title: Biological characterization of soft tissue sarcomas.
abstract: Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-γ (IFN-γ), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas.
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: 1 Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Nagano, Japan ; 2 Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo, Japan ; 3 Sigma-Aldrich Collaboration Laboratory, Rehovot 76100, Israel ; 4 Horiuchi Ladies Clinic, Nagano, Japan ; 5 Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan ; 6 Department of Pathology, Keio University Graduate School of Medicine, Tokyo, Japan ; 7 The International Human Epigenome Consortium (IHEC) and CREST, Japan Science and Technology Agency (JST), Saitama, Japan ; 8 Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan ; 9 The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan ; 10 Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
keywords: Sarcoma; proteasome beta subunit 9/β1i (PSMB9/β1i); retinoblastoma (RB); sarcomagenesis; tumour protein 53 (TP53)