Effectiveness of combined modality radiotherapy of orthotopic human squamous cell carcinomas in Nu/Nu mice using cetuximab, tirapazamine and MnSOD-plasmid liposome gene therapy.

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.
AuthorsMichael W Epperly, Stephen Y Lai, Anthony J Kanai, Neal Mason, Brian Lopresi, Tracey Dixon, Darcy Franicola, Yunyun Niu, William R Wilson, Joel S Greenberger
JournalIn vivo (Athens, Greece) (In Vivo) 2010 Jan-Feb Vol. 24 Issue 1 Pg. 1-8 ISSN: 0258-851X [Print] Greece
PMID20133969 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Liposomes
  • Radiation-Sensitizing Agents
  • Triazines
  • tirapazamine
  • Nitric Oxide
  • Superoxide Dismutase
  • Cetuximab
  • Animals
  • Antibodies, Monoclonal (administration & dosage)
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Carcinoma, Squamous Cell (metabolism, pathology, therapy)
  • Cell Line, Tumor
  • Cetuximab
  • Dose-Response Relationship, Radiation
  • Genetic Therapy
  • Humans
  • Liposomes
  • Mice
  • Mice, Nude
  • Mouth Neoplasms (metabolism, pathology, therapy)
  • Nitric Oxide (metabolism)
  • Radiation-Sensitizing Agents (administration & dosage)
  • Radiotherapy, Adjuvant
  • Superoxide Dismutase (genetics)
  • Triazines (administration & dosage)
  • Xenograft Model Antitumor Assays

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