Key Members
J.
Michael Mathis, Ph.D.
Director
Dept. of Cellular Biology and Anatomy
B. Jill Williams, Ph.D.
Associate Director
Dept. of Urology
Arrigo De Benedetti, Ph.D.
Dept. of Biochemistry
Ronald Klein, Ph.D.
Dept. of Pharmacology
Cherie-Ann Nathan, M.D.
Dept. of Otolaryngology
Kate Ryman, Ph.D.
Dept. of Microbiology and Immunology
Francesco Turturro, M.D.
Dept. of Medicine
Wei-Ming Duan, M.D., Ph.D.Dept.
of Cellular Biology and Anatomy
Benjamin Li, M.D.
Dept. of Surgery
Qian-Jin Zhang, Ph.D.
Dept. of Cellular Biology & Anatomy
Key Member
 |
Cherie-Ann
O. Nathan, M.D.
Professor, Vice-Chairman and Director
of Head and Neck Surgical
Oncology and Cancer Research
See
the Curriculum Vitae
Nathan Lab
The
translation initiation factor eIF4E is overexpressed in a variety of solid
tumors and in particular in all HNSCC (Nathan, Oncogne 1997). 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 (Nathan JCO, 1999). This was compared to p53 overexpression
in the margins and found to be a more sensitive marker for recurrence (Nathan,
Cancer Res 2000). 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 (Nathan, Oncogene 1997).
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.
Goals
1. To establish eIF4E antisense adenoviral vectors.
2. To demonstrate that this vector suppresses the growth of established tumors of the head and neck in cell culture and in animal models.
3. To then develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients.
