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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tammela, Tuomas Sahay, Gaurav Schroeder, Avi Jacks, Tyler Dave, Apeksha Dahlman, James E. Anderson, Daniel G. Langer, Robert Cai, Wenxin Xue, Wen Crowley, Denise G. Chirino, Leilani M. Bronson, Roderick Sood, Sabina Khan, Omar F. Yang, Gillian R. |
| Description | Author Affiliation: Xue W ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Dahlman JE ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Tammela T ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Khan OF ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Sood S ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Dave A ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Cai W ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Chirino LM ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Yang GR ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Bronson R ( Tufts University and Harvard Medical School, Boston, MA 02115); Crowley DG ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Sahay G ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Schroeder A ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Langer R ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Anderson DG ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); Jacks T ( David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139); |
| Abstract | MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 34 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Lung Neoplasms Therapy MicroRNAs Therapeutic Use RNA, Small Interfering Adenocarcinoma Genetics Metabolism Animals Antineoplastic Agents Administration & Dosage Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Cisplatin Combined Modality Therapy Gene Expression MAP Kinase Signaling System Mice Mice, Knockout Mice, Transgenic Mutation Nanoparticles Nanotechnology Proto-Oncogene Proteins Proto-Oncogene Proteins P21(ras) RNA, Neoplasm Tumor Suppressor Protein P53 Deficiency Ras Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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