title: Levels of proteolytic activities as intermediate marker endpoints in oral carcinogenesis.
abstract: It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142, USA.
authors.forename: H
authors.initials: H
authors.lastname: Manzone
authors.forename: P C
authors.initials: PC
authors.lastname: Billings
authors.forename: W N
authors.initials: WN
authors.lastname: Cummings
authors.forename: R
authors.initials: R
authors.lastname: Feldman
authors.forename: L C
authors.initials: LC
authors.lastname: Clark
authors.forename: C S
authors.initials: CS
authors.lastname: Odell
authors.forename: A M
authors.initials: AM
authors.lastname: Horan
authors.forename: J O
authors.initials: JO
authors.lastname: Atiba
authors.forename: F L
authors.initials: FL
authors.lastname: Meyskens
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002338:Carotenoids / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007971:Leukoplakia / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D010447:Peptide Hydrolases / Q000378:metabolism*; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects; D019207:beta Carotene
chemical_list: D000970:Antineoplastic Agents; D019207:beta Carotene; D002338:Carotenoids; D010447:Peptide Hydrolases