title: Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models.
abstract: OBJECTIVE
  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.
  
  
  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/βgal, 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.
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX.
authors: Tetsuo
authors: T
authors: Fujita
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX.
authors: Takefumi
authors: T
authors: Satoh
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX; Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.
authors: Terry L
authors: TL
authors: Timme
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Takahiro
authors: T
authors: Hirayama
authors: Department of Radiology, Baylor College of Medicine, Houston, TX.
authors: Julie X
authors: JX
authors: Zhu
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX.
authors: Nobuyuki
authors: N
authors: Kusaka
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX.
authors: Koji
authors: K
authors: Naruishi
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Guang
authors: G
authors: Yang
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Alexei
authors: A
authors: Goltsov
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Jianxiang
authors: J
authors: Wang
authors: Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; Department of Radiology, Baylor College of Medicine, Houston, TX.
authors: Maria T
authors: MT
authors: Vlachaki
authors: Department of Radiology, Baylor College of Medicine, Houston, TX.
authors: Bin S
authors: BS
authors: Teh
authors: Department of Radiology, Baylor College of Medicine, Houston, TX.
authors: E
authors: E
authors: Brian Butler
authors: Scott Department of Urology, Baylor College of Medicine, Houston, TX; Department of Radiology, Baylor College of Medicine, Houston, TX; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX. Electronic address: timthomp@mdanderson.org.
authors: Timothy C
authors: TC
authors: Thompson
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy / Q000379:methods*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000235:genetics / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: C094538:GLIPR1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins
keywords: Bladder cancer; GLIPR1; Gene therapy; Prostate cancer; Radiation therapy