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Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma.
[esophageal adenocarcinoma]
Esophageal
adenocarcinoma
ranks
sixth
in
cancer
mortality
in
the
world
and
its
incidence
has
risen
dramatically
in
the
Western
population
over
the
last
decades
.
Data
presented
herein
strongly
suggest
that
Notch
signaling
is
critical
for
esophageal
adenocarcinoma
and
underlies
resistance
to
chemotherapy
.
We
present
evidence
that
Notch
signaling
drives
a
cancer
stem
cell
phenotype
by
regulating
genes
that
establish
stemness
.
Using
patient-derived
xenograft
models
,
we
demonstrate
that
inhibition
of
Notch
by
gamma-secretase
inhibitors
(
GSI
)
is
efficacious
in
downsizing
tumor
growth
.
Moreover
,
we
demonstrate
that
Notch
activity
in
a
patient
's
ultrasound-assisted
endoscopic-derived
biopsy
might
predict
outcome
to
chemotherapy
.
Therefore
,
this
study
provides
a
proof
of
concept
that
inhibition
of
Notch
activity
will
have
efficacy
in
treating
esophageal
adenocarcinoma
,
offering
a
rationale
to
lay
the
foundation
for
a
clinical
trial
to
evaluate
the
efficacy
of
GSI
in
esophageal
adenocarcinoma
treatment
.
Cancer
Res
;
74
(
21
)
;
6364
-
74
.
©
2014
AACR
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated