
improving
outcomes.
Cells,
Journal Year:
2023,
Volume and Issue:
13(1), P. 22 - 22
Published: Dec. 21, 2023
Liver
cancer
stem
cells
(LCSCs)
contribute
to
the
initiation,
metastasis,
treatment
resistance,
and
recurrence
of
hepatocellular
carcinoma
(HCC).
Therefore,
exploring
potential
anticancer
agents
targeting
LCSCs
may
offer
new
therapeutic
options
overcome
HCC
failure.
Hovenia
dulcis
Thunberg
(HDT),
a
tree
from
buckthorn
family
found
in
Asia,
exhibits
various
biological
activities,
including
antifatigue,
antidiabetic,
neuroprotective,
hepatoprotective,
antitumor
activities.
However,
effect
HDT
eliminating
remains
be
confirmed.
In
this
study,
we
evaluated
inhibitory
activity
ethanol,
chloroform,
ethyl
acetate
extracts
branches
on
growth
Huh7-derived
LCSCs.
The
extract
(EAHDT)
exhibited
most
potent
against
Huh7
among
three
extracts.
EAHDT
suppressed
vitro
self-renewal
ability
reduced
tumor
vivo
using
LCSC-transplanted
chick
embryo
chorioallantoic
membrane
model.
Furthermore,
not
only
arrested
cell
cycle
G0/G1
phase
but
also
induced
receptor-interacting
protein
kinase
3/mixed-lineage
domain-like
protein-mediated
necroptosis
caspase-dependent
apoptosis
concentration-dependent
manner.
was
associated
with
downregulation
c-MET-mediated
downstream
signaling
pathways
key
stemness
markers.
Based
these
findings,
propose
that
can
used
as
natural
drug
candidate
prevent
treat
by
eradicating
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 19, 2024
Abstract
Background
The
intricate
interplay
between
stemness
markers
and
cell
death
pathways
significantly
influences
the
pathophysiology
of
cervical
cancer.
SOX2,
a
pivotal
regulator
stem
pluripotency,
has
recently
been
implicated
in
modulation
ferroptosis,
specialized
form
iron-dependent
death,
cancer
dynamics.
This
study
delineates
role
SOX2
ferroptotic
landscape
carcinoma.
Objective
To
delineate
association
expression
ferroptosis
develop
robust,
SOX2-centric
predictive
model
for
patient
prognosis,
enhancing
personalized
therapeutic
approaches.
Methods
A
multi-dimensional
approach
integrating
advanced
bioinformatics,
comprehensive
molecular
profiling,
state-of-the-art
machine
learning
algorithms
was
employed
to
assess
patterns
their
correlation
with
tissues.
prognostic
meticulously
crafted,
incorporating
levels
indicators.
Results
investigation
unveiled
profound
processes
cancer,
substantiated
by
robust
evidence.
developed
model,
underpinned
expression,
exhibited
superior
accuracy
potentially
guiding
decision-making.
Conclusion
underscores
critical
orchestrating
pathway
presenting
novel
framework.
emerges
as
significant
advancement
evaluation,
offering
gateway
precision
oncology
realm
gynecologic
oncology.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(23), P. 12909 - 12909
Published: Nov. 30, 2024
Gastric
cancer
(GC)
ranks
as
the
fifth
most
prevalent
globally.
Owing
to
absence
of
early
manifest
symptoms,
it
is
difficult
diagnose
GC
until
has
metastasized
other
organs.
Hence,
prevention
and
treatment
have
become
major
concerns
for
patients.
International Journal of Frontiers in Medicine,
Journal Year:
2023,
Volume and Issue:
5(11)
Published: Jan. 1, 2023
Although
the
target
of
KRAS
G12C
is
no
longer
unbreakable,
resistance
to
current
drugs
against
occurs.
The
emergence
a
new
drug,
VT204,
expected
be
clinical
drug
in
this
field.
Preclinical
pharmacokinetic
(PK)
studies
animal
models
during
formulation
development
phase
provide
preliminary
evidence
PK
behaviour
before
humans
and
help
tailor
dosage
form
necessary
behaviour.
A
high-performance
liquid
chromatography-tandem
mass
spectrometry
(LC-MS/MS)
method
was
developed
determine
VT204
rat
plasma.
single
chromatographic
run
performed
on
ZORBAX
Eclipse
Plus
C18
(2.1
mm×50
mm,
3.5
μm,
Agilent)
at
flow
rate
0.75
mL·min-1.
intra-
inter-batch
accuracies
ranged
from
95.3%
103.3%,
precision
did
not
exceed
15%.
t1/2
intravenous
oral
administration
rats
1.09±0.05
h
1.47±0.55
h,
which
resulted
bioavailability
63.52%.
This
accurate
specific
provides
good
solution
for
study
rats.
