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Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis.
Vennin, Claire; Chin, Venessa T; Warren, Sean C; Lucas, Morghan C; Herrmann, David; Magenau, Astrid; Melenec, Pauline; Walters, Stacey N; Del Monte-Nieto, Gonzalo; Conway, James R W; Nobis, Max; Allam, Amr H; McCloy, Rachael A; Currey, Nicola; Pinese, Mark; Boulghourjian, Alice; Zaratzian, Anaiis; Adam, Arne A S; Heu, Celine; Nagrial, Adnan M; Chou, Angela; Steinmann, Angela; Drury, Alison; Froio, Danielle; Giry-Laterriere, Marc; Harris, Nathanial L E; Phan, Tri; Jain, Rohit; Weninger, Wolfgang; McGhee, Ewan J; Whan, Renee; Johns, Amber L; Samra, Jaswinder S; Chantrill, Lorraine; Gill, Anthony J; Kohonen-Corish, Maija; Harvey, Richard P; Biankin, Andrew V; Evans, T R Jeffry; Anderson, Kurt I; Grey, Shane T; Ormandy, Christopher J; Gallego-Ortega, David; Wang, Yingxiao; Samuel, Michael S; Sansom, Owen J; Burgess, Andrew; Cox, Thomas R; Morton, Jennifer P; Pajic, Marina.
Afiliação
  • Vennin C; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Chin VT; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Warren SC; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Lucas MC; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Herrmann D; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Magenau A; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Melenec P; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Walters SN; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Del Monte-Nieto G; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Conway JR; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Nobis M; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Allam AH; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • McCloy RA; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Currey N; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Pinese M; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Boulghourjian A; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Zaratzian A; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Adam AA; Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Heu C; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Nagrial AM; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Chou A; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Steinmann A; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Drury A; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Froio D; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Giry-Laterriere M; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Harris NL; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Phan T; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Jain R; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Weninger W; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • McGhee EJ; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Whan R; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Johns AL; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Samra JS; Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Chantrill L; Biomedical Imaging Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Gill AJ; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Kohonen-Corish M; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Harvey RP; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Biankin AV; Department of Pathology, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia.
  • Evans TR; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Anderson KI; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Grey ST; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Ormandy CJ; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Gallego-Ortega D; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Wang Y; Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales 2522, Australia.
  • Samuel MS; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
  • Sansom OJ; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Burgess A; Immune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Cox TR; University of Sydney Medical School, Sydney, New South Wales 2006, Australia.
  • Morton JP; Immune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Pajic M; University of Sydney Medical School, Sydney, New South Wales 2006, Australia.
Sci Transl Med ; 9(384)2017 04 05.
Article em En | MEDLINE | ID: mdl-28381539
The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Progressão da Doença / Inibidores de Proteínas Quinases / Quinases Associadas a rho Tipo de estudo: Diagnostic_studies Limite: Animals / Humans Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Progressão da Doença / Inibidores de Proteínas Quinases / Quinases Associadas a rho Tipo de estudo: Diagnostic_studies Limite: Animals / Humans Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália