Frontiers in Immunology,
Год журнала:
2018,
Номер
9
Опубликована: Май 8, 2018
Glioblastomas
(GBMs)
are
the
most
common
and
aggressive
primary
brain
tumors.
Due
to
their
malignant
growth
invasion
into
parenchyma
coupled
with
resistance
therapy,
GBMs
among
deadliest
of
all
cancers.
highly
heterogeneous
at
both
molecular
histological
levels.
Hallmark
structures
include
pseudopalisading
necrosis
microvascular
proliferation.
In
addition
high
levels
intratumoral
heterogeneity,
also
exhibit
inter-tumoral
heterogeneity.
The
major
non-neoplastic
cell
population
in
GBM
microenvironment
includes
cells
innate
immune
system
called
tumor-associated
macrophages
(TAMs).
Correlative
data
from
literature
suggest
that
molecularly
distinct
subtypes
differences
microenvironment.
Data
mouse
models
genetic
driver
mutations
can
create
unique
microenvironments.
Here,
we
review
origin,
features,
functions
TAMs
subtypes.
We
discuss
interactions
other
constituents
prospects
therapeutically
targeting
increase
efficacy
T-cell
functions.
Science,
Год журнала:
2018,
Номер
360(6389), С. 660 - 663
Опубликована: Май 10, 2018
Glioblastoma
is
an
aggressive
brain
tumor
that
carries
a
poor
prognosis.
The
tumor's
molecular
and
cellular
landscapes
are
complex,
their
relationships
to
histologic
features
routinely
used
for
diagnosis
unclear.
We
present
the
Ivy
Atlas,
anatomically
based
transcriptional
atlas
of
human
glioblastoma
aligns
individual
with
genomic
alterations
gene
expression
patterns,
thus
assigning
information
most
important
morphologic
hallmarks
tumor.
its
clinical
database
freely
accessible
online
data
resources
will
serve
as
valuable
platform
future
investigations
pathogenesis,
diagnosis,
treatment.
Cancer Cell,
Год журнала:
2021,
Номер
39(4), С. 509 - 528.e20
Опубликована: Фев. 11, 2021
Glioblastoma
(GBM)
is
the
most
aggressive
nervous
system
cancer.
Understanding
its
molecular
pathogenesis
crucial
to
improving
diagnosis
and
treatment.
Integrated
analysis
of
genomic,
proteomic,
post-translational
modification
metabolomic
data
on
99
treatment-naive
GBMs
provides
insights
GBM
biology.
We
identify
key
phosphorylation
events
(e.g.,
phosphorylated
PTPN11
PLCG1)
as
potential
switches
mediating
oncogenic
pathway
activation,
well
targets
for
EGFR-,
TP53-,
RB1-altered
tumors.
Immune
subtypes
with
distinct
immune
cell
types
are
discovered
using
bulk
omics
methodologies,
validated
by
snRNA-seq,
correlated
specific
expression
histone
acetylation
patterns.
Histone
H2B
in
classical-like
immune-low
driven
largely
BRDs,
CREBBP,
EP300.
proteomic
lipid
distributions
across
global
metabolic
changes
IDH-mutated
This
work
highlights
biological
relationships
that
could
contribute
stratification
patients
more
effective
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Апрель 16, 2019
Abstract
The
identity
and
unique
capacity
of
cancer
stem
cells
(CSC)
to
drive
tumor
growth
resistance
have
been
challenged
in
brain
tumors.
Here
we
report
that
expressing
CSC-associated
cell
membrane
markers
Glioblastoma
(GBM)
do
not
represent
a
clonal
entity
defined
by
distinct
functional
properties
transcriptomic
profiles,
but
rather
plastic
state
most
can
adopt.
We
show
phenotypic
heterogeneity
arises
from
non-hierarchical,
reversible
transitions,
instructed
the
microenvironment
is
predictable
mathematical
modeling.
Although
were
similar
vitro,
accelerated
reconstitution
provides
advantage
vivo,
suggesting
tumorigenic
potential
linked
intrinsic
plasticity
than
CSC
multipotency.
any
given
reconstitute
cautions
against
therapies
targeting
epitopes.
Instead
inherent
emerges
as
novel
relevant
target
for
treatment.
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Июль 8, 2020
Cancer
stem
cells
are
critical
for
cancer
initiation,
development,
and
treatment
resistance.
Our
understanding
of
these
processes,
how
they
relate
to
glioblastoma
heterogeneity,
is
limited.
To
overcome
limitations,
we
performed
single-cell
RNA
sequencing
on
53586
adult
22637
normal
human
fetal
brain
cells,
compared
the
lineage
hierarchy
developing
transcriptome
cells.
We
find
a
conserved
neural
tri-lineage
centered
around
glial
progenitor-like
also
that
this
progenitor
population
contains
majority
cancer's
cycling
and,
using
velocity,
often
originator
other
cell
types.
Finally,
show
hierarchal
map
can
be
used
identify
therapeutic
targets
specific
analyses
development
reconciles
suggests
possible
origin
hierarchy,
helps
cell-specific
targets.
