| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T14143 | ||||
| Target Name | Transforming growth factor beta 2 | ||||
| Target Type | Clinical Trial |
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| Action against Disease Model | AP12009 | Trabedersen (AP 12009) is a phosphorothioate antisense oligodeoxynucleotide specific for h uMan TGF-|?? mRNA. Trabedersen reduced TGF-|?? secretion in h uMan pancreatic cell lines with an IC(50) in the low |?M range without transfection reagent, clearly inhibited cell proliferation, and completely blocked migration of pancreatic cancer cells. Additionally, trabedersen reversed TGF-|??-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 t uMor growth, lymph node metastasis and angiogenesis. | [553093] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Targeted disruption of the TGFbeta2 gene was undertaken to determine its essential role in vivo. TGFbeta2-null mice exhibit perinatal mortality and a wide range of developmentaldefects for a single gene disruption. These include cardiac, lung, craniofacial, limb, spinal col uMn, eye, inner ear and urogenital defects. The developmental processes most commonly involved in theaffected tissues include epithelial-mesenchymal interactions, cell growth, extracellular matrix production and tissue remodeling. In addition, many affected tissues have neural crest-derived components and simulate neural crest deficiencies. There is no phenotypic overlap with TGFbeta1- and TGFbeta3-null mice indicating n uMerous non-compensated functions between the TGFbeta isoforms | [553093] | |||
| References | |||||
| Ref 553093 | Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci. 2011 Jun;102(6):1193-200. doi: 10.1111/j.1349-7006.2011.01917.x. Epub 2011 Mar 30. | ||||
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