Arsenic trioxide enhances radiation response of 9L glioma in the rat brain.
Arsenic trioxide (ATO) at low doses induces leukemia cells to undergo apoptosis and at higher doses causes blood flow to solid tumors to shut down. To determine whether a potential synergistic interaction exists between ATO at the non-toxic dose level in the rat and radiation, the present study was carried out with orthotopic 9L malignant gliomas growing in the brains of rats. Animals died within 50 days of treatment when 12-day-old 9L gliomas growing in the brain of Fischer rats were treated with either the drug alone (8 mg/kg) or radiation alone (25 Gy). In contrast, the overall tumor cure rate exceeded 50% at a follow-up time of 120 days after the combined treatment with radiation and ATO. Long-term surviving animals showed no clinical or disproportionately enhanced histopathological changes in the brain parenchyma. Early changes in tumor physiology showed that the vascular leakage of FITC-dextran conjugates was apparent within 8 h of drug administration. Last, the use of diffusion magnetic resonance imaging as an early surrogate marker of therapeutic efficacy corroborated the effects of drug with and without radiation on brain histology and animal survival.
Kim
Jae Ho
JH
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA. jkim1@hfhs.org
Lew
Young S
YS
Kolozsvary
Andrew
A
Ryu
Samuel
S
Brown
Stephen L
SL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005910:Glioma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D010087:Oxides / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide