Abstract
This
study
provides
an
analysis
of
37
ovarian
Sertoli–Leydig
cell
tumors
(SLCT),
focusing
on
their
morphological,
immunohistochemical,
and
molecular
features.
The
cohort
was
comprised
9
well-differentiated,
25
moderately
differentiated,
3
poorly
differentiated
tumors.
immunohistochemical
performed
with
28
markers,
including
diagnostic
markers
possible
predictive
significance.
results
showed
high
expression
sex
cord
(FOXL2,
SF1,
inhibin
A,
CD99,
calretinin,
ER,
PR,
AR),
variable
other
such
as
CKAE1/3
(83%),
CAIX
(14%),
MUC4
(1%).
Loss
PTEN
present
in
14%
cases,
CTLA4
seen
43%
cases.
All
were
MMR
proficient
HER2
PD-L1
negative.
DICER1
mutations
54.5%
a
FOXL2
mutation
6%
In
addition,
we
detected
2
cases
TERT
promoter
mutation.
RNA
NGS
sequencing
identified
significant
differences
mRNA
between
MUT
WT
increased
PRKCA
,
HNF1A
LDLR
MAP2K5
.
On
the
contrary,
CDK6
NOTCH2
FGFR2
our
show
that
SLCTs
exhibit
distinct
features
based
degree
differentiation.
We
have
confirmed
are
characteristic
SLCTs,
while
well-differentiated
may
represent
entity.
different
profiles.
is
less
common
these
mutually
exclusive
Abstract
Capivasertib
has
emerged
as
a
promising
treatment
for
advanced
breast
and
prostate
cancer.
Here,
we
report
two
cases
of
metastatic
cancer
patients
who
developed
splenic
hypermetabolism
on
[18
F]-FDG
PET/CT
following
with
capivasertib.
To
our
knowledge,
these
are
the
first
documented
instances
this
treatment-related
phenomenon.
Although
mechanism
behind
side
effect
remains
unclear,
highlight
an
important
imaging
phenomenon
that
radiologists
should
consider
when
interpreting
scans
in
treated
Critical Reviews in Oncology/Hematology,
Год журнала:
2024,
Номер
200, С. 104404 - 104404
Опубликована: Май 28, 2024
The
results
of
the
SOLAR-1
and
CAPItello-291,
highlight
benefit
ɑ-selective
phosphoinositide
3-Kinase
Pathway
inhibitor
(PI3Ki)
alpelisib
AKT
(AKTi)
capivasertib
in
patients
with
hormone
receptor-positive
(HR+)/Human
Epidermal
Growth
Factor
Receptor
2
(HER2)-
negative
metastatic
breast
cancer
(mBC)
that
have
PIK3CA/AKT1/PTEN
tumour
alterations.
Although
effective,
these
drugs
are
associated
significant
toxicities,
which
often
limit
their
use,
particularly
frail
patients.
Following
recent
incorporation
agents
into
clinical
practice,
many
others
currently
development,
challenges
emerged,
those
regarding
biomarkers
for
patient
selection.
This
review
will
discuss
response
resistance
to
PI3K/AKT
inhibitors
(PI3K/AKTis)
HR+/HER-
BC
early
advanced
settings
ascertain
populations
most
from
drugs.
Of
were
analysed,
such
as
PIK3CA,
AKT,
PTEN
mutations,
insulin
levels,
Virus Research,
Год журнала:
2024,
Номер
348, С. 199447 - 199447
Опубликована: Авг. 9, 2024
One
third
of
all
emerging
infectious
diseases
are
vector-borne,
with
no
licensed
antiviral
therapies
available
against
any
vector-borne
viruses.
Zika
virus
and
Usutu
two
flaviviruses
transmitted
primarily
by
mosquitoes.
These
viruses
modulate
different
host
pathways,
including
the
PI3K/AKT/mTOR
pathway.
