Abstract
Hypoxic regions limit the radiocontrollability of head and neck carcinomas. Whether or not combinations of plasmid/liposome mediated overexpression of normal tissue protective manganese superoxide dismutase (MnSOD), cetuximab (C225), and the hypoxic cytotoxin tirapazamine (TPZ) enhanced radiotherapeutic effects was tested in a CAL-33 orthotopic mouse cheek tumor model. The tumor volume continued to increase in the control (untreated) mice, with a ninefold increase by 10 days when the tumors exceeded 2 cm(3). The mice receiving 14 Gy only showed reduced tumor growth to 3.1+/-0.1 fold at day 10. The mice receiving MnSOD-PL, C225, TPZ plus 14 Gy had the best outcome with 0.7+/-0.1 fold increase in tumor volume by 10 days (p=0.015) compared to irradiation only. The addition of MnSOD-PL, TPZ, and C225 to irradiation optimized the therapeutic ratio for the local control of hypoxic region-containing CAL-33 orthotopic tumors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal, Humanized
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / therapy*
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Cell Line, Tumor
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Cetuximab
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Dose-Response Relationship, Radiation
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Genetic Therapy*
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Humans
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Liposomes
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Mice
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Mice, Nude
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Mouth Neoplasms / metabolism
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Mouth Neoplasms / pathology
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Mouth Neoplasms / therapy*
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Nitric Oxide / metabolism
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Radiation-Sensitizing Agents / administration & dosage
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Radiotherapy, Adjuvant
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Superoxide Dismutase / genetics*
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Tirapazamine
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Triazines / administration & dosage
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Liposomes
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Radiation-Sensitizing Agents
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Triazines
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Tirapazamine
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Nitric Oxide
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Superoxide Dismutase
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Cetuximab