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Dexamethasone Increases Cisplatin-Loaded Nanocarrier Delivery and Efficacy in Metastatic Breast Cancer by Normalizing the Tumor Microenvironment.
Martin, John D; Panagi, Myrofora; Wang, Chenyu; Khan, Thahomina T; Martin, Margaret R; Voutouri, Chrysovalantis; Toh, Kazuko; Papageorgis, Panagiotis; Mpekris, Fotios; Polydorou, Christiana; Ishii, Genichiro; Takahashi, Shinichiro; Gotohda, Naoto; Suzuki, Toshiyuki; Wilhelm, Matthew E; Melo, Vinicio Alejandro; Quader, Sabina; Norimatsu, Jumpei; Lanning, Ryan M; Kojima, Motohiro; Stuber, Matthew David; Stylianopoulos, Triantafyllos; Kataoka, Kazunori; Cabral, Horacio.
Afiliación
  • Martin JD; Department of Bioengineering, Graduate School of Engineering , The University of Tokyo , Bunkyo, Tokyo 113-8656 , Japan.
  • Panagi M; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Wang C; Process Systems and Operations Research Laboratory, Department of Chemical and Biomolecular Engineering , University of Connecticut , Storrs , Connecticut 06269 , United States.
  • Khan TT; Department of Bioengineering, Graduate School of Engineering , The University of Tokyo , Bunkyo, Tokyo 113-8656 , Japan.
  • Martin MR; Department of Bioengineering, Graduate School of Engineering , The University of Tokyo , Bunkyo, Tokyo 113-8656 , Japan.
  • Voutouri C; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Toh K; Innovation Center of NanoMedicine , Kawasaki Institute of Industrial Promotion , Kawasaki , Kanagawa 210-0821 , Japan.
  • Papageorgis P; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Mpekris F; Department of Life Sciences, Program in Biological Sciences , European University Cyprus , Nicosia 1516 , Cyprus.
  • Polydorou C; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Ishii G; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Takahashi S; Exploratory Oncology Research & Clinical Trial Center , National Cancer Center , Kashiwa , Chiba 277-8577 , Japan.
  • Gotohda N; Department of Hepatobiliary-Pancreatic Surgery , National Cancer Center Hospital East , Kashiwa , Chiba 277-8577 , Japan.
  • Suzuki T; Department of Hepatobiliary-Pancreatic Surgery , National Cancer Center Hospital East , Kashiwa , Chiba 277-8577 , Japan.
  • Wilhelm ME; Department of Hepatobiliary-Pancreatic Surgery , National Cancer Center Hospital East , Kashiwa , Chiba 277-8577 , Japan.
  • Melo VA; Process Systems and Operations Research Laboratory, Department of Chemical and Biomolecular Engineering , University of Connecticut , Storrs , Connecticut 06269 , United States.
  • Quader S; Innovation Center of NanoMedicine , Kawasaki Institute of Industrial Promotion , Kawasaki , Kanagawa 210-0821 , Japan.
  • Norimatsu J; Innovation Center of NanoMedicine , Kawasaki Institute of Industrial Promotion , Kawasaki , Kanagawa 210-0821 , Japan.
  • Lanning RM; Department of Bioengineering, Graduate School of Engineering , The University of Tokyo , Bunkyo, Tokyo 113-8656 , Japan.
  • Kojima M; Department of Radiation Oncology, School of Medicine , University of Colorado , Aurora , Colorado 80045 , United States.
  • Stuber MD; Exploratory Oncology Research & Clinical Trial Center , National Cancer Center , Kashiwa , Chiba 277-8577 , Japan.
  • Stylianopoulos T; Process Systems and Operations Research Laboratory, Department of Chemical and Biomolecular Engineering , University of Connecticut , Storrs , Connecticut 06269 , United States.
  • Kataoka K; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering , University of Cyprus , Nicosia 1678 , Cyprus.
  • Cabral H; Innovation Center of NanoMedicine , Kawasaki Institute of Industrial Promotion , Kawasaki , Kanagawa 210-0821 , Japan.
ACS Nano ; 13(6): 6396-6408, 2019 06 25.
Article en En | MEDLINE | ID: mdl-31187975
Dexamethasone is a glucocorticoid steroid with anti-inflammatory properties used to treat many diseases, including cancer, in which it helps manage various side effects of chemo-, radio-, and immunotherapies. Here, we investigate the tumor microenvironment (TME)-normalizing effects of dexamethasone in metastatic murine breast cancer (BC). Dexamethasone normalizes vessels and the extracellular matrix, thereby reducing interstitial fluid pressure, tissue stiffness, and solid stress. In turn, the penetration of 13 and 32 nm dextrans, which represent nanocarriers (NCs), is increased. A mechanistic model of fluid and macromolecule transport in tumors predicts that dexamethasone increases NC penetration by increasing interstitial hydraulic conductivity without significantly reducing the effective pore diameter of the vessel wall. Also, dexamethasone increases the tumor accumulation and efficacy of ∼30 nm polymeric micelles containing cisplatin (CDDP/m) against murine models of primary BC and spontaneous BC lung metastasis, which also feature a TME with abnormal mechanical properties. These results suggest that pretreatment with dexamethasone before NC administration could increase efficacy against primary tumors and metastases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dexametasona / Portadores de Fármacos / Cisplatino / Nanopartículas / Neoplasias Mamarias Experimentales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: ACS Nano Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dexametasona / Portadores de Fármacos / Cisplatino / Nanopartículas / Neoplasias Mamarias Experimentales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: ACS Nano Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos