Other highlights in the September 1 JNCI

Retinoic acid therapy has been used as a treatment for neuroblastoma, but the drug can also make some neuroblastoma cells resistant to chemotherapy. Because fenretinide, a derivative of retinoic acid, targets a different molecular pathway--one that induces apoptosis, or programmed cell death--in neuroblastoma cells and is well tolerated, there has been interest in using fenretinide to treat neuroblastoma. In a study of fenretinide's activity within neuroblastoma cells, Chris P. F. Redfern, Ph.D., of the University of Newcastle upon Tyne in England, and colleagues characterize a novel pathway that mediates the fenretinide induction of apoptosis, and suggest that this pathway may be a target for future drug development. In addition, because fenretinide increased the level of a neuroblastoma cell marker--one that is targeted by immunotherapy--it may be able to work in conjunction with immunotherapy agents, the authors write.

Contact: University of Newcastle upon Tyne Press Office, 44-191-222-7850, press.office@ncl.ac.uk

Novel Compound Shows Activity Against Glucose-Deprived Tumors

Versipelostatin, a novel compound isolated from a microorganism, disrupts a stress-related pathway in glucose-deprived cancer cells and inhibits tumor growth in mice, according to a new study.

Tumors can become glucose- and oxygen-deprived when they lack blood vessels, which transport these molecules. Cells deprived of glucose accumulate unfolded proteins, but such cells survive this stress by turning on a special molecular pathway--the unfolded protein response--that protects cells from the harmful effects of unfolded proteins. Researchers have hypothesized that glucose-deprived tumor cells could be killed by disrupting this pathway.

Kazuo Shin-ya, Ph.D., of the University of Tokyo, and colleagues investigated the effect of versipelostatin on the unfolded protein response in human tumor cells and in a mouse tumor model. The drug inhibited expression of the molecular pathway in glucose-deprived tumor cells, and led to tumor cell death. In a mouse model, versipelostatin treatment inhibited tumor growth.

Contact: Kazuo Shin-ya, University of Tokyo, 81-3-5841-7840, kshin@iam.u-tokyo.ac.jp

New Assay Measures Effect of Immunotherapy in Cells of Melanoma Patients

Interferon alfa immunotherapy is used to treat patients with metastatic melanoma or renal cell carcinoma, but efforts to improve the treatment's efficacy are hampered by the lack of knowledge of its molecular targets. In a new study, William E. Carson III, M.D., of the Ohio State University in Columbus, and colleagues describe the use of a novel flow cytometric assay to measure activation by phosphorylation of the transcription factor STAT1 in response to immunotherapy. The researchers suggest that this new method may be able to help determine the optimal dose of interferon alfa for patients undergoing immunotherapy.

Contact: Michelle Gailiun, Ohio State University, 614-293-3737, gailiun-1@medctr.osu.edu

Scientists Outline Best Methods for Determining Health Benefits of Diet and Exercise

Changes in patterns of diet and exercise are needed to reverse the obesity epidemic and reduce the risk of chronic diseases, such as cancer, diabetes, and cardiovascular disease. However, there is little consensus among researchers about how to determine what interventions and changes would work the best. In a commentary on a 2003 workshop, Ross L. Prentice, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues outline research strategies and priorities for generating the needed information. They also provide specific research recommendations in four areas to provide physicians, government agencies, and educators with the information they need so they can provide the public with reliable advice on diet and exercise.

Contact: Kristen Woodward, Fred Hutchinson Media Relations, 206-667-5095, kwoodwar@fhcrc.org

Also in the September 1 JNCI: