Clinical and Translational Medicine,
Год журнала:
2018,
Номер
7(1)
Опубликована: Окт. 10, 2018
Combination
therapy
is
increasingly
becoming
the
cornerstone
of
current
day
antitumor
therapy.
Glioblastoma
multiforme
an
aggressive
brain
tumor
with
a
dismal
median
survival
post
diagnosis
and
high
rate
disease
recurrence.
The
poor
prognosis
can
be
attributed
to
unique
treatment
limitations,
which
include
infiltrative
nature
cells,
failure
anti-glioma
drugs
cross
blood-brain
barrier,
heterogeneity
highly
metastatic
angiogenic
making
cells
resistant
chemotherapy.
approach
being
developed
against
glioblastoma
new
innovative
combination
drug
regimens
tested
in
preclinical
clinical
trials.
In
this
review,
we
discuss
pathophysiology
glioblastoma,
diagnostic
markers,
therapeutic
targeting
strategies,
novel
therapies
context
options
ongoing
trials
for
Complex
rearrangement
patterns
and
mitotic
errors
are
hallmarks
of
most
pancreatic
ductal
adenocarcinomas
(PDAC),
a
disease
with
dismal
prognosis
despite
some
therapeutic
advances
in
recent
years.
DNA
double-strand
breaks
(DSB)
bear
the
greatest
risk
provoking
genomic
instability,
damage
repair
(DDR)
pathways
crucial
preserving
integrity
following
plethora
types.
Two
major
dominate
DSB
for
safeguarding
genome
integrity:
non-homologous
end
joining
homologous
recombination
(HR).
Defective
HR,
but
also
alterations
other
DDR
pathways,
such
as
BRCA1
,
BRCA2
ATM
PALB2,
occur
frequently
both
inherited
sporadic
PDAC.
Personalised
treatment
cancer
is
still
its
infancy
predictive
biomarkers
lacking.
deficiency
might
render
PDAC
vulnerable
to
potential
new
intervention
that
increases
load
beyond
tolerable
threshold,
example,
induced
by
poly
(ADP-ribose)
polymerase
inhibitors.
The
Pancreas
Cancer
Olaparib
Ongoing
(POLO)
trial,
which
olaparib
maintenance
improved
progression-free
survival
compared
placebo
after
platinum-based
induction
chemotherapy
patients
germline
BRCA1/2
mutations,
raised
great
hopes
substantially
outcome
this
patient
subgroup.
This
review
summarises
relationship
between
PDAC,
prevalence
characteristics
mutations
options
clinical
management
deficiency.
Journal of Cellular and Molecular Medicine,
Год журнала:
2019,
Номер
23(5), С. 3451 - 3463
Опубликована: Фев. 26, 2019
Abstract
Abnormal
metabolism
of
tumour
cells
is
closely
related
to
the
occurrence
and
development
breast
cancer,
during
which
expression
NF‐E2‐related
factor
2
(Nrf2)
great
significance.
Metastatic
cancer
one
most
common
causes
death
worldwide;
however,
molecular
mechanism
underlying
metastasis
remains
unknown.
In
this
study,
we
found
that
overexpression
Nrf2
promoted
proliferation
migration
cancers
cells.
Inhibition
Kelch‐like
ECH‐associated
protein
1
(Keap1)
reduced
glucose‐6‐phosphate
dehydrogenase
(G6PD)
transketolase
pentose
phosphate
pathway,
knockdown
Keap1
had
opposite
effects.
Our
results
further
showed
G6PD
Hypoxia‐inducing
1α
(HIF‐1α)
in
MCF‐7
MDA‐MB‐231
Overexpression
up‐regulated
Notch1
via
G6PD/HIF‐1α
pathway.
Notch
signalling
pathway
affected
by
affecting
its
downstream
gene
HES‐1,
regulated
EMT
The
suggest
a
potential
target
for
treatment
targeting
may
provide
promising
strategy
Nrf2‐driven
metastasis.
Genes,
Год журнала:
2018,
Номер
9(12), С. 629 - 629
Опубликована: Дек. 13, 2018
The
accurate
repair
of
DNA
is
critical
for
genome
stability
and
cancer
prevention.
double-strand
breaks
are
one
the
most
toxic
lesions;
however,
they
can
be
repaired
using
homologous
recombination.
Homologous
recombination
a
high-fidelity
pathway
that
uses
template
repair.
One
central
HR
step
RAD51
nucleoprotein
filament
formation
on
single-stranded
ends,
which
required
homology
search
strand
invasion
steps
HR.
tightly
controlled
by
many
positive
negative
regulators,
collectively
termed
mediators.
mediators
function
to
nucleate,
elongate,
stabilize,
disassemble
during
In
model
organisms,
paralogs
mediator
proteins
structurally
resemble
promote
its
activity.
New
functions
replication
in
flexibility
have
recently
been
uncovered.
Mutations
human
(RAD51B,
RAD51C,
RAD51D,
XRCC2,
XRCC3,
SWSAP1)
found
subset
breast
ovarian
cancers.
Despite
their
discovery
three
decades
ago,
few
advances
made
understanding
paralogs.
