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Other highlights in the May 5 JNCI

Journal of the National Cancer Institute

Selenium May Slow Prostate Cancer Tumor Progression

Higher plasma selenium levels are associated with a decreased risk of advanced prostate cancer, according to a new study. This may indicate that higher selenium levels could slow prostate cancer tumor progression.

Haojie Li, M.D., Ph.D., of Brigham and Women's Hospital and Harvard Medical School, and colleagues analyzed plasma samples, obtained in 1982, from a subset of healthy men enrolled in the Physicians' Health Study, some of whom were diagnosed with prostate cancer during the subsequent 13 years. The researchers found that higher plasma selenium levels were associated with a decreased risk of subsequent advanced prostate cancer. Among men who had increased prostate-specific antigen (PSA) levels in 1982, the researchers also found an association between higher selenium levels and a reduced risk of all prostate cancer.

In an editorial, Scott M. Lippman, M.D., of The University of Texas M. D. Anderson Cancer Center in Houston, and colleagues give an overview of research on selenium's effects on prostate cancer. This new study, they write, continues "to support the initial impression of this agent's tremendous potential as a prostate cancer preventative agent."

Contact: Amy Dayton, Brigham and Women's Hospital, 617-534-1603,

Researchers Identify Possible New Target for Inhibiting Tumor Angiogenesis

Inactivating the mRNA for c-Jun, a transcription factor, inhibits angiogenesis--the development of new blood vessels--and tumor growth in rodent models, according to a new study.

Levon M. Khachigian, Ph.D., of The University of New South Wales in Sydney, Australia, and colleagues suppressed expression of c-Jun in microvascular endothelial cells (the cells that line blood vessels) by transfecting them with a DNA enzyme (DNAzyme) targeting c-Jun mRNA, and studied the properties of the transfected cells in vitro and in rodent models of tumorigenesis and angiogenesis. The DNAzyme-transfected endothelial cells expressed less c-Jun protein than mock-transfected cells. Transfection with the DNAzyme blocked endothelial cell proliferation and migration in vitro, inhibited angiogenesis in rat corneas, and inhibited solid melanoma growth in mice.

In an editorial that accompanies the article, Judah Folkman, M.D., of Children's Hospital in Boston, writes, "DNAzymes targeting c-Jun could act as both direct and indirect inhibitors of angiogenesis."

Contact: Levon M. Khachigian, Centre for Vascular Research, The University of New South Wales, 61-29-385-2537,

Examining the Potential Conflicts of Interest of Clinical Trial Participants

Research subjects in early clinical trials should avoid trading stock in the company that owns the drug being tested because these conflicts of interest could interfere with the trials, according to a commentary by a group of oncologists and bioethicists.

Research subjects often have access to unpublished information when they enroll in a clinical trial and have been known to sometimes trade stock based on this information. In their commentary, Paul R. Helft, M.D., of the Indiana University School of Medicine, and colleagues examine the scientific, ethical, and legal concerns raised by the possibility of this type of conflict of interest. These conflicts may interfere with a participant's honest reporting of a treatment's toxic effects and, if known by their physician, could negatively affect the patient-physician relationship and the process of informed consent. In addition, subjects who use information from trials in which they participate to make decisions on the stock market could potentially face legal consequences for insider trading.

The authors suggest studying the extent of these conflicts of interest and, if they are discovered to be widespread, instituting measures to screen clinical trial participants and require them to cease trading the sponsoring company's stock until the trial's results become public.

Contact: Mary Hardin, Public and Media Relations, Indiana University School of Medicine, 317-274-7722,

Glucocorticoid Prescriptions Associated with Risk of Skin Cancers, Non-Hodgkin's Lymphoma

Glucocorticoid treatment may be associated with an increased risk of developing skin cancers and non-Hodgkin's lymphoma, according to a new study. Glucocorticoids are a group of immunosuppressive drugs, such as prednisone, that are used to treat acute and chronic inflammatory diseases.

Henrik Toft Sørensen, M.D., Ph.D., of Aarhus University Hospital in Aarhus, Denmark, and colleagues identified 59,043 individuals from the North Jutland Prescription Database--a computerized pharmacy database of prescriptions in Denmark--who had received a glucocorticoid prescription between 1989 and 1996. Data for these individuals were linked to the Danish Cancer Registry, which collects information on all people diagnosed with cancer. The number of actual cases of non-Hodgkin's lymphomas and skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, among people receiving glucocorticoid prescriptions were compared with the expected number. There were more cases of all these cancers than expected, particularly among people who had received 15 or more glucocorticoid prescriptions, indicating that use of glucocorticoids may be a shared risk factor for certain cancers and lymphomas.

Contact: Henrik Toft Sørensen, Aarhus University Hospital, 45-89-42-6077,

Scientists Develop Method That May Detect Breast Cancer Metastasis

A new method that allows researchers to visualize sentinel lymph node drainage in mice may be able to detect lymph node metastases from breast cancer.

Lymph node metastases are an indicator of prognosis in breast cancer patients and a major criterion in determining the need for adjuvant chemotherapy. Although a biopsy can detect these metastases, there is a need for an accurate and noninvasive method of detection.

Hisataka Kobayashi, M.D., Ph.D., of the National Cancer Institute, and colleagues developed a method in which nano-size molecules were used as contrast agents during magnetic resonance imaging to detect sentinel lymph node drainage in normal mice and mouse models of breast cancer. Using this method, regions of sentinel lymph nodes that contained metastatic tumors appeared as black spots while regions without tumors and lymph nodes in normal mice appeared white. This new imaging method, the authors conclude, has the potential to be used to detect sentinel lymph node metastases in human breast cancer patients.

Contact: NCI Press Office, 301-496-6641

Scientists Highlight Apoptosis as a Target for Cancer Chemoprevention

A growing number of chemopreventive agents, including some retinoids and nonsteroidal anti-inflammatory drugs, have been shown to stimulate programmed cell death--apoptosis--in precancerous and malignant cells. Reuben Lotan, Ph.D., of The University of Texas M. D. Anderson Cancer Center in Houston, and colleagues review recent studies of several chemopreventive agents and construct a paradigm for apoptosis as a target for cancer chemoprevention.

Contact: Laura Sussman, Communications Office, M.D. Anderson Cancer Center, 713-745-2457,

Also in the May 5 JNCI:
Small Gene Changes in Some Leukemia Patients May Explain Varying Responses to Chemotherapy:


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