Abstract |
The stubborn chemoresistance of pancreatic ductal adenocarcinoma (PDA) is simultaneously influenced by tumor parenchymal and stromal factors, and the ctritical role of Notch ligand Delta-like 4 (DLL4) in the regulation of tumor malignancies has been observed. DLL4 positive expression ratio between duct cells from clinical tumor and adjacent tissues was statistically significant, and the overactivation of DLL4/Notch pathway enhanced the phenotype of EMT and cancer stem cell, even can induce multi-chemoresistance in vitro. Notably, the accompanied defective angiogenesis directly induced inefficient chemo-drug delivery in vivo. Collectively, overexpressed DLL4 on neoplastic cells can enhance chemoresistance through angiogenesis-dependent/independent mechanisms in PDA.
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Authors | Muxing Kang, Biao Jiang, Bin Xu, Wenjie Lu, Qingqu Guo, Qiuping Xie, Bo Zhang, Xin Dong, Daniel Chen, Yulian Wu |
Journal | Cancer letters
(Cancer Lett)
Vol. 330
Issue 1
Pg. 11-21
(Mar 01 2013)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 23200678
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Adaptor Proteins, Signal Transducing
- Antibiotics, Antineoplastic
- Calcium-Binding Proteins
- DLL4 protein, human
- Intercellular Signaling Peptides and Proteins
- NOTCH1 protein, human
- NOTCH2 protein, human
- Receptor, Notch1
- Receptor, Notch2
- Doxorubicin
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Topics |
- Adaptor Proteins, Signal Transducing
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Calcium-Binding Proteins
- Carcinoma, Pancreatic Ductal
(drug therapy, metabolism, pathology)
- Cell Line, Tumor
- Doxorubicin
(pharmacology)
- Drug Delivery Systems
- Drug Resistance, Neoplasm
- Female
- Humans
- Immunohistochemistry
- Intercellular Signaling Peptides and Proteins
(biosynthesis, genetics, metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, SCID
- Pancreatic Neoplasms
(drug therapy, metabolism, pathology)
- Receptor, Notch1
(biosynthesis)
- Receptor, Notch2
(biosynthesis)
- Xenograft Model Antitumor Assays
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