New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin

New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin
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DOI:
10.1007/s00280-007-0553-1
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发表时间:
2008-05-01
影响因子:
3
通讯作者:
Kaneda, Yasufumi
Kaneda, Yasufumi
中科院分区:
医学3区
文献类型:
--
作者:
Kawano, Hirokazu;Komaba, Shintaro;Kaneda, Yasufumi

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目的探讨盐酸多柔比星(DXR)联合日本血凝病毒包膜载体(HVJ-E)对小鼠膀胱癌的治疗作用,为建立一种新的治疗膀胱癌的方法提供实验依据。在肿瘤植入后第14天通过膀胱的组织学分析来评价组合疗法的抗肿瘤效果。在单次或两次单独给予DXR或DXR/HVJ-E后,检查MB 49播散小鼠的存活率60天。结果HVJ-E联合DXR膀胱灌注组的无瘤率(11/21)明显高于单纯DXR组(3/19)(P < 0.05)。HVJ-E联合DXR膀胱灌注组的中位生存期> 60天,而单纯DXR膀胱灌注组的中位生存期为29天(P < 0.05)。结论HVJ-E与化疗药物DXR联合应用可增强小鼠的抗肿瘤作用。抗肿瘤免疫似乎使用HVJ-E增强。
Purpose 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.