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
-
Psychological Factors Associated with Response to Treatment in Rheumatoid Arthritis
Current Pharmaceutical Design Molecular Mechanisms Underlying Psychological Stress and Cancer
Current Pharmaceutical Design Role of Nuclear Imaging in Cardiac Amyloidosis Management: Clinical Evidence and Review of Literature
Current Medical Imaging Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway
Current Molecular Pharmacology Editorial
Recent Patents on Anti-Cancer Drug Discovery Development of Dry Powder Inhalers
Recent Patents on Drug Delivery & Formulation Recent Progress in Phosphoinositide 3-Kinases: Oncogenic Properties and Prognostic and Therapeutic Implications
Current Protein & Peptide Science Antiproliferative and Antioxidant Potential of Leaf and Leaf Derived Callus Extracts of Aerva lanata (L.) Juss. Ex Schult. Against Human Breast Cancer (MCF-7) Cell Lines
The Natural Products Journal The Janus Face of Cathelicidin in Tumorigenesis
Current Medicinal Chemistry Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer’s Dementia: Possible Mechanisms, Current Evidence and Future Directions
Current Alzheimer Research Eupatilin Inhibits the Proliferation and Migration of Prostate Cancer Cells through Modulation of PTEN and NF-κB Signaling
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Current Drug Targets Pre-Clinical and Clinical Evaluation of Nuclear Tracers for the Molecular Imaging of Vulnerable Atherosclerosis: An Overview
Current Medicinal Chemistry Novel Biomarkers Assessing the Calcium Deposition in Coronary Artery Disease
Current Medicinal Chemistry Novel N-mustard-benzimidazoles/benzothiazoles Hybrids, Synthesis and Anticancer Evaluation
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Regulation of Epithelial-Mesenchymal Transition by Hypoxia in Cancer: Targets and Therapy
Current Pharmaceutical Design Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer
Current Pharmaceutical Design Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Current Cancer Drug Targets Use of the Semiconductor Nanotechnologies “Quantum Dots” for in vivo Cancer Imaging
Recent Patents on Anti-Cancer Drug Discovery Editorial [Hot Topic: SOD Enzymes and Their Mimics in Cancer: Pro- vs Anti-Oxidative Mode of Action-Part I (Guest Editor: Ines Batinic-Haberle)]
Anti-Cancer Agents in Medicinal Chemistry