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Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen.
Dassie, Justin P; Hernandez, Luiza I; Thomas, Gregory S; Long, Matthew E; Rockey, William M; Howell, Craig A; Chen, Yani; Hernandez, Frank J; Liu, Xiu Ying; Wilson, Mary E; Allen, Lee-Ann; Vaena, Daniel A; Meyerholz, David K; Giangrande, Paloma H.
Afiliación
  • Dassie JP; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Hernandez LI; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Thomas GS; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Long ME; 1] Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA [2] Inflammation Program, University of Iowa, Iowa City, Iowa, USA.
  • Rockey WM; Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA.
  • Howell CA; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Chen Y; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Hernandez FJ; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Liu XY; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Wilson ME; 1] Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA [2] Department of Microbiology, University of Iowa, Iowa City, Iowa, USA [3] Veteran's Affairs Medical Center, University of Iowa, Iowa City, Iowa, USA.
  • Allen LA; 1] Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA [2] Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA [3] Inflammation Program, University of Iowa, Iowa City, Iowa, USA [4] Department of Microbiology, University of Iowa, Iowa City, Iowa, US
  • Vaena DA; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
  • Meyerholz DK; Department of Pathology, University of Iowa, Iowa City, Iowa, USA.
  • Giangrande PH; 1] Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA [2] Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA [3] Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA.
Mol Ther ; 22(11): 1910-22, 2014 Nov.
Article en En | MEDLINE | ID: mdl-24954476
Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Glutamato Carboxipeptidasa II / Aptámeros de Nucleótidos / Terapia Molecular Dirigida / Antígenos de Superficie Límite: Animals / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Glutamato Carboxipeptidasa II / Aptámeros de Nucleótidos / Terapia Molecular Dirigida / Antígenos de Superficie Límite: Animals / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos