PLoS Biology,
Год журнала:
2016,
Номер
14(8), С. e1002533 - e1002533
Опубликована: Авг. 19, 2016
Reported
values
in
the
literature
on
number
of
cells
body
differ
by
orders
magnitude
and
are
very
seldom
supported
any
measurements
or
calculations.
Here,
we
integrate
most
up-to-date
information
human
bacterial
body.
We
estimate
total
bacteria
70
kg
"reference
man"
to
be
3.8·1013.
For
cells,
identify
dominant
role
hematopoietic
lineage
count
(≈90%)
revise
past
estimates
3.0·1013
cells.
Our
analysis
also
updates
widely-cited
10:1
ratio,
showing
that
is
actually
same
order
as
their
mass
about
0.2
kg.
Nature,
Год журнала:
2020,
Номер
578(7793), С. 82 - 93
Опубликована: Фев. 5, 2020
Abstract
Cancer
is
driven
by
genetic
change,
and
the
advent
of
massively
parallel
sequencing
has
enabled
systematic
documentation
this
variation
at
whole-genome
scale
1–3
.
Here
we
report
integrative
analysis
2,658
whole-cancer
genomes
their
matching
normal
tissues
across
38
tumour
types
from
Pan-Cancer
Analysis
Whole
Genomes
(PCAWG)
Consortium
International
Genome
(ICGC)
The
Atlas
(TCGA).
We
describe
generation
PCAWG
resource,
facilitated
international
data
sharing
using
compute
clouds.
On
average,
cancer
contained
4–5
driver
mutations
when
combining
coding
non-coding
genomic
elements;
however,
in
around
5%
cases
no
drivers
were
identified,
suggesting
that
discovery
not
yet
complete.
Chromothripsis,
which
many
clustered
structural
variants
arise
a
single
catastrophic
event,
frequently
an
early
event
evolution;
acral
melanoma,
for
example,
these
events
precede
most
somatic
point
affect
several
cancer-associated
genes
simultaneously.
Cancers
with
abnormal
telomere
maintenance
often
originate
low
replicative
activity
show
mechanisms
preventing
attrition
to
critical
levels.
Common
rare
germline
patterns
mutation,
including
mutations,
retrotransposition.
A
collection
papers
describes
drive
beyond
those
TERT
promoter
4
;
identifies
new
signatures
mutational
processes
cause
base
substitutions,
small
insertions
deletions
5,6
analyses
timings
evolution
7
diverse
transcriptional
consequences
mutation
on
splicing,
expression
levels,
fusion
8,9
evaluates
range
more-specialized
features
8,10–18
Endocrine Reviews,
Год журнала:
2015,
Номер
36(6), С. E1 - E150
Опубликована: Ноя. 6, 2015
The
Endocrine
Society's
first
Scientific
Statement
in
2009
provided
a
wake-up
call
to
the
scientific
community
about
how
environmental
endocrine-disrupting
chemicals
(EDCs)
affect
health
and
disease.
Five
years
later,
substantially
larger
body
of
literature
has
solidified
our
understanding
plausible
mechanisms
underlying
EDC
actions
exposures
animals
humans—especially
during
development—may
lay
foundations
for
disease
later
life.
At
this
point
history,
we
have
much
stronger
knowledge
EDCs
alter
gene-environment
interactions
via
physiological,
cellular,
molecular,
epigenetic
changes,
thereby
producing
effects
exposed
individuals
as
well
their
descendants.
Causal
links
between
exposure
manifestation
are
substantiated
by
experimental
animal
models
consistent
with
correlative
epidemiological
data
humans.
There
several
caveats
because
differences
work
is
conducted
can
lead
difficulties
drawing
broad
conclusions,
must
continue
be
cautious
inferring
causality
In
second
Statement,
reviewed
on
subset
topics
which
translational
evidence
strongest:
1)
obesity
diabetes;
2)
female
reproduction;
3)
male
4)
hormone-sensitive
cancers
females;
5)
prostate;
6)
thyroid;
7)
neurodevelopment
neuroendocrine
systems.
Our
inclusion
criteria
studies
were
those
predominantly
past
5
deemed
high
quality
based
appropriate
negative
positive
control
groups
or
populations,
adequate
sample
size
design,
mammalian
levels
range
that
was
relevant
We
also
focused
using
developmental
origins
model.
No
report
excluded
effect
exposure.
bulk
results
across
board
strengthen
endocrine
health-related
EDCs.
Based
more
complete
principles
act,
including
nonmonotonic
dose-responses,
low-dose
effects,
vulnerability,
these
findings
better
translated
human
health.
Armed
information,
researchers,
physicians,
other
healthcare
providers
guide
regulators
policymakers
they
make
responsible
decisions.
Nature Reviews Gastroenterology & Hepatology,
Год журнала:
2020,
Номер
17(9), С. 557 - 588
Опубликована: Июнь 30, 2020
Abstract
Cholangiocarcinoma
(CCA)
includes
a
cluster
of
highly
heterogeneous
biliary
malignant
tumours
that
can
arise
at
any
point
the
tree.
Their
incidence
is
increasing
globally,
currently
accounting
for
~15%
all
primary
liver
cancers
and
~3%
gastrointestinal
malignancies.
The
silent
presentation
these
combined
with
their
aggressive
nature
refractoriness
to
chemotherapy
contribute
alarming
mortality,
representing
~2%
cancer-related
deaths
worldwide
yearly.
current
diagnosis
CCA
by
non-invasive
approaches
not
accurate
enough,
histological
confirmation
necessary.
Furthermore,
high
heterogeneity
CCAs
genomic,
epigenetic
molecular
levels
severely
compromises
efficacy
available
therapies.
In
past
decade,
efforts
have
been
made
understand
complexity
develop
new
diagnostic
tools
therapies
might
help
improve
patient
outcomes.
this
expert
Consensus
Statement,
which
endorsed
European
Network
Study
Cholangiocarcinoma,
we
aim
summarize
critically
discuss
latest
advances
in
CCA,
mostly
focusing
on
classification,
cells
origin,
genetic
abnormalities,
alterations,
biomarker
discovery
treatments.
horizon
next
decade
from
2020
onwards
highlighted.
Science,
Год журнала:
2015,
Номер
349(6255), С. 1483 - 1489
Опубликована: Сен. 24, 2015
Spontaneously
occurring
mutations
accumulate
in
somatic
cells
throughout
a
person’s
lifetime.
The
majority
of
these
do
not
have
noticeable
effect,
but
some
can
alter
key
cellular
functions.
Early
cause
developmental
disorders,
whereas
the
progressive
accumulation
life
lead
to
cancer
and
contribute
aging.
Genome
sequencing
has
revolutionized
our
understanding
mutation
cancer,
providing
detailed
view
mutational
processes
genes
that
drive
cancer.
Yet,
fundamental
gaps
remain
knowledge
how
normal
evolve
into
cells.
We
briefly
summarize
number
lessons
learned
over
5
years
genome
discuss
their
implications
for
progression
