MOLECULAR EVENTS IN ORAL CANCER PROGRESSION/PREVENTION

  • Pearl, Dennis Keith (PI)
  • Weghorst, Christopher (PI)
  • Lang, James (PI)
  • Mallery, Susan (PI)
  • Milo, George (PI)
  • Stoner, Gary (PI)
  • Stoner, Gary (PI)

Project: Research project

Project Details

Description

The goals of the Oral Cancer Research Program (OCRPP) at The Ohio State
University are to: 1) enhance and facilitate investigations of those
interactions between human cells of the oral cavity and tobacco by-
products that lead to adverse biological responses; 2) coordinate
activities that will utilize the information obtained from these
interactions, at malignant oral lesions; and, 3) promote and develop
research that will determine the efficacy of control and intervention
strategies. Established investigators in the Oral Cancer Research Program
Project "Molecular Events in the Progress/Prevention of Oral Cancer" are
concentrating their efforts in five major areas of research (Research
Projects) to address this central theme. Research Project 1
(Carcinogen/Oxidant Synergism in Oral Cancer Initiation is focussing on
initiating events in oral cancer. They will determine the metabolic fate
of tobacco-associated carcinogens (TAC) in oral mucosal cells and how the
metabolism of these compounds may be modified by ethanol. Project 1 will
also explore the ability of oral mucosal cells to respond to
physiologically relevant concentrations of reactive oxygen species. The
genetic events leading to the establishment of premalignant and malignant
lesions will be studied by Research Projects 2 and 3. Research Project 2
(Role of G/1 Phase Regulatory Genes and Identification of Differentially
Expressed Novel Genes in Premalignant Oral Lesions) will evaluate those
genes more closely associated with aberrant cell proliferation. Research
Project 3 (Inactivation of the TGF-beta Receptor Complex in Oral Cancer
Development) will study the loss of control of cell cycle proliferation by
evaluating the effect of gene alterations (mutations, deletions,
methylation) on the TGF-beta receptor complex (i.e., protein binding,
kinase activity, and modification of specific downstream substrates).
Research Project 4 (Molecular Mechanisms in Conversion of Cells in Oral
Tissues from Normal to Premalignant and from Premalignant to Malignant)
will explore those conditions involved in the transformation of normal
cells into premalignant cells by TACs and the conversion of premalignant
oral dysplasias into squamous cell carcinomas. In concert with Research
Projects 2 and 3, the cells transformed in vitro by TAC, or concerted to
malignancy by TAC, will be examined to determine if the same changes occur
in cell cycle regulatory genes and the TGFbeta receptor complex as are
found in premalignant and malignant tissues form patients. The rationale
for the studies in Research Projects 1, 2, 3, and 4 is to provide
information on those premalignant to the malignant stage. This information
will be employed by Research Project 3 (Chemoprevention of Premalignant
and Malignant Oral Tumors) which will develop strategies for intervention
and preventive measures whereby the cytotoxic or genetic damage manifested
by tobacco-related products is inhibited or modified and progression of
dysplastic lesions to malignancy is prevented. This involves both natural
and synthetic chemicals that affect the activation and detoxification of
TAC and that interact with and modify the function of critical cellular
genes or gene products that are responsible for the generation and
maintenance of premalignant dysplasias and the conversion of these
dysplasia into malignant oral cancers. In summary, the major thrust of the
Program Project is to investigate the multiple genetic pathways in the
loss of regulatory control of cell proliferation, differentiation, and
apoptosis. With this information, we should be able to determine which
chemopreventative agents will best intervene in the early stages of the
cascade of events leading to oral cancer and by understanding the nature
of the molecular changes occurring in the early stages of disease, we can
develop strategies directed towards the modulation of those events that
are specifically involved in the process.
StatusFinished
Effective start/end date9/15/986/30/99

Funding

  • National Institute of Dental and Craniofacial Research

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