Biomedicines,
Год журнала:
2017,
Номер
5(2), С. 29 - 29
Опубликована: Июнь 9, 2017
Nuclear
factor-κB
(NF-κB)
is
a
transcription
factor
regulating
wide
array
of
genes
mediating
numerous
cellular
processes
such
as
proliferation,
differentiation,
motility
and
survival,
to
name
few.
Aberrant
activation
NF-κB
frequent
event
in
cancers,
including
glioblastoma,
the
most
common
lethal
form
brain
tumours
glial
cell
origin
(collectively
termed
gliomas).
Glioblastoma
characterized
by
high
heterogeneity,
resistance
therapy
almost
inevitable
recurrence
after
surgery
treatment.
aberrantly
activated
response
variety
stimuli
where
its
activity
has
been
implicated
ranging
from
maintenance
cancer
stem-like
cells,
stimulation
invasion,
promotion
mesenchymal
identity,
radiotherapy.
This
review
examines
mechanisms
involvement
several
underlying
glioblastoma
propagation,
discusses
some
important
questions
future
research
into
roles
glioblastoma.
International Journal of Molecular Sciences,
Год журнала:
2019,
Номер
20(3), С. 755 - 755
Опубликована: Фев. 11, 2019
The
mammalian
or
mechanistic
target
of
rapamycin
(mTOR)
pathway
plays
a
crucial
role
in
regulation
cell
survival,
metabolism,
growth
and
protein
synthesis
response
to
upstream
signals
both
normal
physiological
pathological
conditions,
especially
cancer.
Aberrant
mTOR
signaling
resulting
from
genetic
alterations
different
levels
the
signal
cascade
is
commonly
observed
various
types
cancers.
Upon
hyperactivation,
promotes
proliferation
metabolism
that
contribute
tumor
initiation
progression.
In
addition,
also
negatively
regulates
autophagy
via
ways.
We
discuss
its
key
downstream
factors,
specific
changes
inhibitors
applied
as
therapeutic
strategies
eight
solid
tumors.
Although
monotherapy
combination
therapy
with
have
been
extensively
preclinical
clinical
trials
cancer
types,
innovative
therapies
better
efficacy
less
drug
resistance
are
still
great
need,
new
biomarkers
deep
sequencing
technologies
will
facilitate
these
targeting
drugs
benefit
patients
personalized
therapy.
BioMed Research International,
Год журнала:
2017,
Номер
2017, С. 1 - 13
Опубликована: Янв. 1, 2017
Glioblastoma
(GBM)
is
a
primary
neuroepithelial
tumor
of
the
central
nervous
system,
characterized
by
an
extremely
aggressive
clinical
phenotype.
Patients
with
GBM
have
poor
prognosis
and
only
3–5%
them
survive
for
more
than
5
years.
The
current
treatment
standards
include
maximal
resection
followed
radiotherapy
concomitant
adjuvant
therapies.
Despite
these
therapeutic
regimens,
majority
patients
suffer
recurrence
due
to
molecular
heterogeneity
GBM.
Consequently,
number
potential
diagnostic,
prognostic,
predictive
biomarkers
been
investigated.
Some
them,
such
as
IDH
mutations,
1p19q
deletion,
MGMT
promoter
methylation,
EGFRvIII
amplification
are
frequently
tested
in
routine
practice.
With
development
sequencing
technology,
detailed
characterization
signatures
has
facilitated
personalized
approach
contributed
new
generation
anti-GBM
therapies
inhibitors
targeting
growth
factor
receptors,
vaccines,
antibody-based
drug
conjugates,
recently
blocking
immune
checkpoints.
In
this
article,
we
review
exciting
progress
towards
elucidating
novel
discuss
their
implications
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(19), С. 10373 - 10373
Опубликована: Сен. 26, 2021
Gliomas
are
the
most
common
central
nervous
system
tumors.
New
technologies,
including
genetic
research
and
advanced
statistical
methods,
revolutionize
therapeutic
approach
to
patient
reveal
new
points
of
treatment
options.
Moreover,
2021
World
Health
Organization
Classification
Tumors
Central
Nervous
System
has
fundamentally
changed
classification
gliomas
incorporated
many
molecular
biomarkers.
Given
rapid
progress
in
neuro-oncology,
here
we
compile
latest
on
prognostic
predictive
biomarkers
gliomas.
In
adult
patients,
IDH
mutations
positive
markers
have
greatest
significance.
However,
CDKN2A
deletion,
IDH-mutant
astrocytomas,
is
a
marker
highest
malignancy
grade.
presence
TERT
promoter
mutations,
EGFR
alterations,
or
combination
chromosome
7
gain
10
loss
upgrade
IDH-wildtype
astrocytoma
glioblastoma.
pediatric
H3F3A
alterations
important
which
predict
worse
outcome.
