Journal Article

Etiology and chemoprevention of esophageal squamous cell carcinoma

Gary D. Stoner and Ashok Gupta

in Carcinogenesis

Volume 22, issue 11, pages 1737-1746
Published in print November 2001 | ISSN: 0143-3334
Published online November 2001 | e-ISSN: 1460-2180 | DOI:
Etiology and chemoprevention of esophageal squamous cell carcinoma

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Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Current modalities of therapy for this disease offer poor survival and cure rates. Although a number of approaches could be undertaken to reduce the occurrence of esophageal SCC, including changes in lifestyle and improved nutrition, such approaches are not easily implemented. Chemoprevention offers a viable alternative that is likely to be effective against this disease. Clinical investigations in areas of high incidence of esophageal SCC have shown that primary chemoprevention of this disease is feasible, if potent inhibitors are identified. Studies in the Fischer 344 rat model of nitrosamine-induced tumorigenesis have proven valuable in understanding the biology of esophageal SCCs and help identify surrogate end-point biomarkers and putative agents that can be useful in human chemoprevention studies. Several compounds that inhibit tumor initiation by suspected human esophageal carcinogens have been identified using this model. These include diallyl sulfide, isothiocyanates and several polyphenolic compounds. Novel biomarkers, including nuclear/nucleolar morphometry using computer-assisted image analysis of preneoplastic lesions, have been developed to measure efficacy of chemopreventive agents against esophageal SCC. The identification of single agents that inhibit the progression of dysplastic lesions, however, has proven difficult. Results from a food-based approach suggest that the use of freeze-dried berry preparations can affect both initiation and promotion/progression of esophageal SCC in an animal model. These observations provide valuable information for future studies on chemoprevention of cancers of the esophagus in a clinical setting. Given the complex etiology of esophageal SCC, it is felt that the most effective chemoprevention strategies would include agents that reduce mutational events associated with carcinogen exposure in combination with agents that inhibit the progression of intraepithelial dysplasia to invasive cancer.

Keywords: ATB, antitumor-B; BITC, benzyl isothiocyanate; BRB, freeze-dried black raspberries; CAQITA computer-assisted quantitative image tile analysis; CYP2E1, cytochrome P450 2E1; EA, ellagic acid; 4-ECPR; 4-ethoxycarbophenylretinamide; EGCG, (–)-epigallocatechin 3-gallate; 4-HPR, N-(4-hydroxyphenyl)retinamide; HPV, human papilloma virus; MTG, mean tile grade; NMBA, N-nitrosomethylbenzylamine; NNN, N-nitrosonornicotine; PBITC, phenylbutyl isothiocyanate; PCNA proliferating cell nuclear antigen; PEITC, phenethyl isothiocyanate; PHITC, phenylhexyl isothiocyanate; PPITC, phenylpropyl isothiocyanate; SCC, squamous cell carcinoma; STRW, lyophilized strawberry preparation; %TG>4SD, percent tile grade >4 SD; TOC, tylosis esophageal cancer.

Journal Article.  8586 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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