bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: June 17, 2022
ABSTRACT
Aims
The
goal
of
this
study
was
to
determine
whether
NADPH
oxidase
(NOX)-produced
reactive
oxygen
species
enhances
brain
tumor
growth
glioblastoma
(GBM)
under
hypoxic
conditions
and
during
radiation
treatment.
Results
Exogenous
ROS
promoted
in
gliomasphere
cultures
that
expressed
functional
PTEN,
but
not
tumors
were
PTEN
deficient.
Hypoxia
induced
the
production
endogenous
cytoplasmic
cell
via
activation
NOX.
NOX
resulted
oxidation
downstream
Akt
activation.
Radiation
also
which,
turn,
cellular
protection
could
be
abrogated
by
knockdown
key
component,
p22.
Knockdown
p22
inhibited
enhanced
efficacy
PTEN-expressing
GBM
cells.
Innovation
While
other
studies
have
implicated
function
models,
these
demonstrate
physiological
hypoxia
following
GBM,
two
are
seen
patients.
plays
an
important
role
a
model
system,
PTEN-non-functional
systems
provide
potential,
patient-specific
therapeutic
opportunity.
Conclusions
This
provides
strong
basis
for
pursuing
inhibition
cells
as
possible
adjunct
therapy.
Cell Death and Disease,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: May 3, 2025
Abstract
Therapy-induced
senescence
(TIS)
is
a
major
challenge
in
cancer
therapy
as
senescent
cells
provoke
local
and
systemic
inflammation
might
be
the
cause
of
recurrences.
Elucidation
pathways
leading
to
TIS
utmost
importance
for
establishing
strategies
counteract
this.
Previously
we
have
shown
that
temozolomide
(TMZ),
an
alkylating
drug
used
forefront
glioma
therapy,
causes
majorly
cellular
senescence,
which
triggered
by
primary
damage
O
6
-methylguanine,
activating
mismatch
repair
dependent
ATR/ATM-CHK1/CHK2-p53
response
pathway.
The
downstream
remained
explored.
Here,
show
TMZ-induced
does
not
require
activation
DREAM
complex,
but
bound
on
G2-specific
response.
We
CDK
inhibitor
p21
CIP1
interact
with
CDK4,
CDK1
CDK2
causing
abrogation
B-Myb
FOXM1-signaling
pathway
subsequently
arrest
G2-phase.
induced
G2-arrest
incomplete
DNA
synthesis
can
resumed
endoreduplications.
This
process,
inhibited
CDK4-blocking
palbociclib,
preceded
reactivation
G1/S-specific
E2F1-signaling
due
lack
functional
activation.
These
findings
provide
explanation
polyploidization
giant
cell
phenotype
anticancer
drug-induced
cells.
Incomplete
may
also
explain
observation
downregulation
transient
phenomenon,
goes
along
entrance
into
state.
Cells,
Journal Year:
2023,
Volume and Issue:
12(6), P. 897 - 897
Published: March 15, 2023
As
the
most
malignant
primary
brain
tumor
in
adults,
a
diagnosis
of
glioblastoma
multiforme
(GBM)
continues
to
carry
poor
prognosis.
GBM
is
characterized
by
cytoprotective
homeostatic
processes
such
as
activation
autophagy,
capability
confer
therapeutic
resistance,
evasion
apoptosis,
and
survival
strategy
even
hypoxic
nutrient-deprived
microenvironment.
The
current
gold
standard
therapy,
which
involves
radiotherapy
concomitant
adjuvant
chemotherapy
with
temozolomide
(TMZ),
has
been
game-changer
for
patients
GBM,
relatively
improving
both
overall
(OS)
progression-free
(PFS);
however,
TMZ
now
well-known
upregulate
undesirable
limiting
its
efficacy
induction
apoptosis
cells.
identification
targets
utilizing
bioinformatics-driven
approaches,
advancement
modern
molecular
biology
technologies
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)—CRISPR-associated
protein
(Cas9)
or
CRISPR-Cas9
genome
editing,
usage
microRNA
(miRNA)-mediated
regulation
gene
expression
led
selection
many
novel
new
development
creation
promising
combination
therapies.
This
review
explores
state
advanced
bioinformatics
analysis
genetic
their
utilization
synergistic
context
inhibition
autophagy
controlling
growth
GBM.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(8), P. 1525 - 1525
Published: July 29, 2023
Cellular
redox
status
has
a
crucial
role
in
brain
physiology,
as
well
pathologic
conditions.
Physiologic
senescence,
by
dysregulating
cellular
homeostasis
and
decreasing
antioxidant
defenses,
enhances
the
central
nervous
system’s
susceptibility
to
diseases.
The
reduction
of
free
radical
accumulation
through
lifestyle
changes,
supplementation
antioxidants
prophylactic
therapeutic
approach
increase
health,
are
strongly
suggested.
Bilirubin
is
powerful
endogenous
antioxidant,
with
more
recognized
roles
biomarker
disease
resistance,
predictor
all-cause
mortality,
molecule
that
may
promote
health
adults.
alteration
expression
activity
enzymes
involved
bilirubin
production,
an
altered
blood
level,
often
reported
neurologic
conditions
neurodegenerative
diseases
(together
denoted
NCDs)
aging.
These
changes
predict
or
contribute
both
positively
negatively
Understanding
onset
progression
NCDs
will
be
functional
consider
benefits
vs.
drawbacks
hypothesize
best
strategies
for
its
manipulation
purposes.
Frontiers in Oncology,
Journal Year:
2023,
Volume and Issue:
13
Published: Feb. 8, 2023
Background
Nicotinamide
adenine
dinucleotide
(NAD+)
metabolism
is
involved
in
a
series
of
cancer
pathogenesis
processes,
and
considered
promising
therapeutic
target
for
treatment.