MGMT
methylation
clinical
significance
predicting
responses
temozolomide
(TMZ).
Conversely,
mismatch
repair
defects
cause
hypermutation
phenotype
poor
response
TMZ.
Finally,
discussed
liquid
biopsies,
promising
diagnostic,
prognostic,
techniques,
but
further
work
needed
implement
these
novel
technologies
practice.
Current Drug Targets,
Год журнала:
2019,
Номер
20(12), С. 1217 - 1226
Опубликована: Июнь 19, 2019
Phosphoinositide
3-kinase
(PI3Ks)
is
a
member
of
intracellular
lipid
kinases
and
involved
in
the
regulation
cellular
proliferation,
differentiation
survival.
Overexpression
PI3K/Akt/mTOR
signalling
has
been
reported
various
forms
cancers,
especially
colorectal
cancers
(CRC).
Due
to
their
significant
roles
initiation
progression
events
cancer,
they
are
recognized
as
striking
therapeutic
target.The
present
review
aimed
provide
detailed
outline
on
role
pathway
well
its
function
drug
resistance.
Further,
inhibitors
alone
combination
with
other
chemotherapeutic
drugs,
alleviating
cancer
also
discussed.
The
contains
preclinical
clinical
evidence
patent
literature
which
natural
synthetic
origin.The
data
were
obtained
from
PubMed/Medline
databases,
Scopus
Google
literature.PI3K/Akt/mTOR
an
important
event
carcinogenesis.
In
addition,
it
plays
acquiring
resistance
metastatic
CRCs.
Several
small
molecules
origin
have
found
be
potent
CRCs
by
effectively
downregulating
pathway.
Data
studies
support
these
several
among
them
patented.Inhibitors
PI3K/mTOR
successful
for
treatment
primary
rendering
promising
target.
Biomedicines,
Год журнала:
2019,
Номер
7(3), С. 69 - 69
Опубликована: Сен. 9, 2019
The
alkylating
agent
temozolomide
(TMZ)
together
with
maximal
safe
bulk
resection
and
focal
radiotherapy
comprises
the
standard
treatment
for
glioblastoma
(GB),
a
particularly
aggressive
lethal
primary
brain
tumor.
GB
affects
3.2
in
100,000
people
who
have
an
average
survival
time
of
around
14
months
after
presentation.
Several
key
aspects
make
difficult
to
treat
disease,
primarily
including
high
resistance
tumor
cells
cell
death-inducing
substances
or
radiation
combination
highly
invasive
nature
malignancy,
i.e.,
must
affect
whole
brain,
protection
from
drugs
bulk—or
at
least
invading
cells—by
blood
barrier
(BBB).
TMZ
crosses
BBB,
but—unlike
classic
chemotherapeutics—does
not
induce
DNA
damage
misalignment
segregating
chromosomes
directly.
It
has
been
described
as
agent,
which
leads
base
mismatches
that
initiate
futile
repair
cycles;
eventually,
strand
breaks,
turn
induces
death.
However,
while
much
is
assumed
about
function
its
mode
action,
data
are
actually
scarce
often
contradictory.
To
improve
further,
we
need
fully
understand
what
does
their
microenvironment.
This
particular
importance,
novel
therapeutic
approaches
almost
always
clinically
assessed
presence
treatment,
TMZ.
Therefore,
potential
pharmacological
interactions
between
might
occur
unforeseeable
consequences.
Cancer Discovery,
Год журнала:
2020,
Номер
10(3), С. 371 - 381
Опубликована: Янв. 9, 2020
Glioblastoma
(GBM)
is
a
lethal
brain
tumor
containing
subpopulation
of
glioma
stem
cells
(GSC).
Pan-cancer
analyses
have
revealed
that
stemness
cancer
correlates
positively
with
immunosuppressive
pathways
in
many
solid
tumors,
including
GBM,
prompting
us
to
conduct
gain-of-function
screen
epigenetic
regulators
may
influence
GSC
self-renewal
and
immunity.
The
circadian
regulator
CLOCK
emerged
as
top
hit
enhancing
stem-cell
self-renewal,
which
was
amplified
about
5%
human
GBM
cases.
its
heterodimeric
partner
BMAL1
enhanced
triggered
protumor
immunity
via
transcriptional
upregulation
OLFML3,
novel
chemokine
recruiting
immune-suppressive
microglia
into
the
microenvironment.
In
models,
or
OLFML3
depletion
reduced
intratumoral
density
extended
overall
survival.
We
conclude
CLOCK-BMAL1
complex
contributes
key
hallmarks
maintenance
immunosuppression
and,
together
downstream
target
represents
new
therapeutic
targets
for
this
disease.
