| Title |
PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform
|
|---|---|
| Published in |
PLOS ONE, August 2012
|
| DOI | 10.1371/journal.pone.0040452 |
| Pubmed ID | |
| Authors |
Shi-He Liu, Donald D. Rao, John Nemunaitis, Neil Senzer, Guisheng Zhou, David Dawson, Marie-Claude Gingras, Zhaohui Wang, Richard Gibbs, Michael Norman, Nancy S. Templeton, Francesco J. DeMayo, Bert O'Malley, Robbi Sanchez, William E. Fisher, F. Charles Brunicardi |
| Abstract |
Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a "drugable" target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNA(PDX-1), was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNA(humanPDX-1) lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNA(mousePDX-1) lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNA(mousePDX-1) lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 33% |
| Canada | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 28 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 36% |
| Researcher | 8 | 29% |
| Student > Master | 3 | 11% |
| Lecturer | 1 | 4% |
| Student > Bachelor | 1 | 4% |
| Other | 2 | 7% |
| Unknown | 3 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 29% |
| Medicine and Dentistry | 8 | 29% |
| Biochemistry, Genetics and Molecular Biology | 5 | 18% |
| Psychology | 1 | 4% |
| Social Sciences | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 4 | 14% |