% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Zhang:127854,
author = {Y. Zhang$^*$ and L. Liu$^*$ and P. Fan$^*$ and N. Bauer$^*$
and J. Gladkich$^*$ and E. Ryschich and A. V. Bazhin and N.
A. Giese and O. Strobel and T. Hackert and U. Hinz and W.
Gross$^*$ and F. Fortunato and I. Herr$^*$},
title = {{A}spirin counteracts cancer stem cell features,
desmoplasia and gemcitabine resistance in pancreatic
cancer.},
journal = {OncoTarget},
volume = {6},
number = {12},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-03876},
pages = {9999 - 10015},
year = {2015},
abstract = {Pancreatic ductal adenocarcinoma (PDA) is characterized by
an extremely poor prognosis. An inflammatory
microenvironment triggers the pronounced desmoplasia, the
selection of cancer stem-like cells (CSCs) and therapy
resistance. The anti-inflammatory drug aspirin is suggested
to lower the risk for PDA and to improve the treatment,
although available results are conflicting and the effect of
aspirin to CSC characteristics and desmoplasia in PDA has
not yet been investigated. We characterized the influence of
aspirin on CSC features, stromal reactions and gemcitabine
resistance. Four established and 3 primary PDA cell lines,
non-malignant cells, 3 patient tumor-derived CSC-enriched
spheroidal cultures and tissues from patients who did or did
not receive aspirin before surgery were analyzed using MTT
assays, flow cytometry, colony and spheroid formation
assays, Western blot analysis, antibody protein arrays,
electrophoretic mobility shift assays (EMSAs),
immunohistochemistry and in vivo xenotransplantation.
Aspirin significantly induced apoptosis and reduced the
viability, self-renewal potential, and expression of
proteins involved in inflammation and stem cell signaling.
Aspirin also reduced the growth and invasion of tumors in
vivo, and it significantly prolonged the survival of mice
with orthotopic pancreatic xenografts in combination with
gemcitabine. This was associated with a decreased expression
of markers for progression, inflammation and desmoplasia.
These findings were confirmed in tissue samples obtained
from patients who had or had not taken aspirin before
surgery. Importantly, aspirin sensitized cells that were
resistant to gemcitabine and thereby enhanced the
therapeutic efficacy. Aspirin showed no obvious toxic
effects on normal cells, chick embryos or mice. These
results highlight aspirin as an effective, inexpensive and
well-tolerated co-treatment to target inflammation,
desmoplasia and CSC features PDA.},
keywords = {Biomarkers, Tumor (NLM Chemicals) / Deoxycytidine (NLM
Chemicals) / gemcitabine (NLM Chemicals) / Aspirin (NLM
Chemicals)},
cin = {G403},
ddc = {610},
cid = {I:(DE-He78)G403-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25846752},
pmc = {pmc:PMC4496413},
doi = {10.18632/oncotarget.3171},
url = {https://inrepo02.dkfz.de/record/127854},
}