Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model.
OBJECTIVE
The effect of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on human oral squamous cell carcinoma (SCC) xenografts in nude mice was examined.


METHODS
Tumor-bearing mice were given BPA at a dose of 250 mg/kg body weight. The tumor (10)B concentration 2 h after an injection of BPA was higher than those 1 or 3 h after the injection. Neutron irradiation was performed beginning 1, 2 or 3 h after an injection of BPA and the effects on body weight of the animals, tumor growth, survival of tumor-bearing animals, and histology of tumor and normal tissue were examined. Fragmented nuclear DNA, 5-bromo-2'-deoxyuridine (BrdU), and von Willebrand Factor (vWF) were detected by immunohistochemical staining.


RESULTS
Tumor volumes of untreated control animals increased continuously, whereas those of BNCT-treated animals were markedly decreased. Animals given neutron irradiation 2 h after the injection of BPA survived for a longer period as compared with those given neutron irradiation 1 or 3 h after the injection. BNCT reduced the incorporation of BrdU into tumor cells, and induced the enlargement and vacuolation of tumor cells. Disintegration of blood vessels and dense inflammatory cell infiltration were also observed in the stroma of the tumor, but not surrounding normal tissues.


CONCLUSIONS
These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.
Kamida
Akitoshi
A
Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Osaka, Japan.
Obayashi
Shigeki
S
Kato
Itsuro
I
Ono
Koji
K
Suzuki
Minoru
M
Nagata
Kenji
K
Sakurai
Yoshinori
Y
Yura
Yoshiaki
Y
D000818:Animals; D017209:Apoptosis; D001835:Body Weight / Q000528:radiation effects; D001896:Boron Compounds / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy; D001973:Bromodeoxyuridine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014183:Transplantation, Heterologous
C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine; D001973:Bromodeoxyuridine