However,
comprehensive
analysis
NAD+
events
on
immune
regulation
survival
has
not
yet
been
conducted.
Here,
we
constructed
prognostic
metabolism-related
gene
signature
(NMRGS)
associated
with
checkpoint
inhibitor
(ICI)
efficacy
glioma.
Methods
40
genes
(NMRGs)
were
obtained
from
the
Reactome
database
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
database.
Glioma
cases
transcriptome
data
clinical
information
Chinese
Genome
Atlas
(CGGA)
The
Cancer
(TCGA).
NMRGS
was
based
calculated
risk
score
using
univariate
analysis,
Kaplan–Meier
multivariate
Cox
regression,
nomogram.
This
verified
training
(CGGA693)
validation
(TCGA
CGGA325)
cohorts.
characteristics,
mutation
profile,
response
to
ICI
therapy
subsequently
analyzed
different
subgroups.
Results
Six
genes,
including
CD38,
nicotinamide
kinase
(NADK),
nicotinate
phosphoribosyltransferase
(NAPRT),
nicotinamide/nicotinic
acid
mononucleotide
adenylyltransferase
3
(NMNAT3),
poly(ADP-Ribose)
polymerase
family
member
6
(PARP6),
9
(PARP9),
ultimately
used
construct
model
glioma
patients.
Patients
NMRGS-high
group
showed
poorer
outcome
than
those
NMRGS-low
group.
area
under
curve
(AUC)
indicated
that
good
potential
prediction.
A
nomogram
improved
accuracy
established
independent
factors
(NMRGS
score,
1p19q
codeletion
status,
WHO
grade).
Furthermore,
patients
more
immunosuppressive
microenvironment,
higher
tumor
burden
(TMB),
human
leucocyte
antigen
(HLA)
expression
therapy.
Conclusions
study
landscape
glioma,
which
can
be
guiding
individualized
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(23), P. 12524 - 12524
Published: Nov. 21, 2024
Glioblastoma
Multiforme
(GBM)
is
the
most
aggressive
primary
tumor
of
Central
Nervous
System
(CNS)
with
a
low
survival
rate.
The
malignancy
GBM
sustained
by
bidirectional
crosstalk
between
cells
and
Tumor
Microenvironment
(TME).
This
mechanism
intercellular
communication
mediated,
at
least
in
part,
release
exosomes.
Glioma-Derived
Exosomes
(GDEs)
work,
indeed,
as
potent
signaling
particles
promoting
progression
brain
tumors
inducing
proliferation,
invasion,
migration,
angiogenesis
resistance
to
chemotherapy
or
radiation.
Given
their
nanoscale
size,
exosomes
can
cross
blood-brain
barrier
(BBB),
thus
becoming
not
only
promising
biomarker
predict
diagnosis
prognosis
but
also
therapeutic
target
treat
GBM.
In
this
review,
we
describe
structural
functional
characteristics
involvement
development,
diagnosis,
treatment.
addition,
discuss
how
be
modified
used
target/drug
delivery
system
for
clinical
applications.
Journal of Clinical Medicine,
Journal Year:
2023,
Volume and Issue:
12(10), P. 3430 - 3430
Published: May 12, 2023
Glioblastomas
(GBM)
are
a
devastating
disease
with
extremely
poor
clinical
outcomes.
Resident
(microglia)
and
infiltrating
macrophages
substantial
component
of
the
tumor
environment.
In
GBM
other
cancers,
tumor-derived
extracellular
vesicles
(EVs)
suppress
macrophage
inflammatory
responses,
impairing
their
ability
to
identify
phagocytose
cancerous
tissues.
Furthermore,
these
then
begin
produce
EVs
that
support
growth
migration.
This
cross-talk
between
macrophages/microglia
gliomas
is
significant
contributor
pathophysiology.
Here,
we
review
mechanisms
through
which
GBM-derived
impair
function,
how
subsequent
macrophage-derived
growth,
current
therapeutic
approaches
target
GBM/macrophage
EV
crosstalk.
Antioxidants and Redox Signaling,
Journal Year:
2023,
Volume and Issue:
39(13-15), P. 890 - 903
Published: July 20, 2023
Aims:
The
goal
of
this
study
was
to
determine
whether
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
oxidase
(NOX)-produced
reactive
oxygen
species
(ROS)
enhance
brain
tumor
growth
glioblastoma
(GBM)
under
hypoxic
conditions
and
during
radiation
treatment.
Results:
Exogenous
ROS
promoted
in
gliomasphere
cultures
that
expressed
functional
tensin
homolog
(PTEN),
but
not
tumors
were
PTEN
deficient.
Hypoxia
induced
the
production
endogenous
cytoplasmic
cell
via
activation
NOX.
NOX
resulted
oxidation
downstream
protein
kinase
B
(Akt)
activation.
Radiation
also
NOX,
which,
turn,
cellular
protection
could
be
abrogated
by
knockdown
key
component,
p22.
Knockdown
p22
inhibited
enhanced
efficacy
PTEN-expressing
GBM
cells.
Innovation:
While
other
studies
have
implicated
function
models,
demonstrates
physiological
hypoxia
following
GBM,
two
are
seen
patients.
plays
an
important
role
a
model
system,
PTEN-nonfunctional
systems,
provides
potential,
patient-specific
therapeutic
opportunity.
Conclusion:
This
strong
basis
for
pursuing
inhibition
cells
as
possible
adjunct
therapy.
Antioxid.
Redox
Signal.
39,
890–903.
