Gary D Stoner
Department of Medicine, Hematology and Oncology
Medical College of Wisconsin
Dr. Gary Stoner is Professor of Medicine at the Medical College of Wisconsin (MCW) Division of Hematology and Oncology, specializing in the fields of chemical carcinogenesis and cancer chemoprevention. He serves as Director of the Molecular Carcinogenesis and Chemoprevention Program in the newly developing Cancer Center.Dr. Stoner received his PhD in microbiology from the University of Michigan in 1970 and became involved in cancer research as a post-doctoral fellow and research scientist at the University of California-San Diego (UCSD). While at UCSD, his research was focused on the development of a mouse model of lung cancer for the identification of environmental carcinogens and for mechanistic studies of lung carcinogenesis. He then joined the Laboratory of Human Carcinogenesis at the National Cancer Institute where he conducted research on the metabolism of tobacco carcinogens in human lung tissues and developed human lung cell culture systems for investigations of carcinogen/oncogene-induced cell transformation. He became involved in chemoprevention research in the early 1980’s while at the Medical College of Ohio, initially investigating the chemopreventive potential of naturally-occurring ellagitannins and isothiocyanates in the rodent lung and esophagus. As an extension of research with ellagic acid, Dr. Stoner’s laboratory developed a “food-based” approach to the prevention of esophagus and colon cancers in rodents and in humans using freeze-dried black raspberries. His research is documented in more than 350 peer-reviewed publications and book chapters, and he has edited several books.
We examined the ability of freeze-dried berries to prevent G.I. tract cancers in animals and humans. Most studies used black raspberries (BRBs), due to their high antioxidant potential and high content of anthocyanins and fi ber. In rodent studies, the consumption of BRB powder, at 2.5, 5 and 10% of a synthetic diet, resulted in a 40-70% inhibition of carcinogeninduced cancer in the rat esophagus and colon, and the spontaneous development of intestinal tumors in mice. Mechanistically, BRBs inhibit proliferation, infl ammation and angiogenesis and stimulate apoptosis and diff erentiation, and protectively modulate genes in multiple signaling pathways. Th e most active inhibitory constituents in BRBs are the anthocyanins. A Phase I trial showed that BRBs are well tolerated in humans at oral doses that elicit chemopreventive eff ects in rodents. Th e oral administration of BRB powder (45g/day) to 20 Barrett’s esophagus patients for 6 months led to reductions in oxidative stress, but minimal eff ects on the lesion. Oral administration of strawberry powder (60g/day) to 37 Chinese patients with esophageal dysplasia led to histologic regression of ~80% of mildly dysplastic lesions and reduced levels of iNOS, COX-2, and phospho-NF-κB-p65 proteins. Treatment of 20 colorectal cancer patients with BRB powder for an average of 3 weeks led to reduced cell proliferation and demethylation of suppressor genes in the Wnt signaling pathway. Treatment of patients with familial adenomatous polyposis with rectal BRB suppositories caused a 36% regression of rectal polyps. Th ese trials indicate that berries have signifi cant promise for chemoprevention of esophageal and colon cancer in humans.