Here,
we
report
effect
on
ZIKV
USUV
replication
AKT
inhibitors,
Miransertib
(ARQ-092,
allosteric
inhibitor)
Capivasertib
(AZD5363,
competitive
in
mammalian
mosquito
cell
lines.
showed
a
stronger
inhibitory
than
cells,
while
cells.
findings
indicate
that
plays
conserved
role
flavivirus
infection,
both
vertebrate
invertebrate
vector.
Nevertheless,
specific
function
may
vary
depending
species.
be
playing
infection
both,
However,
A
better
understanding
virus-host
interactions
is
therefore
required
to
develop
new
treatments
prevent
human
disease
approaches
control
transmission
insect
vectors.
Molecules,
Год журнала:
2024,
Номер
29(17), С. 4203 - 4203
Опубликована: Сен. 4, 2024
This
study
evaluates
radio-iodinated
anastrozole
([125I]anastrozole)
and
epirubicin
([125I]epirubicin)
for
AKT1-targeted
breast
cancer
therapy,
utilizing
radiopharmaceutical
therapy
(RPT)
personalized
treatment.
Through
molecular
docking
dynamics
simulations
(200
ns),
it
investigates
these
compounds’
binding
affinities
mechanisms
to
the
AKT1
enzyme,
compared
co-crystallized
ligand,
a
known
inhibitor.
Molecular
results
show
that
[125I]epirubicin
has
highest
ΔGbind
(−11.84
kcal/mol),
indicating
superior
affinity
[125I]
(−10.68
kcal/mol)
ligand
(−9.53
kcal/mol).
(MD)
confirmed
stable
interaction
with
[125I]anastrozole
reaching
stability
after
approximately
68
ns
an
average
RMSD
of
around
2.2
Å,
while
stabilized
at
2.69
Å
87
ns.
RMSF
analysis
showed
no
significant
shifts
in
residues
or
segments,
consistent
patterns
differences
less
than
2
maintaining
enzyme
stability.
The
complex
maintained
four
H-bonds,
strong
interactions,
consistently
formed
three
H-bonds.
Rg
values
both
complexes
were
~16.8
±
0.1
changes
enzyme’s
compactness,
thus
preserving
structural
integrity.
These
analyses
reveal
minimal
perturbations,
suggesting
high
potential
inhibition.
MM-PBSA
calculations
confirm
compounds
as
inhibitors,
exhibiting
most
favorable
energy
(−23.57
0.14
(−20.03
0.15
(−16.38
highlighting
role
electrostatic
interactions
stabilizing
complex.
computational
shows
may
play
promising
roles
especially
its
dynamic
receptor
interactions.
findings,
supported
by
scores
energies,
advocate
their
inhibitory
capability
against
enzyme.
Nevertheless,
is
crucial
validate
predictions
through
vitro
vivo
studies
thoroughly
evaluate
therapeutic
viability
Kinases and Phosphatases,
Год журнала:
2024,
Номер
2(4), С. 346 - 378
Опубликована: Дек. 12, 2024
Protein
kinases
(PKs)
are
an
important
and
very
popular
family
of
enzymes
that
play
a
vital
role
in
regulating
cellular
processes
via
the
phosphorylation
targets.
Nevertheless,
modifications
expression
due
to
mutations
or
their
dysregulation
can
lead
diseases,
including
autoimmune
disorders,
cardiovascular
problems,
diabetes,
neurological
cancers.
Cyclic
ultra-short
peptides
amazing
structures
with
unique
properties.
The
cyclicity
cyclic
(CPs)
mimic
interactions
between
PKs
natural
substrates,
influencing
enzyme
activity
essential
health
disease
physiology.
Our
review
summarized
interference
signal
transduction
mechanism
by
CPs
implies
inhibition
substrate
at
level
active
site,
similar
anti-neoplastic
drugs.
remarkable
capacity
interact
targets
positions
them
as
promising
candidates
for
developing
protein
kinase
inhibitors
treating
diseases.
This
offers
new
insights
molecular
mechanisms,
cytotoxicity,
target
selectivity,
possibility
designing
more
effective
safe
therapeutic
agents.
