Improvement of the tumor-suppressive effect of boron neutron capture therapy for amelanotic melanoma by intratumoral injection of the tyrosinase gene.
Boron neutron capture therapy (BNCT) is successful when there is a sufficient (10)B concentration in tumor cells. In melanoma, (10)B-para-boronophenylalanine (BPA) accumulation is proportional to melanin-producing activity. This study was done to confirm enhancement of the tumor-suppressive effect of BNCT on amelanotic melanoma by intratumoral injection of the tyrosinase gene. D178 or FF amelanotic melanomas were implanted s.c. in Syrian hamsters. One group of D178- or FF-bearing hamsters (TD178 or TFF group) received intratumoral injections of pcDNA-Tyrs constructed as a tyrosinase expression plasmid. The other hamsters (pD178 and pFF groups) were injected with pUC119, and control hamsters (D178 and FF groups) only with transfection reagents. All the groups underwent immunofluorescence analysis of tyrosinase expression and BPA biodistribution studies. BNCT experiments were done at the Kyoto University Research Reactor. Tyrosinase expression increased in the tumors of the TD178 and TFF groups but remained the same in the pD178 and pFF groups. Tumor boron concentrations in the TD178 and TFF groups increased significantly (TD178: 49.7 +/- 12.6 versus D178: 27.2 +/- 4.9 microg/g, P < 0.0001; TFF: 30.7 +/- 6.6 versus FF: 13.0 +/- 4.7 microg/g, P < 0.0001). The BNCT tumor-suppressive effect was marked in the TD178 and TFF groups. In vivo transfection with the tyrosinase gene increased BPA accumulation in the tumors, the BNCT tumor-suppressive effect on amelanotic melanoma being significantly enhanced. These findings suggest a potential new clinical strategy for the treatment of amelanotic melanoma with BNCT.
Department of Radiation Oncology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192 Okayama, Japan. moriden@med.kawasaki-m.ac.jp
Norimasa
N
Morita
Junichi
J
Hiratsuka
Hirohumi
H
Kondoh
Masako
M
Uno
Tomoyuki
T
Asano
Yoko
Y
Niki
Yoshinori
Y
Sakurai
Koji
K
Ono
Tamotsu
T
Harada
Yoshinari
Y
Imajo
D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D048708:Cell Growth Processes / Q000235:genetics / Q000528:radiation effects; D003131:Combined Modality Therapy; D006224:Cricetinae; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D015552:Injections, Intralesional; D018328:Melanoma, Amelanotic / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D008647:Mesocricetus; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D014018:Tissue Distribution; D014162:Transfection
D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D014442:Monophenol Monooxygenase; C033685:4-boronophenylalanine