Abstract
Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes.
Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.
Keywords: Retinoblastoma, RB, p130, p53, tumor suppressor gene, microbubbles, ultrasound, systemic targeted viral gene delivery, radiation, external beam radiation, apoptosis induction, prostate cancer.
Current Gene Therapy
Title:Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer
Volume: 13 Issue: 3
Author(s): Rounak Nande, Adelaide Greco, Michael S. Gossman, Jeffrey P. Lopez, Luigi Claudio, Marco Salvatore, Arturo Brunetti, James Denvir, Candace M. Howard and Pier Paolo Claudio
Affiliation:
Keywords: Retinoblastoma, RB, p130, p53, tumor suppressor gene, microbubbles, ultrasound, systemic targeted viral gene delivery, radiation, external beam radiation, apoptosis induction, prostate cancer.
Abstract: Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes.
Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.
Export Options
About this article
Cite this article as:
Nande Rounak, Greco Adelaide, Gossman Michael S., Lopez Jeffrey P., Claudio Luigi, Salvatore Marco, Brunetti Arturo, Denvir James, Howard Candace M. and Claudio Pier Paolo, Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer, Current Gene Therapy 2013; 13 (3) . https://dx.doi.org/10.2174/1566523211313030001
DOI https://dx.doi.org/10.2174/1566523211313030001 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations
Current Genomics Molecular Markers of Angiogenesis and Metastasis in Lines of Oral Carcinoma after Treatment with Melatonin
Anti-Cancer Agents in Medicinal Chemistry Challenges and Persistent Questions in the Treatment of Trichomoniasis
Current Topics in Medicinal Chemistry Dimerization and Ion Binding Properties of S100P Protein
Protein & Peptide Letters Oncogenic MicroRNA-27a is a Target for Genistein in Ovarian Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry mRNA as a Versatile Tool for Exogenous Protein Expression
Current Gene Therapy Impact of Environmental Endocrine Disruption on the Reproductive System for Human Health
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Regulation of Death and Growth Signals at the Plasma Membrane by Sphingomyelin Synthesis: Implications for Hematological Malignancies
Recent Patents on Anti-Cancer Drug Discovery The Modulation of Inter-Organelle Cross-Talk to Control Apoptosis
Medicinal Chemistry Polo-like Kinase 1-targeting Chitosan Nanoparticles Suppress the Progression of Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Toxicogenomics
Current Drug Metabolism Transglutaminase-Mediated Activation of Nuclear Transcription Factor-κB in Cancer Cells: A New Therapeutic Opportunity
Current Cancer Drug Targets Editorial (Thematic Issue: Targeting Epithelial-to-Mesenchymal Transition for Cancer Therapy)
Current Pharmaceutical Design Meet Our Editorial Board Member:
Current Cancer Drug Targets Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and other Hematologic and Solid Malignancies
Current Cancer Drug Targets Overview of Development and Formulation of <sup>177</sup>Lu-DOTA-TATE for PRRT
Current Radiopharmaceuticals Role of Prolyl Endopeptidase in Intracellular Transport and Protein Secretion
CNS & Neurological Disorders - Drug Targets Does Ligand Symmetry Play a Role in the Stabilization of DNA G-Quadruplex Host-Guest Complexes?
Current Medicinal Chemistry Editorial (Thematic Issue: PET/CT in External Beam Radiation Therapy Dose Planning)
Current Radiopharmaceuticals Peptides as Carrier for Tumor Diagnosis and Treatment
Current Medicinal Chemistry - Anti-Cancer Agents