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1615 Poydras Street - Suite 1000
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 Cherie Ann Nathan, MD
Areas of Research: Cancer Virotherapy The eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in a variety of solid tumors and in particular in all HNSCC. The biologic importance of eIF4E in HNSCC is underscored by the finding that eIF4E overexpression in surgical margins increases the risk of recurrence by 6.5 fold compared to patients with eIF4E negative margins and is an independent risk factor for recurrence. This was compared to p53 overexpression in the margins and found to be a more sensitive marker for recurrence. When eIF4E, the protein translation factor, is overexpressed in HNSCC it increases the translation of weak mRNAs two of which have been found to be potent angiogenic factors b-FGF and VEGF. In an earlier study an episomal vector containing antisense RNA to eIF4E reduced the level of eIF4E in a HNSCC cell line and suppressed both the tumorigenic and angiogenic properties of the cells as demonstrated by loss of capacity to grow in soft agar, reduced expression of angiogenic factors and loss of tumorigenicity in nude mice (DeFatta, Laryngosopce 2000). We intend to decrease the recurrence rate in this group of patients with eIF4E positive margins with a eIF4E antisense adenovirus vector thus decreasing the potential conversion of these occult cells into the malignant phenotype. Our goal is to establish eIF4E antisense adenoviral vectors, demonstrate that this vector suppresses the growth of established tumors of the head and neck in cell culture and in animal models, and finally to develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients. Selected Publications Nathan, C.A., Amirghahari, N., Rong, X., Giordano, T., Sibley, D., Nordberg, M., Glass, J., Agarwal, A., and Caldito, G. mTOR inhibitors as possible adjuvant therapy for microscopic residual disease in Head and Neck Squamous Cell Cancer. Cancer Research, (2007) Ye, G., Burton, G.V., Nathan, C.A., and Ampil, F.L. Squamous cell carcinoma of the oral cavity following breast cancer treatment. Southern Medical Journal, (2006) 99(10): 1150-1151 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) McDuffie, C.M., Amirghahari, N., Caldito, G., Lian, T.S., Thompton, L., and Nathan, C.A. Predictive factors for proterior triangle metastasis in HNSCC. Laryngoscope, (2005) December; 115(12): 2114-2117 Lee, M., Ramaswamy, M.R., Lilien, D.L., Nathan, C.A. Unilateral vocal cord paralysis causes contralateral false-positive positron emission tomography scans of the larynx. Annuals of Otol Rhinol Laryngol, (2005) March; 114(3): 202-206 |
