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Pier Paolo Claudio, M.D., Ph.D. Awarded Two Grants

July 29, 2009

Pier Paolo Claudio, M.D., Ph.D.
Associate Professor
Department of Biochemistry and Microbiology &
Department of Surgery,
Joan C. Edwards School of Medicine
Marshall University
R.C. Byrd Biotech Science Center

1. Awarded R-21 grant from NIH (CA131395)

The grant title is: Ultrasound guided site-specific gene delivery in prostate cancer

This proposal aims at improving the efficiency and specificity of gene delivery in prostate cancer (PC) by using an innovative system consisting of ultrasound contrast agents, viral vectors and ultrasound waves. Additionally, this proposal aims at improving the response of prostate cancer to radiation therapy. Despite the progress of modern radiation techniques in largely improving the prognosis of patients with prostate adenocarcinoma, the maximum benefit that can be achieved with conventional radiation therapy has probably been reached. The impact of this proposal lies in the fact that a gene such as p130 significantly increases the percentage of apoptotic cells after γ- irradiation potentially improving the treatment of prostate cancer. Additionally, ultrasound contrast agents offer the advantage of targeted gene release, thereby improving its specificity. The impact of microbubbles on gene therapy is to protect the viral vectors from rapid degradation by the immune system thus allowing for intravenous injection rather than direct target organ injection. Additionally, viruses are non-specific. Ultrasound contrast agents (microbubbles) may be designed to serve as safe vehicles to encapsulate and deliver genetic materials. The gas filled microspheres effectively lower the energy threshold for cavitation. This allows diagnostic transducers operating within the energy levels mandated by the FDA to be used for drug/gene delivery. In the sonification zone the microbubbles undergo cavitation, destroying the bubbles and releasing their contents. Cavitation also creates small shockwaves that increase cell permeability. This has been shown to increase transcapillary passage of macromolecules or nanoshperes codelivered by the microbubbles in experimental animals.

In conclusion, this proposal aims at improving the outcome of radiation therapy in prostate cancer. The outcome of these studies will demonstrate whether targeted p130 gene delivery is an effective adjuvant treatment in the therapy of prostate adenocarcinoma and whether its use could be directed at decreasing treatment-related morbidity. The results of these experiments will be the basis for future patient clinical trials.

2. Laboratory has been awarded an R03 grant (CA140024) from NIH.

The grant title is: Ultrasound-guided gene delivery in pancreatic cancer

The present study seeks to develop an effective therapy for pancreatic cancer employing cancer-specific apoptosis-inducing cytokines such as IFN-γ or mda-7/IL-24, delivered by a conditionally replication competent adenovirus, a cancer terminator virus (CTV), in combination with ultrasound contrast agents and ultrasound waves. This novel approach will permit efficient systemic delivery of the CTV to tumors, offering the potential to develop a ‘cure’ for both localized and metastatic pancreatic cancer.
Successful achievement of the objectives of the present proposal will provide for rapid translation into the clinic as a new and potentially effective therapy for metastatic pancreatic cancer.

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