A phase IIb study of anethole dithiolethione (ADT) in smokers with bronchial dysplasia (pre-malignant lesions in the lung) suggests that the compound is an effective chemopreventive strategy for lung cancer control. These findings appear in the July 3 issue of the Journal of the National Cancer Institute.
ADT is one of two organosulfur compounds that are being studied for their ability to stimulate the production of enzymes that detoxify carcinogens. ADT has been approved in Canada and Europe for the treatment of drug- and radiation-induced dryness of the mouth and other conditions. To examine the effectiveness of ADT as a chemopreventive agent in lung cancer, Stephen Lam, M.D., of the British Columbia Cancer Agency and the University of British Columbia, and his colleagues randomly assigned 112 current and former smokers with bronchial dysplasia to receive either ADT or a placebo for 6 months.
Compared with patients who received placebo, those who received ADT had a lower rate of progression by two or more grades of preexisting dysplastic lesions and a reduction in the appearance of new lesions. Side effects of ADT were minor and included gastrointestinal symptoms that subsided after dose reduction or completion of ADT treatment.
Vitamin B12 May be Effective Carrier of Anticancer Drug:
Vitamin B12,
an essential micronutrient, is required by tumors in increased concentrations compared with normal tissue. Joseph A. Bauer, Ph.D., and Daniel J. Lindler, M.D., Ph.D., of the Cleveland Clinic Foundation, and their colleagues examined whether a vitamin B12 analogue could be used as a carrier molecule to direct a chemotherapy drug to tumor cells.
The authors attached nitric oxide, which is toxic when internalized by cells, to vitamin B12. When mice bearing human tumors were treated with this compound, the tumors regressed. However, when the mice were treated with the nitric oxide-vitamin B12 analogue plus interferon β, which increases expression of the receptor that takes vitamin B12 into cells, the tumors were eradicated. The authors suggest that the vitamin B12 analogue inhibited tumor growth by inducing apoptosis, or cell death. The findings appear in the July 3 issue of the Journal of the National Cancer Institute.
Aminopeptidase Helps Leukemia Cells Resist Death:
One type of leukemia cell, called NB4, expresses high levels of a cell-surface protein called aminopeptidase and, unlike other types of leukemia cells, does not appear to undergo cell death induced by endothelial cell-derived interleukin 8. To find out why, Kiyohiko Hatake, Ph.D., of the Japanese Foundation for Cancer Research in Tokyo, and his colleagues examined aminopeptidase activity in several leukemia cell lines. When the authors increased levels of aminopeptidase, they found that the leukemia cells resisted apoptosis induced by IL-8. However, the addition of bestatin, an inhibitor of aminopeptidase, restored the cells' ability to undergo apoptosis. The authors conclude that bestatin may be useful for treating patients with leukemia.
Mechanism Suggested For Insulin and Colon Cancer:
Studies have suggested that certain dietary and associated factors may increase the risk of colorectal cancer by changing blood insulin concentrations, but the mechanism has been unclear. In the July 3 issue of the Journal of the National Cancer Institute, Manjinder S. Sandhu, M.Sc., of the University of Cambridge, and colleagues review data on the biologic interactions among insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor proteins (IGFBPs). They suggest that elevated insulin levels may block the production of one or more IGFBPs, leading to an increase in IGF-I, a molecule that can promote tumor cell growth and inhibit tumor cell death.
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Journal
JNCI Journal of the National Cancer Institute