Anti-Cancer Agents in Medicinal Chemistry,
Год журнала:
2024,
Номер
24(19), С. 1431 - 1441
Опубликована: Авг. 12, 2024
Introduction:
Sorafenib
(Sor)
is
the
first-line
treatment
option
in
clinics
for
treating
advanced
unresectable
hepatocellular
carcinoma
(HCC).
However,
acquired
chemoresistance
and
adverse
side
effects
associated
with
Sor
monotherapy
limit
its
clinical
benefits.
We
have
previously
reported
exceptional
anti-HCC
potential
of
uttroside
B
(Utt-B),
a
furostanol
saponin
isolated
our
lab
from
Solanum
nigrum
Linn.
leaves.
The
current
study
has
evaluated
supremacy
combinatorial
regimen
Utt-B
over
monotherapy.
Methods:
MTT
assay
was
used
In
vitro
cytotoxicity
studies.
A
clonogenic
conducted
to
assess
anti-proliferative
effect
combination.
Annexin
V/PI
staining,
confocal
microscopy,
FACS
cell
cycle
analysis,
Western
blotting
experiments
were
performed
validate
pro-apoptotic
combination
HepG2
Huh7
lines.
Pharmacological
safety
evaluation
Swiss
albino
mice.
Results:
Our
results
indicate
that
augments
Sor-induced
cells.
inhibits
proliferation
liver
cancer
cells
by
inducing
apoptosis
through
activation
caspases
7
3,
leading
PARP
cleavage.
Furthermore,
does
not
induce
any
acute
toxicity
vivo,
even
at
dose
five
times
effective
therapeutic
dose.
Conclusion:
highlight
as
an
chemosensitizer,
which
can
augment
efficacy
against
HCC
circumvent
toxic
effects.
Moreover,
this
first
only
report
date
on
chemosensitizing
demonstrates
pharmacological
novel
involving
combating
HCC.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Апрель 15, 2024
Abstract
Cancer
is
a
major
public
health
problem
worldwide
with
more
than
an
estimated
19.3
million
new
cases
in
2020.
The
occurrence
rises
dramatically
age,
and
the
overall
risk
accumulation
combined
tendency
for
cellular
repair
mechanisms
to
be
less
effective
older
individuals.
Conventional
cancer
treatments,
such
as
radiotherapy,
surgery,
chemotherapy,
have
been
used
decades
combat
cancer.
However,
emergence
of
novel
fields
research
has
led
exploration
innovative
treatment
approaches
focused
on
immunotherapy,
epigenetic
therapy,
targeted
multi-omics,
also
multi-target
therapy.
hypothesis
was
based
that
drugs
designed
act
against
individual
targets
cannot
usually
battle
multigenic
diseases
like
Multi-target
therapies,
either
combination
or
sequential
order,
recommended
acquired
intrinsic
resistance
anti-cancer
treatments.
Several
studies
multi-targeting
treatments
due
their
advantages
include;
overcoming
clonal
heterogeneity,
lower
multi-drug
(MDR),
decreased
drug
toxicity,
thereby
side
effects.
In
this
study,
we'll
discuss
about
drugs,
benefits
improving
recent
advances
field
multi-targeted
drugs.
Also,
we
will
study
performed
clinical
trials
using
therapeutic
agents
treatment.
iScience,
Год журнала:
2024,
Номер
27(6), С. 109893 - 109893
Опубликована: Май 3, 2024
Recent
advances
in
cancer
research
have
unveiled
a
significant
yet
previously
underappreciated
aspect
of
oncology:
the
presence
and
role
intratumoral
microbiota.
These
microbial
residents,
encompassing
bacteria,
fungi,
viruses
within
tumor
tissues,
been
found
to
exert
considerable
influence
on
development,
progression,
efficacy
therapeutic
interventions.
This
review
aims
synthesize
these
groundbreaking
discoveries,
providing
an
integrated
overview
identification,
characterization,
functional
roles
microbiota
biology.
We
focus
elucidating
complex
interactions
between
microorganisms
microenvironment,
highlighting
their
potential
as
novel
biomarkers
targets.
The
purpose
this
is
offer
comprehensive
understanding
dimension
cancer,
paving
way
for
innovative
approaches
diagnosis
treatment.
Pharmacological Research,
Год журнала:
2024,
Номер
203, С. 107142 - 107142
Опубликована: Март 24, 2024
ZLDI-8
is
an
A
disintegrin
and
metalloproteinase
domain
17
(ADAM17)
inhibitor
that
suppresses
the
shedding
of
Notch1
to
intracellular
(NICD).
In
previous
studies,
we
found
was
able
sensitize
HCC
sorafenib,
but
mechanism
action
remains
unclear.
The
sensitizing
effects
were
tested
both
in
vitro
vivo.
EMT-related
factors,
sorafenib
sensitivity-related
proteins
ECM-related
gene
expression
assessed
using
immunohistochemistry,
RTPCR
Western
blotting.
Knockdown
assays
conducted
determine
relationship
between
Notch
Integrin
pathways.
CoIP
assays,
nuclear
cytoplasmic
fractionation
immunofluorescence
colocalization
applied
explore
interaction
Appropriate
statistical
analysis
methods
used
assess
significance
experimental
results
ensure
scientific
validity
reliability
design.
We
ECM-
downregulated
after
treatment
(P<0.05).
significantly
Integrinβ1
Integrinβ3
vivo
(P<0.05),
possibly
through
Foxc2-dependent
regulation.
