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Molecular predictors of oral cancer development

Institution: University of California, San Francisco
Investigator(s): Richard Charles Jordan, D.D.S., Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0141 Award: $419,000
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Oral cancer is the 6th most common form of cancer in the world. The vast majority are caused by tobacco. Despite advances in its management, the 5-year survival rate has remained disappointingly low, at about 40%, for the past several decades. This indicates the need for new strategies to improve outcome. One such strategy is to better understand the earliest forms of oral cancer, in the precancerous stage, with the long-term aim of preventing progression to fully developed disease. Oral dysplasia (precancer) is the single most important risk factor for oral cancer; however, only about 20% of all patients with precancer will ever progress to malignancy. Presently, for the individual patient with precancer, there are no reliable markers that indicate which lesion will progress to oral cancer. Therefore, it is important to identify new markers, present in precancerous lesions, which may predict oral cancer development.

This study will study the development of oral cancer by examining a large group of patients with oral precancer who have been followed in a specialized clinic for several years. By doing this we now know which patient with oral precancer went on to oral cancer and who did not. We will study the expression of new molecules (markers), that we discovered using gene hunting technology (gene chips), in these tissues to determine which of these markers can distinguish patients that go on to oral cancer from those that do not. To do this we will use a new technique called TaqMan PCR that can be applied to paraffin embedded tissue biopsies that the patients had several years earlier.

This work is innovative because it takes advantage of state-of-the-art technical advances to assess markers in one of the largest groups of patients with oral precancers and cancers with several years of follow-up. This is exceptionally difficult material to collect and thus provides a unique opportunity to identify molecular markers that may help predict oral cancer. We expect that our approach will identify important markers that are altered during the progression of oral precancer to oral cancer. These results will be significant because they are expected to provide new markers for screening and for preventive measures.
Publications

Quantitative analysis of cathepsin L mRNA and protein expression during oral cancer progresion.
Periodical: Oral Oncology European Journal Cancer B Index Medicus:
Authors: Macabeo-Ong, Shiboski CH, Silverman S, Ginzinger DG, Dekker N, Wong DTW, Jordan RCK ART
Yr: 2003 Vol: 39 Nbr: Abs: Pg: 638 - 647

Effect of formalin fixation time on quantitative RT-PCR expression analysis.
Periodical: Modern Pathology Index Medicus:
Authors: Macabeo-Ong M, Ginzinger DG, Dekker N, McMillan A, Regezi JA, Wong DTW, Jordan RCK ART
Yr: 2002 Vol: 15 Nbr: 9 Abs: Pg: 979-987

Proliferation and invasion factors in HIV-associated dysplastic and non-dysplastic oral warts, and oral squamous cell carcinoma: an immunohistochemical and RT-PCR evaluation.
Periodical: Oral Surgery Oral Medicine Oral Pathology Index Medicus:
Authors: Regezi JA, Dekker N, Ramos DM, Li X, Macabeo-Ong M, Jordan RCK ART
Yr: 2002 Vol: 94 Nbr: Abs: Pg: 724-731

Assessment of p63 expression in oral squamous cell carcinomas and dysplasis.
Periodical: Oral Surgery Oral Medicine Oral Pathology Index Medicus:
Authors: Bortoluzzi MC, Yurgel LS, Dekker NP, Jordan Rick, Regezi JA ART
Yr: 2004 Vol: 98 Nbr: Abs: Pg: 698 - 704

Overexpression of matrix metalloproteinases-1 and 9 mRNA are associated with progression of oral dysplasia to cancer.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Jordan, R, Macabeo-Ong M, Shiboski CH, Ginzinger DG, Wong DTW, Schmidt BL ART
Yr: 2004 Vol: 10 Nbr: Abs: Pg: 6460 - 6465

Increased nitric oxide levels and iNOS overexpression in oral squamous cell carcinoma.
Periodical: Oral Oncology European Journal Cancer B Index Medicus:
Authors: Connelly ST, Macabeo-Ong M, Jordan R, Schmidt BL ART
Yr: 2005 Vol: 41 Nbr: 3 Abs: Pg: 261 - 267