Antitumor Activity of Sustained N-Myc Reduction in Rhabdomyosarcomas and Transcriptional Block by Antigene Therapy

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  • Roberto Tonelli
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Alan McIntyre
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Consuelo Camerin
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Zoë S. Walters
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Korinne Di Leo
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Joanna Selfe
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Stefania Purgato
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Edoardo Missiaglia
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Andrea Tortori
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Jane Renshaw
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Annalisa Astolfi
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Kathryn R. Taylor
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Salvatore Serravalle
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Ryan Bishop
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Cristina Nanni
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Linda J. Valentijn
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Andrea Faccini
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Ivo Leuschner
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Serena Formica
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Jorge S. Reis-Filho
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Valentina Ambrosini
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Khin Thway
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Monica Franzoni
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Brenda Summersgill
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Rosangela Marchelli
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Patrizia Hrelia
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Giorgio Cantelli-Forti
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Stefano Fanti
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Roberto Corradini
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Andrea Pession
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom
  • Janet Shipley
    Authors' Affiliations: Departments of 1Pediatric Hematology and Oncology and 2Pharmacology, University of Bologna; 3Department of Nuclear Medicine, University of Bologna, S. Orsola Hospital, Bologna, Italy; 4Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics and 5Pediatric Oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 6Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Department of Organic and Industrial Chemistry, University of Parma, Parma, Italy; 8Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany; 9Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories; and 10Department of Histopathology, Royal Marsden NHS Trust, London, United Kingdom

説明

<jats:title>Abstract</jats:title> <jats:p>Purpose: Rhabdomyosarcomas are a major cause of cancer death in children, described with MYCN amplification and, in the alveolar subtype, transcription driven by the PAX3-FOXO1 fusion protein. Our aim was to determine the prevalence of N-Myc protein expression and the potential therapeutic effects of reducing expression in rhabdomyosarcomas, including use of an antigene strategy that inhibits transcription.</jats:p> <jats:p>Experimental Design: Protein expression was assessed by immunohistochemistry. MYCN expression was reduced in representative cell lines by RNA interference and an antigene peptide nucleic acid (PNA) oligonucleotide conjugated to a nuclear localization signal peptide. Associated gene expression changes, cell viability, and apoptosis were analyzed in vitro. As a paradigm for antigene therapy, the effects of systemic treatment of mice with rhabdomyosarcoma cell line xenografts were determined.</jats:p> <jats:p>Results: High N-Myc levels were significantly associated with genomic amplification, presence of the PAX3/7-FOXO1 fusion genes, and proliferative capacity. Sustained reduction of N-Myc levels in all rhabdomyosarcoma cell lines that express the protein decreased cell proliferation and increased apoptosis. Positive feedback was shown to regulate PAX3-FOXO1 and N-Myc levels in the alveolar subtype that critically decrease PAX3-FOXO1 levels on reducing N-Myc. Pharmacologic systemic administration of the antigene PNA can eliminate alveolar rhabdomyosarcoma xenografts in mice, without relapse or toxicity.</jats:p> <jats:p>Conclusion: N-Myc, with its restricted expression in non-fetal tissues, is a therapeutic target to treat rhabdomyosarcomas, and blocking gene transcription using antigene oligonucleotide strategies has therapeutic potential in the treatment of cancer and other diseases that has not been previously realized in vivo. Clin Cancer Res; 18(3); 796–807. ©2011 AACR.</jats:p>

収録刊行物

  • Clinical Cancer Research

    Clinical Cancer Research 18 (3), 796-807, 2012-01-31

    American Association for Cancer Research (AACR)

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