New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin.
OBJECTIVE
To establish a new therapeutic method to treat bladder carcinoma, we investigated the therapeutic potential of doxorubicin hydrochloride (DXR) combined with hemagglutinating virus of Japan-envelope vector (HVJ-E) in an orthotropic mouse bladder cancer model.


METHODS
DXR and/or HVJ-E were instilled into the bladder after implantation of MB49 cells. Antitumor effects of combination therapy were evaluated by histological analysis of the bladder on day 14 after tumor implantation. The survival rate of MB49-disseminated mice was examined for 60 days after single or double administration of DXR alone or DXR/HVJ-E. The surviving mice were re-challenged with intravesical injection of MB49 cells, and the bladder was observed after 3 weeks.


RESULTS
Combined intravesical instillation of HVJ-E and DXR resulted in a significantly higher rate of tumor-free mice (11/21) compared with mice treated using DXR alone (3/19, P<0.05). Median survival was >60 days for intravesical instillation of HVJ-E and DXR, compared with the 29 days for DXR instillation alone (P<0.05). After combination therapy, surviving mice formed no tumors in the bladder following intravesical re-instillation of MB49.


CONCLUSIONS
HVJ-E increased antitumor effects in combination with chemotherapeutic agent (DXR). Antitumor immunity appeared to be enhanced using HVJ-E.
Kawano
Hirokazu
H
Saito Institute for Drug Discovery, Research and Development, Genomidea Inc., Ibaraki, Osaka, Japan.
Komaba
Shintaro
S
Yamasaki
Tsugiko
T
Maeda
Mitsuyo
M
Kimura
Yoshimitsu
Y
Maeda
Akito
A
Kaneda
Yasufumi
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D029082:Sendai virus / Q000737:chemistry*; D016019:Survival Analysis; D013778:Tetrazolium Salts / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014759:Viral Envelope Proteins / Q000737:chemistry*
C476329:2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt; D000903:Antibiotics, Antineoplastic; D013778:Tetrazolium Salts; D014759:Viral Envelope Proteins; D004317:Doxorubicin