Schlingensiepen, Karl-Hermann and Jaschinski, Frank and Lang, Sven Arke and Moser, Christian and Geissler, Edward Kenneth and Schlitt, Hans Juergen and Kielmanowicz, Marcus and Schneider, Anneliese (2011) Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. CANCER SCIENCE, 102 (6). pp. 1193-1200. ISSN 1347-9032,
Full text not available from this repository. (Request a copy)Abstract
Pancreatic cancer is one of the most aggressive human cancers with a 5-year survival rate of < 5%. Overexpression of transforming growth factor-beta 2 (TGF-beta 2) in pancreatic malignancies is suggested to be a pivotal factor for malignant progression by inducing immunosuppression, metastasis, angiogenesis and proliferation. Trabedersen (AP 12009) is a phosphorothioate antisense oligodeoxynucleotide specific for human TGF-beta 2 mRNA and was successfully tested in a randomized, active-controlled phase IIb clinical study in patients with high-grade glioma. Here, we report on the antitumor activity of trabedersen in human pancreatic cancer cells and in an orthotopic xenograft mouse model of human metastatic pancreatic cancer. Trabedersen reduced TGF-beta 2 secretion in human pancreatic cell lines with an IC(50) in the low mu M range without transfection reagent, clearly inhibited cell proliferation, and completely blocked migration of pancreatic cancer cells. Additionally, trabedersen reversed TGF-beta 2-mediated immunosuppression of pancreatic cancer cells targeted by lymphokine activated killer (LAK) cells, resulting in considerably increased LAK cell-mediated cytotoxicity. Moreover, in an orthotopic mouse model of metastatic pancreatic cancer, intraperitoneal (i.p.) treatment with trabedersen significantly reduced tumor growth, lymph node metastasis and angiogenesis. These promising results warrant further clinical development of trabedersen. Cancer Sci 2011; 102: 1193-1200).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NUCLEIC-ACID CHANNEL; TGF-BETA; IN-VIVO; THERAPEUTIC APPROACH; MALIGNANT GLIOMAS; CARCINOMA CELLS; SIRNA DELIVERY; EXPRESSION; METASTASIS; TGF-BETA-2; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jun 2020 09:38 |
| Last Modified: | 15 Jun 2020 09:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20740 |
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