Other highlights of the December 18 JNCI

December 17, 2002

Study Finds No Association Between Alcohol Consumption and Lung Cancer
Alcohol consumption does not appear to be associated with the risk of lung cancer, at least among light to moderate drinkers, according to a study appearing in the December 18 issue of the Journal of the National Cancer Institute.

Epidemiologic studies of the association between alcohol consumption and the risk of lung cancer have yielded mixed results. Luc Djoussé, M.D., D.Sc., of the Boston University School of Medicine, and his colleagues examined alcohol consumption by 4,265 participants of the Framingham Study, and 4,973 children of this cohort. Most of the participants were light to moderate drinkers. The authors used conditional logistic regression models to estimate the relative risk of lung cancer according to alcohol consumption. After adjusting for age, sex, amount of tobacco smoked, smoking status, and year of birth, the authors found that alcohol consumption was not statistically significantly associated with lung cancer in either the original cohort of the Framingham study or their children.

Body Surface Area Not Reliable for Determining Drug Dosage
Body surface area should not be used for determining appropriate starting doses of investigational anticancer drugs in future phase I studies, suggests a study in the December 18 issue of the Journal of the National Cancer Institute.

Sharyn D. Baker, Pharm.D., of the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, and colleagues retrospectively assessed the pharmacokinetics (i.e., drug clearance) as a function of body surface area of 33 investigational drugs tested in phase I trials from 1991 through 2001 in 1,650 adult cancer patients. They found that body surface area-based dosing was associated with a reduction in patient-to-patient variation in drug clearance for only five of the 33 agents. The authors suggest that alternate strategies should be evaluated for calculating doses of anticancer drugs.

Carbohydrate Binding Protein May Inhibit Tumor Growth
Carbohydrate-mediated recognition is important in many biologic processes, including tumor growth and metastasis. For example, binding of the carbohydrate binding protein galectin-3 to endothelial cells induces angiogenesis in vivo, and galectin-3 levels are directly related to the stage of progression of some tumors. In a study in the December 18 Journal of the National Cancer Institute, Pratima Nangia-Makker, Ph.D., and Avraham Raz, Ph.D., of Wayne State University in Detroit, Mich., and their colleagues further investigated the in vivo role of galectin-3 by feeding nude mice with modified citrus pectin (MCP), a nondigestible polysaccharide fiber that specifically inhibits galectin-3, and then injecting the mice with human cancer cells. They found that tumor growth, angiogenesis, and spontaneous metastasis were statistically significantly lower in MCP-fed mice than in control mice. MCP also blocked a number of galectin-3-mediated functions in vitro, including capillary tube formation, galectin-3-induced chemotactic migration, and galectin-3-mediated adhesion. The authors note that their results highlight the potential importance of dietary carbohydrate compounds as agents for cancer prevention and/or treatment.

RNA Silencing of Polo-Like Kinase May be Effective Against Human Cancer Cells
The polo-like kinases (PLKs) are key regulators of mitotic progression in mammalian cells, and the activity of PLK1 is elevated in cancer cells. To investigate the role of PLK1 in malignant cell proliferation, Birgit Spänkuch-Schmitt and Klaus Strebhardt, of J. W. Goethe-University in Frankfurt, Germany, and colleagues used RNA interference to inhibit PLK1 expression in several human cancer cell lines. Cancer cells transfected with small interfering RNAs (siRNAs) targeted to the human PLK1 gene grew at a reduced rate and showed increased cell death. Cell structure analysis revealed that the centrosomes of siRNA-transfected SW-480 colon cancer cells had lost the ability to nucleate microtubules. In contrast to cancer cells, human mammary epithelial cells took up siRNAs poorly and did not display growth inhibition. The authors note that siRNAs targeted to PLK1 have high specificity and potent inhibitory effects at low concentrations, both of which are important for potential pharmacologic agents. Their findings are reported in the December 18 issue of the Journal of the National Cancer Institute.
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Journal of the National Cancer Institute

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