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
-
Biological Role of Formaldehyde, and Cycles Related to Methylation, Demethylation, and Formaldehyde Production
Mini-Reviews in Medicinal Chemistry Driving Cellular Plasticity and Survival Through the Signal Transduction Pathways of Metabotropic Glutamate Receptors
Current Neurovascular Research Membrane Localization of Estrogen Receptors
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Small-molecule Antiviral Agents in Ongoing Clinical Trials for COVID-19
Current Drug Targets Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Targeted – Therapy and Imaging Response: A New Paradigm For Clinical Evaluation?
Reviews on Recent Clinical Trials ThermoTRP Channels in Nociceptors: Taking a Lead from Capsaicin Receptor TRPV1
Current Neuropharmacology Antisense Treatment in Human Prostate Cancer and Melanoma
Current Cancer Drug Targets Mevalonate Pathway and Human Cancers
Current Molecular Pharmacology NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as a Potential Drug Target
Current Drug Targets The Chance of Small Interfering RNAs as Eligible Candidates for a Personalized Treatment of Prostate Cancer
Current Pharmaceutical Biotechnology Phytochemical Informatics and Virtual Screening of Herbs Used in Chinese Medicine
Current Pharmaceutical Design The Central Nervous System as a Promising Target to Treat Diabetes Mellitus
Current Topics in Medicinal Chemistry Small Molecule Inhibitors of Multidrug Resistance Gene (MDR1) Expression: Preclinical Evaluation and Mechanisms of Action
Current Cancer Drug Targets Proteomic Analysis of Mitochondria in Raji Cells Following Exposure to Radiation: Implications for Radiotherapy Response
Protein & Peptide Letters Effective Treatment of Human Lung Cancer by Targeting Tissue Factor with a Factor VII-Targeted Photodynamic Therapy
Current Cancer Drug Targets “Letting the Air In” Can Set the Stage for Tumor Recurrences
Current Cancer Therapy Reviews Current Drug Therapy for Prostate Cancer: An Overview
Current Medicinal Chemistry - Anti-Cancer Agents The Therapeutic Potential of ADAM15
Current Pharmaceutical Design Signaling Pathways Responsible for Cancer Cell Invasion as Targets for Cancer Therapy
Current Cancer Drug Targets