Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal gene therapy reduction of irradiation-induced inflammatory cytokines does not protect orthotopic Lewis lung carcinomas.
BACKGROUND
Intratracheal injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction or fractionated irradiation of C57BL/6J mouse lung has been demonstrated to protect the lung from irradiation-induced damage.


METHODS
To determine whether irradiation-induced inflammatory cytokine levels influenced the recovery of tumors following single fraction irradiation, mice with orthotopic Lewis Lung Carcinoma (3LL) tumors received MnSOD-PL treatment 24 hours after tumor implantation and 24 hours prior to irradiation. Subgroups were implanted with Alzet pumps continuously replacing levels of inflammatory cytokines over 7 days.


RESULTS
In cytokine-treated mice, there was no detectable significant alteration in radiotherapy-mediated improved survival (tumor regrowth delay) compared to irradiated control mice. Each group of mice that received MnSOD-PL had increased survival compared to irradiated controls.


CONCLUSIONS
These results support the anticipated safety of intrapulmonary MnSOD-PL gene therapy in lung cancer patients for protection of normal lung tissue from irradiation while allowing effective irradiation-mediated tumor control.
Guo
Hongliang
H
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Epperly
Michael W
MW
Bernarding
Michael
M
Nie
Suhua
S
Gretton
Joan
J
Jefferson
Mia
M
Greenberger
Joel S
JS
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007260:Infusion Pumps; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D008081:Liposomes; D008168:Lung / Q000276:immunology / Q000528:radiation effects; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D017564:Radiation Pneumonitis / Q000276:immunology / Q000628:therapy*; D011839:Radiation, Ionizing; D013482:Superoxide Dismutase / Q000235:genetics*; D014132:Trachea; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D008081:Liposomes; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013482:Superoxide Dismutase