Here,
we
discuss
current
perspective
vivo
vitro
paralogs,
relationship
with
vertebrate
models.
Journal of Clinical Medicine,
Год журнала:
2018,
Номер
7(12), С. 542 - 542
Опубликована: Дек. 12, 2018
Evidence
has
recently
emerged
on
the
influence
of
gender
immune
system.
In
this
systematic
review
and
meta-analysis
phase
III
randomized
clinical
trials
(RCTs),
we
explored
impact
survival
in
patients
with
advanced
cancer
treated
checkpoint
inhibitors
(ICIs).
We
performed
a
comprehensive
search
literature
updated
to
April
2018,
including
Cochrane
Central
Register
Controlled
Trials,
PubMed,
EMBASE.
extracted
data
study
characteristics
risk
bias
duplicate.
Of
423
unique
citations,
21
RCTs
were
included,
inherently
12,635
patients.
Both
males
females
showed
reduced
death
associated
ICIs
use
(HR
0.73,
p
<
0.001
HR
0.77,
0.001,
respectively).
Subgroup
analyses
by
specific
ICI
similar
OS
both
genders
for
anti-PD-1/PDL-1.
Anti-CTLA-4
was
longer
men
only
0.012),
exception
melanoma
(in
women,
0.80,
=
0.006).
PFS
than
women
0.67,
0.100,
Conclusively,
more
favorable
outcomes
men,
particularly
anti-CTLA-4
agents.
melanoma,
not
gender-related
factors
may
anti-tumor
response
evoked
ICIs.
Cell Reports Medicine,
Год журнала:
2020,
Номер
1(1), С. 100004 - 100004
Опубликована: Апрель 1, 2020
In
the
absence
of
a
dominant
driving
mutation
other
than
uniformly
present
TP53
mutations,
deeper
understanding
biology
ovarian
high-grade
serous
cancer
(HGSC)
requires
analysis
at
functional
level,
including
post-translational
modifications.
Comprehensive
proteogenomic
and
phosphoproteomic
characterization
83
prospectively
collected
HGSC
appropriate
normal
precursor
tissue
samples
(fallopian
tube)
under
strict
control
ischemia
time
reveals
pathways
that
significantly
differentiate
between
relevant
tissues
in
context
homologous
repair
deficiency
(HRD)
status.
addition
to
confirming
key
features
from
previous
studies,
potential
survival-associated
signature
histone
acetylation
as
marker
HRD,
deep
phosphoproteomics
provides
insights
regarding
role
proliferation-induced
replication
stress
promoting
characteristic
chromosomal
instability
suggests
therapeutic
targets
for
use
precision
medicine
trials.
Ubiquitination
is
a
reversible
post-translational
modification
based
on
the
chemical
addition
of
ubiquitin
to
proteins
with
regulatory
effects
various
signaling
pathways.
can
alter
molecular
functions
tagged
substrates
respect
protein
turnover,
biological
activity,
subcellular
localization
or
protein–protein
interaction.
As
result,
wide
variety
cellular
processes
are
under
ubiquitination-mediated
control,
contributing
maintenance
homeostasis.
It
follows
that
dysregulation
ubiquitination
reactions
plays
relevant
role
in
pathogenic
states
human
diseases
such
as
neurodegenerative
diseases,
immune-related
pathologies
and
cancer.
In
recent
decades,
enzymes
ubiquitin–proteasome
system
(UPS),
including
E3
ligases
deubiquitinases
(DUBs),
have
attracted
attention
novel
druggable
targets
for
development
new
anticancer
therapeutic
approaches.
This
perspective
article
summarizes
peculiarities
shared
by
involved
reaction
which,
when
deregulated,
lead
tumorigenesis.
Accordingly,
an
overview
main
pharmacological
interventions
targeting
UPS
clinical
use
still
trials
provided,
also
highlighting
limitations
efficacy
these
Therefore,
attempts
circumvent
drug
resistance
side
well
UPS-related
emerging
technologies
therapeutics
discussed.
Molecules,
Год журнала:
2018,
Номер
23(12), С. 3309 - 3309
Опубликована: Дек. 13, 2018
Coffee
is
one
of
the
most
popular
beverages
worldwide.
contains
bioactive
compounds
that
affect
human
body
such
as
caffeine,
caffeic
acid,
chlorogenic
acids,
trigonelline,
diterpenes,
and
melanoidins.
Some
them
have
demonstrated
potential
anticarcinogenic
effects
in
animal
models
cell
cultures,
may
play
a
protective
role
against
colorectal
cancer.
Colorectal
cancer
(CRC)
third
leading
cause
cancer-related
mortality
USA
other
countries.
Dietary
patterns,
well
consumption
beverages,
reduce
risk
CRC
incidence.
In
this
review,
we
focus
on
published
epidemiological
studies
concerning
association
coffee
development
cancer,
provide
description
selected
biologically
active
been
investigated
cancer-combating
compounds:
Caffeine,
acid
(CA),
acids
(CGAs),
kahweol
relation
to
progression
vitro
settings.
We
review
impact
these
substances
proliferation,
viability,
invasiveness,
metastasis,
susceptibility
chemo-
radiotherapy
lines
cultured
vitro.
