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1615 Poydras Street - Suite 1000
New Orleans, LA 70112
504.525.5744 voice
504.525.7787 fax

 

Benjamin Li, MDBenjamin Li, MD


Louisiana State University Health Sciences - Shreveport

Areas of Research: Cancer Virotherapy

Our laboratory investigates the in vitro activity of a suicide gene therapy regimen against the rat model Mat BIII breast cancer and CRL-1677 small intestine adenocarcinoma cell line. The eukaryotic translation initiation factor 4E (eIF4E), facilitates the translation of mRNAs with long 5” un-translated regions (UTRs) and thus regulates protein synthesis. This protein has been found in elevated quantities in breast, colon, and head and neck cancers. To exploit this dysfunction, the 619 base pair 5’UTR of FGF-1 was spliced upstream of the herpes simplex virus thymidine kinase gene in the adenovirus vector (Ad-HSV-UTK), with the expectation that TK will be expressed in cells which overexpress eIF4E, and thus yield these cells susceptible to gancyclovir. Gancyclovir selectively kill cells that carry its respective marker, HSV-UTK. 

By splicing a 5’UTR upstream of HSV-TK, thymidine kinase expression was detected in the CRL 1677 cell line. Marked cytotoxicity was evident in the treatment groups, even at a much lower concentration of gancyclovir. Early events of apoptosis were also evident in the treatment group. Suicide gene therapy targeting the overexpression of eIF4E is effective in inducing apoptosis and cell death in these malignant cell lines.

Selected Publications

Byrnes, K., White, S., Chu, Q., Meschonat, C., Yu, H., Johnson, L.W., DeBenedetti, A., Abreo, F., Turnage, R.H., McDonald J.C., and Li, B.D. High eIF4E, VEGF, and microvessel density in stage I to III breast cancer. Annuals of Surgery, (2006) 243(5):683-690

Mathis, J.M., Williams, B.J., Sibley, D.A., Carroll, J.L., Li, J., Odaka, Y., Barlow, S., Nathan, C.A., Li, B.D., and DeBenedetti, A. Cancer-specific targeting of an adenovirus-delivered herpes simplex virus thymidines kinase suicide gene using translational control. Journal of Gene Medicine, (2006)

Chu, Q.D., Connor, M.S., Lilien, D.L., Johnson, L.W., Turnage, R.H., and Li, B.D. Positron emission tomography (PET) positive thyroid incidentaloma: the risk of malignancy observed in a tertiary referral center. The American Surgeon, (2006) March; 72(3): 272-275

Alassas, M., Chu, Q., Burton, G. V., Ampil, F., Mizell, J., and Li, B.D. Neoadjuvant chemotherapy in stage III breast cancer. The American Surgeon, (2005) June; 71(6): 487-492

Ampil, F.L., Burton, G.V., Li, B.D., Chu, Q.D., Krishnamsetty, R.M., and Caldito, G. Thoracic metastases from breast cancer: a single-institution’s experience. Eur Journal of Gyneacological Oncology, (2005) 26(2): 155-157

McClusky D.R., Chu, Q.D., Yu, H., DeBenedetti, A., Johnson, L.W., Meschonat, C., Turnage, R., McDonal, J.C., Abreo, F., and Li., B.D. A prospective trial on initiation factor 4E (eIF4e) overexpression and cancer recurrence in node-positive breast cancer. Annuals of Surgery, (2005) October; 242(4): 584-590

© 2007 - Louisiana Gene Therapy Research Consortium | Last update: August 20, 2008