SIGNIFICANCE:
Circadian
drives
metabolism
promotes
infiltration
through
direct
regulation
microglia-attracting
chemokine,
OLFML3.
and/or
represent
GBM.This
article
highlighted
This
Issue
feature,
p.
327.
Cellular Oncology,
Год журнала:
2019,
Номер
43(1), С. 123 - 136
Опубликована: Ноя. 12, 2019
Gemcitabine
(GEM)-based
chemotherapy
is
the
first-line
treatment
for
locally
advanced
pancreatic
cancer.
GEM
resistance,
however,
remains
a
significant
clinical
challenge.
Here,
we
investigated
whether
exosomes
derived
from
GEM-resistant
cancer
stem
cells
(CSCs)
mediate
cell-cell
communication
between
that
are
sensitive
or
resistant
to
and,
by
doing
so,
regulate
drug
resistance.GEM-sensitive
BxPC-3-derived
BxS
and
PANC-1
were
cultured
with
extracted
CSCs
isolated
BxR
(BxR-CSC).
The
effect
of
on
cell
cycle
progression,
apoptosis
miRNA
expression
was
evaluated
in
cells.
Relevant
miRNAs
associated
resistance
identified
role
miR-210
conferring
examined
vitro
vivo.BxR-CSC-derived
induced
inhibited
GEM-induced
arrest,
antagonized
apoptosis,
promoted
tube
formation
migration
Elevated
levels
detected
BxR-CSCs
BxR-CSC-derived
compared
those
BxS-CSCs
BxS-CSC-derived
exosomes.
In
addition,
increased
observed
upon
exposure
dose-dependent
manner.
Also,
series
biological
changes
after
transfection
mimics,
including
activation
mammalian
target
rapamycin
(mTOR)
signaling
pathway,
these
similar
triggered
exosomes.Our
findings
suggest
horizontal
transfer
drug-resistant
traits
GEM-sensitive
delivering
miR-210.
Stem Cell Research & Therapy,
Год журнала:
2021,
Номер
12(1)
Опубликована: Март 24, 2021
Abstract
Glioblastoma
(GBM)
is
the
highest-grade
form
of
glioma,
as
well
one
most
aggressive
types
cancer,
exhibiting
rapid
cellular
growth
and
highly
invasive
behavior.
Despite
significant
advances
in
diagnosis
therapy
recent
decades,
outcomes
for
high-grade
gliomas
(WHO
grades
III-IV)
remain
unfavorable,
with
a
median
overall
survival
time
15–18
months.
The
concept
cancer
stem
cells
(CSCs)
has
emerged
provided
new
insight
into
GBM
resistance
management.
CSCs
can
self-renew
initiate
tumor
are
also
responsible
cell
heterogeneity
induction
systemic
immunosuppression.
idea
that
could
be
dependent
on
innate
differences
sensitivity
clonogenic
glial
(GSCs)
to
chemotherapeutic
drugs/radiation
prompted
scientific
community
rethink
understanding
therapies
directed
at
eliminating
these
or
modulating
their
stemness.
This
review
aims
describe
major
intrinsic
extrinsic
mechanisms
mediate
chemoradioresistant
GSCs
based
antineoplastic
agents
from
natural
sources,
derivatives,
synthetics
used
alone
synergistic
combination
conventional
treatment.
We
will
address
ongoing
clinical
trials
focused
promising
targets.
Although
development
effective
remains
challenge
molecular
oncology,
GSC
knowledge
offer
directions
future.
Frontiers in Oncology,
Год журнала:
2022,
Номер
12
Опубликована: Июль 14, 2022
Sterol
regulatory
element
binding
protein-1
(SREBP-1),
a
transcription
factor
with
basic
helix–loop–helix
leucine
zipper,
has
two
isoforms,
SREBP-1a
and
SREBP-1c,
derived
from
the
same
gene
for
regulating
genes
of
lipogenesis,
including
acetyl-CoA
carboxylase,
fatty
acid
synthase,
stearoyl-CoA
desaturase.
Importantly,
SREBP-1
participates
in
metabolic
reprogramming
various
cancers
been
biomarker
prognosis
or
drug
efficacy
patients
cancer.
In
this
review,
we
first
introduced
structure,
activation,
key
upstream
signaling
pathway
SREBP-1.
Then,
potential
targets
molecular
mechanisms
SREBP-1-regulated
lipogenesis
types
cancer,
such
as
colorectal,
prostate,
breast,
hepatocellular
were
summarized.
We
also
discussed
therapies
targeting
by
small
molecules,
natural
products,
extracts
herbs
against
tumor
progression.
This
review
could
provide
new
insights
understanding
advanced
findings
about
SREBP-1-mediated
cancer
its
target
therapeutics.