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

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.
Authors	Michael W Epperly, Stephen Y Lai, Anthony J Kanai, Neal Mason, Brian Lopresi, Tracey Dixon, Darcy Franicola, Yunyun Niu, William R Wilson, Joel S Greenberger
Journal	In vivo (Athens, Greece) (In Vivo) 2010 Jan-Feb Vol. 24 Issue 1 Pg. 1-8 ISSN: 0258-851X [Print] Greece
PMID	20133969 (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
Topics	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) Tirapazamine Triazines (administration & dosage) Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!