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Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.
[primary effusion lymphoma]
Growing
evidence
supports
the
involvement
of
human
herpervirus
8
,
Kaposi
's
sarcoma
associated
herpesvirus
(
KSHV
)
,
in
the
pathology
of
primary
effusion
lymphoma
,
multicentric
Castleman
's
disease
,
and
Kaposi
's
sarcoma
,
but
the
exact
mechanism
of
KSHV
contribution
to
the
oncogenic
process
remains
elusive
.
We
studied
transgenic
mice
expressing
the
ORF
K
1
of
KSHV
,
whose
position
in
the
KSHV
genome
corresponds
to
known
lymphoproliferative
genes
of
other
herpesviruses
.
K
1
protein
was
previously
shown
to
contain
a
constitutively
active
ITAM
domain
,
involved
in
activation
of
Akt
and
pro-survival
signaling
,
and
to
inhibit
Fas-mediated
apoptosis
by
interfering
with
binding
of
FasL
.
All
this
pointed
to
a
possible
role
of
K
1
in
the
pathogenesis
of
KSHV-associated
cancers
.
K
1
transgenic
mice
(
80
-
90
%
)
developed
lymphoid
hyperplasia
and
splenomegaly
at
8
and
10
months
of
age
,
25
%
had
confirmed
diagnosis
of
lymphoma
,
and
50
%
developed
abdominal
and
/
or
hepatic
tumors
by
18
months
of
age
.
Histological
examination
showed
loss
of
splenic
architecture
and
increased
cellularity
.
Lymph
nodes
showed
disrupted
architecture
with
effaced
follicles
and
other
pathological
changes
,
including
signs
of
angiofollicular
lymphoid
hyperplasia
.
One
of
the
livers
showed
signs
of
angiosarcoma
.
In
summary
,
our
histology
results
revealed
pathological
changes
in
K
1
transgenic
mice
similar
to
lymphoma
,
Castleman
's
disease
,
and
angiosarcoma
,
suggesting
that
K
1
may
contribute
to
the
development
of
KSHV-associated
cancers
.
Diseases
Validation
Diseases presenting
"suggesting that k1 may contribute to the development of kshv-associated cancers"
symptom
primary effusion lymphoma
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