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Other highlights in the December 7 JNCI

Journal of the National Cancer Institute

Chronic Stress Associated With Increased Risk of Skin Cancer in Animal Study

A new study in mice has found that chronic stress may increase susceptibility to a type of skin cancer that is induced by ultraviolet (UV) radiation by suppressing T cells and certain molecules that support immune function.

Both chronic stress and exposure to UV radiation suppress the immune system, but the mechanism by which suppression occurs is not fully understood. A group of scientists at Ohio State University in Columbus, led by Firdaus S. Dhabhar, Ph.D., wanted to find out if and how UV radiation and chronic stress act together to increase susceptibility to disease. They studied immune response and tumor formation in mice exposed to either UV radiation or to UV radiation and chronic stress.

In mice that were exposed to both UV radiation and chronic stress, tumors formed more quickly than in mice that were only exposed to UV radiation. Researchers observed suppression of T-cell function and molecules called type 1 cytokines, both of which work to enhance immune functioning. The authors write, "Our results show that a moderate chronic stressor, one that does not have overall health-aversive effects (no change in body and organ weights), can substantially increase susceptibility to skin cancer."

Contact: Firdaus S. Dhabhar, Ohio State University, 614-209-0602,

Dairy Product and Calcium Intake May Be Associated with Increased Risk of Prostate Cancer

Although the most recent U.S. government guidelines recommend that Americans increase their dairy product intake, several studies have reported that high intake of dairy products and calcium is associated with an increased risk of prostate cancer.

In a meta-analysis, Xiang Gao, Ph.D., and Katherine L. Tucker, Ph.D., at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, and Michael P. LaValley, Ph.D., from Boston University School of Public Health, reviewed data from 12 publications, published from 1966 to May 2005, which reported on the association between calcium or dairy product intake and the risk of prostate cancer. They found that men with the highest intakes of calcium and dairy products had an increased risk of prostate cancer compared with men with the lowest intakes. However, the researchers note that the increased risk appears to be small.

Contact: Siobhan Gallagher, Health Sciences Public Relations, Tufts University, 617-636-6586

Smad7 Expression Inhibits Metastasis in Mouse Mammary Cancer Cells

A new study suggests that a protein called Smad7 can inhibit tumor spread, or metastasis, in mouse mammary cells during advanced stages of cancer by inhibiting the signaling molecule TGF-beta which promotes cancer progression.

Increased levels of TGF-beta have been associated with tumor progression and spread. However, TGF-beta and related proteins cannot send signals without the help of Smad proteins, several of which have been known to inhibit TGF-beta signaling.

Haruhito Azuma, M.D., Kohei Miyazono, M.D., and colleagues at the Osaka Medical College in Japan tested the effect of three inhibitors of TGF-beta superfamily signaling - Smad6, Smad7, and c-Ski - on mammary tumors in mice. Mice treated with Smad7 and c-Ski survived for longer periods of time and showed decreased metastasis than untreated mice. They found Smad7 expression was associated with an alteration in levels of molecules found in adherens junctions, structures involved in the adhesive properties of cells, such as E- and N-cadherin. The researchers suggest that Smad7 may be a novel strategy to investigate as a treatment for advanced metastatic cancers.

In an editorial, Isaiah J. Fidler, D.V.M., Ph.D., at the University of Texas M. D. Anderson Cancer Center in Houston, remains skeptical that Smad7 could be used to treat advanced metastatic cancer in patients. Fidler cites the authors' evidence that Smad7 does not eliminate existing metastatic lesions, although Smad7 inhibits development of new metastases. "Patients with advanced-stage disease already have well-established metastases for which the inhibition of tumor cell motility is unlikely to produce therapeutic results," he writes.

Contacts: Article: Kohei Miyazono, Osaka Medical College, 81-3-5841-3356, Editorial: Stephanie Dedeau, Communications Office, M.D. Anderson Cancer Center, 713-792-0655,

Plant Compound Toxic to Cancer Cells

A study conducted by Peng Huang, M.D., Ph.D., at the M. D. Anderson Cancer Center in Houston, and colleagues found that a compound in the bulbs of the Ornithogalum saudersiae, or the Ivory coast lily, was effective in killing human leukemia and pancreatic cancer cells in laboratory tests.

The compound, called OSW-1, was more toxic to cancer cells than non-cancer cells. In leukemia and pancreatic cells, OSW-1 targeted cell organelles called mitochondria, and induced an abnormal increase of cytosolic calcium, leading to apoptotic death of the cancer cells. The researchers think that the compound displays potent anticancer activity, and they suggest that research move toward animal toxicity studies before clinical testing.

Contact: Laura Sussman, Communications Office, M.D. Anderson Cancer Center, 713-792-0655,

Also in the December 7 JNCI:


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