A new study shows how testing for an immune response to the prostate cancer biomarker alpha-methylacyl-CoA racemase (AMACR) could be used to help detect prostate cancer in men with intermediate prostate-specific antigen (PSA) levels.
Although PSA screening for prostate cancer has become widespread in the United States, the test has a high rate of false positives because benign diseases, such as prostate enlargement, can increase PSA levels. AMACR expression has been shown to be increased in prostate cancers, but AMACR levels in blood are too low to be detected.
To determine whether an immune response to AMACR could be used instead as a biomarker for prostate cancer, Arul M. Chinnaiyan, M.D., Ph.D., of the University of Michigan Medical School in Ann Arbor, and colleagues used protein microarrays to look for an immune response to AMACR in patients with prostate cancer and in healthy control subjects. The patients with prostate cancer all had a higher immune response to AMACR compared with the control subjects. The authors suggest that the test may be useful in detecting prostate cancer and reducing the number of biopsies done, particularly in men who have intermediate PSA levels.
In an editorial, H. Ballentine Carter, M.D., and William B. Isaacs, Ph.D., of Johns Hopkins School of Medicine in Baltimore, write, "The value of the present study may be the proof of principle that screening for an immune response to cancer-specific antigens by using protein microarrays could lead to improved biomarkers of disease."
Contact: Sally Pobojewski, Senior Science Writer, University of Michigan Medical School, 734-764-2220, pobo@umich.edu
More Effective Method of PLK1 Gene Silencing Inhibits Tumor Growth
The therapeutic use of gene silencing through RNA interference with small interfering RNAs is limited because its effects last for at most 1 week. A new strategy that instead uses short hairpin RNAs (shRNAs) to suppress expression of the gene for a key cell cycle regulator in a mouse model appears to silence the gene for a longer time.
Birgit Spänkuch, J. W. Goethe-University in Frankfurt, Germany, and colleagues used a xenograft mouse model to investigate whether an RNA interference strategy that used shRNAs could suppress expression of polo-like kinase 1 (PLK1), a key cell cycle regulator that is overexpressed in some human tumors, and inhibit tumor growth in vivo.
Levels of PLK1 mRNA and protein were lower in cancer cells that had been transfected with shRNA plasmids designed to interfere with PLK1 compared with cells transfected with control plasmids. In addition, tumor growth was reduced in mice treated with the shRNA plasmids compared with control mice.
Contact: Klaus Strebhardt, J.W. Goethe-University, strebhardt@em.uni-frankfurt.de
New AJCC Breast Cancer Staging System Influences False-Negative Rates
The latest edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer redefined how metastases in the axillary lymph nodes are classified. David R. McCready, M.D., M.Sc., of the University of Toronto, and colleagues explored how the revision affected sentinel lymph node positivity, the false-negative rate, and the overall accuracy of the sentinel lymph node biopsy in a cohort of 205 breast cancer patients undergoing breast cancer surgery that included sentinel lymph node biopsy and removal of the axillary lymph nodes.
Based on their results, the authors conclude that "this study supports the concept that the sentinel lymph node should be carefully and intensely examined for this procedure to be most accurate."
Contact: Vince Rice, Public Affairs, Princess Margaret Hospital, 416-946-2000 x5771, vince.rice@uhn.on.ca
Study Finds Possible New Mechanism for Estrogen's Promotion of Breast Cancer
Most studies of estrogen's ability to promote breast tumor growth have focused on mechanisms that increase tumor proliferation, but estrogen may also play a role in the regulation of angiogenesis, or blood vessel formation. Hynda K. Kleinman, Ph.D., of the National Institute of Dental and Craniofacial Research in Bethesda, Md., and colleagues show how estrogen may act as an angiogenic switch and allow progression of breast carcinoma.
Contact: Susan Johnson, National Institute of Dental and Craniofacial Research, National Institutes of Health, 301-496-4260, johnsonS@od31.nidr.nih.gov
Zoledronic Acid Treatment Benefits Men with Metastatic Prostate Cancer
A majority of patients with advanced prostate cancer experience metastatic bone disease, including severe bone pain and pathologic fractures. In a follow-up study of a randomized, controlled trial, Fred Saad, M.D., of the Hôpital Notre-Dame in Montréal, and colleagues found that long-term treatment with zoledronic acid reduced skeletal-related events, such as fractures and spinal cord compression.
Contact: Sylvie Dagenais, Hôpital Notre-Dame, 514-890-8000 x27466, sylvie.dagenais@ssss.gouv.qc.ca
Also in the June 2 JNCI:
- Male and Female Smokers Have Similar Lung Cancer Risk: http://www.eurekalert.org/emb_releases/2004-06/jotn-maf052604.php
- "Reduced Exposure" Tobacco Products Lessen Carcinogen Exposure, But Medicinal Nicotine Better: http://www.eurekalert.org/emb_releases/2004-06/jotn-et052604.php
- Study Measures Risks of Exclusive Pipe Smoking: http://www.eurekalert.org/emb_releases/2004-06/jotn-smr052604.php
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oupjournals.org/.
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JNCI Journal of the National Cancer Institute