- Biology of multistage carcinogenesis using in vitro models of normal, premalignant and malignant oral epithelial cells.
- Development of new chemopreventive strategies/agents for oral cancer.
- Dysregulated mitosis: a new chemopreventive mechanism for curcumin.
- Development of an in vitro oral multistage carcinogenesis model to analyze tobacco-induced mutations.
- Biology of the premalignant state.
Multistage Carcinogenesis, Premalignancy and Oral Cancer
My laboratory is interested in the biology of oral cancer. We have established an in vitro human multistage carcinogenesis model for oral cancer, consisting of primary cultures of normal oral epithelial cells, cell lines developed from dysplastic leukoplakia (considered premalignant) and oral squamous carcinoma cell lines. The biological basis of precancer is ill understood and we are examining the influence of the microenvironment on cell-cell interactions (normal? progressed cells) as a model for premalignant lesions. The microenvironment encompases the spatial organization of cells and includes influences of extracellular matrix material on which epithelial cells rest as well as information that is received from the stromal compartment. The microenvironment will influence cell-cell interactions and tissue homeostasis. In addition to studying the biology of the premalignant state, cell lines from dysplastic leukoplakia are relevant for examining the concept of chemoprevention. As a therapeutic modality, chemoprevention has shown efficacy with precancereous oral tissues. We are using our in vitro models to examine specific preventive agents with respect to efficacy and mechanisms of action.
Sacks, P.G., Parnes, S.M., Price, J.C., Risemberg, H., Goldstein, J.C., Parsons, D.F. In vitro control of differentiation by calcium in explants of human and murine epithelial tissues. In Vitro 21 (1985):99-107.
Sacks, P.G., Parnes, S.M., Gallick, G.E., Mansouri, .Z, Lichtne,r R., Satya-Prakash, K.L., Pathak, S., Parsons, D.F. Establishment and characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck. Cancer Research, 48 (1988):2858-2866.
Parthasarathy, R., Sacks, P.G., Harris, D., Brock, H., Mehta, K. Interaction of liposome-associated all-trans-retinoic acid with squamous carcinoma cells. Cancer Chemotherapy and Pharmacology 34 (1994):527-534.
Sturgis, E., Sacks, P.G., Masui, H., Mendelsohn, J., Schantz, P.G. The effects of anti-epidermal growth factor receptor antibody 528 on the proliferation and differentiation of head and neck cancer. Otolaryngology Head & Neck Surgery 111 (1994):633-643.
Sacks, P.G., Harris, D., Chou, T-C. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy with chemotherapeutic agents. International Journal of Cancer, 61 (1995):409-415.
Sacks, P.G. Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck. Cancer and Metastasis Reviews 15 (1996):27-51.
Sacks, P.G., Savage, H.E., Levine, J., Kolli, V.R., Alfano, R.R., Schantz, S.P. Native cellular fluorescence identifies terminal squamous differentiation of normal oral epithelial cells in culture: a potential chemopreventive biomarker. Cancer Letters 104 (1996):171-181.
Xu, L., Schantz, S.P., Edelstein, D., Sacks, P.G. A simplified method fot the routine culture of normal oral epithelial (NOE) cells from upper aerodigestive mucosa. Methods in Cell Science 189 (1996):1-9.
Sacks, P.G., Amos, B., Lotan, R. Enhancement of glycosylation of cellular glycoconjugates in the squamous cell line MDA886Ln by b-all-trans retinoic acid. Glycoconjugate Journal 13 (1996):791-796.
Kelley, D.J., Mestre, J.R., Subbaramaiah, K., Sacks, P.G., Schantz, S.P., Tanabe, T., Inoue, H., Ramonetti, J.T., Danenberg, A.J. Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells. Carcinogenesis, 18 (1997): 795-799.
Zhang, J.C., Savage, H.E., Sacks, P.G., Delohery, T., Alfano, R.R., Latz, A., Schantz, S.P. Innate cellular fluorescence reflects alterations in cellular proliferation. Lasers in Surgury and Medicine 20 (1997):319-331.
Spingarn, A., Sacks, P.G., Kelley, D., Dannenberg, A.J., Schantz, S.P. Synergistic effects of 13-cis retinoic acid and arachidonic acid cascade inhibitors on growth of head and neck squamous cell carcinoma in vitro. Otolaryngol-Head and Neck Surgery 118 (1998):159-164.
Khafif, A., Schantz, S.P, Chou, T-C., Edelstein, D., Sacks, P.G. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells. Carcinogenesis, 19 (1998):419-424.
Khafif, A., Schantz, S.P., Al-Rawi, M. Edelstein, D., Sacks, P.G. Green tea regulates cell cycle progression in oral leukoplakia. Head & Neck 20 (1998):528-534.
Ganesan S. Sacks PG. Yang Y. Katz A. Al-Rawi M. Savage HE. Schantz SP. Alfano RR. Native fluorescence spectroscopy of normal and malignant epithelial cells. Cancer Biochemistry Biophysics 16 (1998):365-73.
Carew JF. Federoff H. Halterman M. Kraus DH. Savage H. Sacks PG. Schantz SP. Shah JP. Fong Y. Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector. American Journal of Surgery 176 (1998):404-8.
Gillenwater A. Xu XC. Estrov Y. Sacks PG. Lotan D. Lotan R. Modulation of galectin-1 content in human head and neck squamous carcinoma cells by sodium butyrate. International Journal of Cancer. 75 (1998):217-24.
Chan G. Boyle JO. Yang EK. Zhang F. Sacks PG. Shah JP. Edelstein D. Soslow RA. Koki AT. Woerner BM. Masferrer JL. Dannenberg AJ. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Research 59 (1999):991-4.
Mestre JR. Chan G. Zhang F. Yang EK. Sacks PG. Boyle JO. Shah JP. Edelstein D. Subbaramaiah K. Dannenberg AJ. Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer. Ann New York Academy of Science 889 (1999):62-71.
Michaluart P. Masferrer JL. Carothers AM. Subbaramaiah K. Zweifel BS. Koboldt C. Mestre JR. Grunberger D. Sacks PG. Tanabe T. Dannenberg AJ. Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Research 59 (1999):2347-52.
Singh B. Gogineni SK. Sacks PG. Shaha AR. Shah JP. Stoffel A. Rao PH. Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification. Cancer Research 61 (2001):4506-4513.
Abraham MT. Kuriakose A. Sacks PG. Yee H. Chiriboga L. Bearer EL. Delacure MD. Motility-related proteins as markers for head and neck squamous cell carcinoma. The Laryngoscope 111 (2001):1285-1289.
