Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

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• 作者：Tetsuo Fujita ; Takefumi Satoh ; Terry L. Timme ; Takahiro Hirayama ; Julie X. Zhu ; Nobuyuki Kusaka ; Koji Naruishi ; Guang Yang ; Alexei Goltsov ; Jianxiang Wang ; Maria T. Vlachaki ; Bin S. Teh ; E. Brian Butler ; Timothy C. Thompson
• 关键词：GLIPR1 ; Gene therapy ; Radiation therapy ; Bladder cancer ; Prostate cancer
• 刊名：Urologic Oncology: Seminars and Original Investigations
• 出版年：February, 2014
• 年：2014
• 卷：32
• 期：2
• 页码：92-100
• 全文大小：921 K

文摘

Objectives

The objectives of this study are to explore the potential benefits of combining AdGlipr1 (or AdGLIPR1) gene therapy with radiotherapy using subcutaneous prostate and bladder cancer models.

Materials and methods

Combination adenoviral vector-mediated gene therapy and radiotherapy were applied to 178-2 BMA and TSU-Pr1 cells in vitro and colony formation and apoptosis were analyzed. In addition, combination therapies were administered to mice bearing subcutaneous 178-2 BMA and TSU-Pr1 tumors, and tumor growth suppression and survival extension were compared with the monotherapies (AdGlipr1/AdGLIPR1 and radiotherapy) or control vector Adv/CMV/尾gal, as well as single-cycle treatment with 2-cycle treatment.

Results

Combination treatment significantly suppressed colony formation and increased apoptosis in vitro. In vivo, combination therapy produced significant 178-2 BMA and TSU-Pr1 tumor growth suppression and survival extension compared with the monotherapies or the control. Further tumor growth suppression and survival extension were observed after 2 cycles of the combination treatment.

Conclusions

Combining AdGlipr1 (AdGLIPR1) with radiotherapy may achieve additive or synergistic tumor control in selected prostate and bladder tumors, and additional therapeutic effects may result with repeated treatment cycles.