Evaluation of hyperbaric oxygen as a chemosensitizer in the treatment of epithelial ovarian cancer in xenografts in mice.
BACKGROUND
Resistance to chemotherapy is common in bulky hypoxic tumors such as epithelial ovarian cancer. Hyperbaric oxygen (HBO) oxygenates hypoxic tissues and promotes neovascularization. These unique properties of HBO may help overcome chemotherapy resistance by increasing both tumor perfusion and cellular sensitivity. This study was undertaken to determine if HBO increases the response of epithelial ovarian cancer to cisplatin chemotherapy.


METHODS
In Phase I, 64 nu/nu mice were divided into four groups and subcutaneously inoculated with cells from the A2780 human epithelial ovarian cancer cell line. Group 1 served as controls. Group 2 received weekly intraperitoneal cisplatin (3.15 mg/kg). Group 3 was exposed to HBO (dives) at 2.4 atmospheres absolute pressure for 90 minutes, 7 days a week. Group 4 received both cisplatin and HBO. In Phase II, 72 mice were divided into two groups and similarly inoculated. Both groups received weekly intraperitoneal cisplatin (2.5 mg/kg). Group 1 was not exposed to HBO. Group 2 was exposed to HBO for 5 days a week.


RESULTS
Dramatic tumor neovascularization was found in tumors of mice exposed to HBO (P = 0.0001). There was significant (P = 0.014) tumor growth retardation in Phase I for mice receiving both cisplatin and HBO compared with those treated with cisplatin alone. This significance was noted after just two doses of cisplatin but subsequently lost due to reduced numbers of mice. In Phase II, neovascularization was detectable after 10 HBO treatments (2 weeks) and was maximal after 15 treatments (3 weeks).


CONCLUSIONS
Hyperbaric oxygen increases vascularity in bulky tumors such as epithelial ovarian cancer. There appears to be a relationship between increased vascularity and enhanced response to chemotherapy that merits further investigation.
Alagoz
T
T
Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Buller
R E
RE
Anderson
B
B
Terrell
K L
KL
Squatrito
R C
RC
Niemann
T H
TH
Tatman
D J
DJ
Jebson
P
P
D000818:Animals; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004351:Drug Resistance; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D006931:Hyperbaric Oxygenation; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008938:Mitosis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002945:Cisplatin