title: Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma.
abstract: Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16(INK4A)/p14(ARF) and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies.
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Hudson
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Weir
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moon
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Rozelle
authors.initials: R
authors.lastname: Harvie
authors.affiliation: Department of Anatomical Pathology, Flinders University and SA Pathology, Adelaide, Australia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Klebe
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.affiliation: 1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia [2] Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
authors.forename: Viive M
authors.initials: VM
authors.lastname: Howell
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism; D020128:Inhibitory Concentration 50; D018655:Lymphocyte Count; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005810:Multigene Family; D010641:Phenotype; D051381:Rats
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016207:Cytokines; D005978:Glutathione