title: Oncolytic reovirus synergizes with chemotherapeutic agents to promote cell death in canine mammary gland tumor.
abstract: The oncolytic effects of reovirus in various cancers have been proven in many clinical trials in human medicine. Oncolytic virotherapy using reovirus for canine cancers is being developed in our laboratory. The objective of this study was to examine the synergistic anti-cancer effects of a combination of reovirus and low doses of various chemotherapeutic agents on mammary gland tumors (MGTs) in dogs. The first part of this study demonstrated the efficacy of reovirus in canine MGTs in vitro and in vivo. Reovirus alone exerted significant cell death by means of caspase-dependent apoptosis in canine MGT cell lines. A single injection of reovirus impeded growth of canine MGT tumors in xenografted mice, but was insufficient to induce complete tumor regression. The second part of this study highlighted the anti-tumor effects of reovirus in combination with low doses of paclitaxel, carboplatin, gemcitabine, or toceranib. Enhanced synergistic activity was observed in the MGT cell line treated concomitantly with reovirus and in all the chemotherapeutic agents except toceranib. In addition, combining reovirus with paclitaxel or gemcitabine at half dosage of half maximal inhibitory concentration (IC50) enhanced cytotoxicity by activating caspase 3. Our data suggest that the combination of reovirus and low dose chemotherapeutic agents provides an attractive option in canine cancer therapy.
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Masaya
authors.initials: M
authors.lastname: Igase
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Chung Chew
authors.initials: CC
authors.lastname: Hwang
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kambayashi
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Takako Shimokawa
authors.initials: TS
authors.lastname: Miyama
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Kenji
authors.initials: K
authors.lastname: Baba
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Masaru
authors.initials: M
authors.lastname: Okuda
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics (Igase, Noguchi, Mizuno), Laboratory of Veterinary Internal Medicine (Kambayashi, Miyama, Baba, Okuda), and Laboratory of Veterinary Pathology (Kubo), Joint Faculty of Veterinary Medicine and Laboratory of Molecular Diagnostics and Therapeutics (Hwang) and Biomedical Science Center for Translational Research (Okuda, Noguchi, Mizuno), United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan; Oncolytics Biotech Inc., Calgary, Alberta (Coffey).
authors.forename: Takuya
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental; D050504:Oncolytic Viruses; D012087:Reoviridae
chemical_list: D000970:Antineoplastic Agents