Mechanistically,
interfering
with
Integrin-linked
kinase
(ILK)
NICD
may
downregulate
targeted
by
thereby
cells
sorafenib.
retroregulation
Integrinβ
ILK
occur
be
result
translocation
complexus.
Our
study
indicates
blocking
pathway
affect
crosstalk
Integrinβ/ILK
signaling
pathways,
thus
providing
a
potential
therapeutic
strategy
for
HCC.
Biomolecules,
Год журнала:
2024,
Номер
14(2), С. 218 - 218
Опубликована: Фев. 12, 2024
Considering
the
pivotal
role
of
angiogenesis
in
solid
tumor
progression,
we
developed
a
novel
series
quinazoline–thiazole
hybrids
(SA01–SA07)
as
antiproliferative
and
anti-angiogenic
agents.
Four
out
seven
compounds
displayed
superior
activity
(IC50
=1.83-4.24
µM)
on
HepG2
cells
compared
to
sorafenib
=
6.28
µM).
The
affinity
towards
VEGFR2
kinase
domain
was
assessed
through
silico
prediction
by
molecular
docking,
dynamics
studies,
MM-PBSA.
high
degree
similarity
regarding
binding
pose
within
active
site
VEGFR2,
with
different
orientation
4-substituted-thiazole
moieties
allosteric
pocket.
Molecular
MM-PBSA
evaluations
identified
SA05
hybrid
forming
most
stable
complex
sorafenib.
impact
vascular
cell
proliferation
EA.hy926
cells.
Six
(SA01–SA05,
SA07)
anti-proliferative
0.79–5.85
6.62
toxicity
evaluated
BJ
Further
studies
effect
promising
compounds,
SA04
SA05,
assessment
EA.hy296
motility
using
wound
healing
assay
ovo
potential
CAM
sorafenib,
led
confirmation
potential.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 18, 2023
Previous
studies
have
demonstrated
that
PANoptosis
is
strongly
correlated
with
cancer
immunity
and
progression.
This
study
aimed
to
develop
a
PANoptosis-related
signature
(PANRS)
explore
its
potential
value
in
predicting
the
prognosis
immunotherapy
response
of
hepatocellular
carcinoma
(HCC).Based
on
expression
genes,
three
molecular
subtypes
were
identified.
To
construct
signature,
differentially
expressed
genes
between
different
subjected
multivariate
least
absolute
shrinkage
selection
operator
Cox
regression
analyses.
The
risk
scores
patients
training
set
calculated
using
signature.
classified
into
high-risk
low-risk
groups
based
median
scores.
predictive
performance
was
evaluated
Kaplan-Meier
plotter,
receiving
operating
characteristic
curves,
nomogram,
calibration
curve.
results
validated
external
datasets.
Additionally,
correlation
immune
landscape
drug
sensitivity
examined.
Furthermore,
effect
LPCAT1
knockdown
HCC
cell
behavior
verified
vitro
experiments.This
developed
PANRS.
score
obtained
by
PANRS
an
independent
factor
for
exhibited
good
prognostic
performance.
nomogram
constructed
clinical
information
can
accurately
predicted
survival
probability
HCC.
Patients
high
tend
generate
immunosuppressive
microenvironment.
They
also
favorable
immunotherapy,
as
evidenced
tumor
mutational
burden,
checkpoint
gene
expression,
human
leukocyte
antigen
low
dysfunction
exclusion
enabled
identification
15
chemotherapeutic
agents,
including
sorafenib,
levels,
guiding
treatment.
upregulated
lines.
markedly
decreased
proliferation
migration.PANRS
predict
consequently
guide
individualized
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
179, С. 117343 - 117343
Опубликована: Авг. 24, 2024
BACKGROUND
AND
AIMS:
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
common
malignancies
in
world
and
sixth
leading
cause
cancer
death
worldwide,
it
urgent
to
find
safe
effective
drugs
for
treatment.
As
an
important
therapeutic
method,
small-molecule
are
continually
being
updated
achieve
improved
effects.
The
purpose
this
study
was
investigate
structural
effects
various
FDA-listed
sorafenib,
cabozantinib,
lenvatinib,
regorafenib
on
corresponding
HCC
targets
possible
optimization
methods,
explore
mechanism
identifying
potential
that
offer
better
efficacy
fewer
side
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
Hepatocellular
carcinoma
(HCC),
one
of
the
most
lethal
cancers
liver,
has
limited
treatment
options
at
advanced
stages.
Here,
bismuth
gadolinium
(BiGd)
nanoparticles
(NPs)
conjugated
with
anti-vascular
endothelial
growth
factor
antibody
(aVEGF)
are
designed
and
tested
for
targeted
image-guided
radiation
therapy
against
HCC.
The
BiGd
NPs
synthesized
using
sol-gel
technique,
functionalized
silica
NPs,
labeled
fluorescent
protamine-rhodamine
B.
For
tumor
targeting,
aVEGF,
an
in
vitro
study
confirms
binding
aVEGF-BiGd
nanoconjugate
to
McA-RH7777
hepatoma
cells.
Biocompatibility
is
evaluated
cells,
no
cytotoxicity
observed
even
250
μg/mL.
Also,
demonstrates
vivo
microcomputed
tomography
contrast
enhancement.
and/or
(RT)
conducted
female
BALB/c
nude
mice
subcutaneously
implanted
a
significant
reduction
size
treated
RT
compared
other
groups
(p
<
0.01).
combined
effect
exhibits
decreased
vascularity,
cell
proliferation,
increased
apoptosis.
This
potential
developed
hybrid
radiotherapy
