| http://purl.uniprot.org/citations/23338611 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23338611 | http://www.w3.org/2000/01/rdf-schema#comment | "Deregulated TGF-β signaling in pancreatic cancer promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network. A strategy for disrupting this tumor-promoting pathway is silencing TGF-β by siRNA. By introducing a triphosphate group at the 5' end of siRNA (ppp-siRNA), gene silencing can be combined with immune activation via the cytosolic helicase retinoic acid-inducible gene I (RIG-I), a ubiquitously expressed receptor recognizing viral RNA. We validated RIG-I as a therapeutic target by showing that activation of RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production of type I IFN, the chemokine CXCL10, as well as caspase-9-mediated tumor cell apoptosis. Next, we generated a bifunctional ppp-siRNA that combines RIG-I activation with gene silencing of TGF-β1 (ppp-TGF-β) and studied its therapeutic efficacy in the orthotopic Panc02 mouse model of pancreatic cancer. Intravenous injection of ppp-TGF-β reduced systemic and tumor-associated TGF-β levels. In addition, it induced high levels of type I IFN and CXCL10 in serum and tumor tissue, systemic immune cell activation, and profound tumor cell apoptosis in vivo. Treatment of mice with established tumors with ppp-TGF-β significantly prolonged survival as compared with ppp-RNA or TGF-β siRNA alone. Furthermore, we observed the recruitment of activated CD8(+) T cells to the tumor and a reduced frequency of CD11b(+) Gr-1(+) myeloid cells. Therapeutic efficacy was dependent on CD8(+) T cells, whereas natural killer cells were dispensable. In conclusion, combing TGF-β gene silencing with RIG-I signaling confers potent antitumor efficacy against pancreatic cancer by breaking tumor-induced CD8(+) T cell suppression."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-11-3850"xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Wei J."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Endres S."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Hartmann G."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Poeck H."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Duewell P."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Anders H.J."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Schnurr M."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Mayr D."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Hoves S."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Adunka T."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Ellermeier J."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Noerenberg D."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/author | "Stieg M.R."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/pages | "1709-1720"xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/title | "Therapeutic efficacy of bifunctional siRNA combining TGF-beta1 silencing with RIG-I activation in pancreatic cancer."xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://purl.uniprot.org/core/volume | "73"xsd:string |
| http://purl.uniprot.org/citations/23338611 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23338611 |
| http://purl.uniprot.org/citations/23338611 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23338611 |
| http://purl.uniprot.org/uniprot/#_E9Q6I6-mappedCitation-23338611 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23338611 |
| http://purl.uniprot.org/uniprot/#_A1L0V6-mappedCitation-23338611 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23338611 |