Abstract

Certain types of the human papillomavirus (HPV) are present in the tumor cells of many oral cancers. These viruses are tumorigenic when their transforming proteins are expressed, but we have shown that the cancer cells may lose many aspects of their malignant behavior when they are exposed to antisense nucleic acids of HPV. We will now optimize the use of antisense molecules, with the ultimate aim of developing therapeutic applications. We will screen different sites on the E6 and E7 genes of HPV-18 so as to find the most sensitive regions for inhibition by antisense oligonucleotides. We will measure the effects of hammerhead ribozymes to find if they are more effective than non-ribozyme molecules. We will find an effective method of delivering antisense constructs to oral epithelium, by comparing several virus vectors and promoters. The most effective virus vectors will then be tested in nude mice to find the feasibility of this method of gene therapy for human oral cancer. The project will be developed over a five-year period to the point where human clinical trials of therapy for malignant and premalignant lesions will be possible.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010842-03
Application #
2131735
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1994-02-01
Project End
1997-01-31
Budget Start
1995-02-01
Budget End
1996-01-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Upstate Medical University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210

  Publications

Gibson, S A; Pellenz, C; Hutchison, R E et al. (2000) Induction of apoptosis in oral cancer cells by an anti-bcl-2 ribozyme delivered by an adenovirus vector. Clin Cancer Res 6:213-22
Shillitoe, E J; Noonan, S (2000) Strength and specificity of different gene promoters in oral cancer cells. Oral Oncol 36:214-20
Shillitoe, E J; Gilchrist, E; Pellenz, C et al. (1999) Effects of herpes simplex virus on human oral cancer cells, and potential use of mutant viruses in therapy of oral cancer. Oral Oncol 35:326-32
Shillitoe, E J; Noonan, S; Hinkle, C C et al. (1998) Transduction of normal and malignant oral epithelium by particle bombardment. Cancer Gene Ther 5:176-82
Chen, Z; Storthz, K A; Shillitoe, E J (1997) Mutations in the long control region of human papillomavirus DNA in oral cancer cells, and their functional consequences. Cancer Res 57:1614-9
Gibson, S A; Shillitoe, E J (1997) Ribozymes. Their functions and strategies for their use. Mol Biotechnol 7:125-37
Chen, Z; Kamath, P; Zhang, S et al. (1996) Effects on tumor cells of ribozymes that cleave the RNA transcripts of human papillomavirus type 18. Cancer Gene Ther 3:18-23
Chen, Z; Kamath, P; Zhang, S et al. (1995) Effectiveness of three ribozymes for cleavage of an RNA transcript from human papillomavirus type 18. Cancer Gene Ther 2:263-71
Clayman, G L; Trapnell, B C; Mittereder, N et al. (1995) Transduction of normal and malignant oral epithelium by an adenovirus vector: the effect of dose and treatment time on transduction efficiency and tissue penetration. Cancer Gene Ther 2:105-11
Marini 3rd, F C; Cannon, J P; Belmont, J W et al. (1995) In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK. Hum Gene Ther 6:1215-23

Showing the most recent 10 out of 11 publications