New Screening Protocol Identifies More Case of Lynch Syndrome
A new way to select patients for further testing may increase detection of Lynch syndrome, a disorder that predisposes people to developing colorectal cancer at a young age.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is caused by mutations in DNA mismatch repair genes, the genes that fix errors that occur during DNA replication.
Kristina Lagerstedt Robinson, Ph.D., of the Karolinska University Hospital in Stockholm, and her colleagues selected a group of 285 families who had been referred to the Karolinska University Hospital for genetic counseling between 1990 and 2005 because they were at high risk for HNPCC. From those families, 112 patients were screened for mutations in mismatch repair genes, often a telltale sign of HNPCC. The screening procedure detected these mutations in 69 patients and also identified at least 57 HNPCC patients, several of whom would not have been screened under current testing practices.
"Although a population-based mutation-screening strategy has the potential to also identify nonfamilial HNPCC patients, more patients will need to be screened," the authors write. "…The most important advantage with the family history-based selection process we used is that non-HNPCC families are also identified and can be offered preventive programs."
In a related editorial, Henry Lynch, MD, of Creighton University School of Medicine in Nebraska, and his colleagues discuss the progress that has been made in diagnosing HNPCC, as well as the limitations of current selection for testing.
Contact:
- Article: Annika Lindblom, Karolinska University Hospital, annika.lindblom@ki.se
- Editorial: Kathryn Clark, public relations coordinator, Creighton University, (402) 280-2864, kathrynclark@creighton.edu
Lower Dosing Regimens of Bisphosphonates Show Antitumor Effects in Mice
Continuous treatment with low doses of bisphosphonates, a class of drugs used to strengthen bones, has been shown to inhibit the growth of skeletal tumors in mice.
Previous evidence suggested that, at high doses, bisphosphonates have antitumor properties in animal models. But these levels are considered too high for use in patients. Lower doses that are approved for treating patients have not shown adequate tumor-fighting properties.
In a new study, Florence Daubiné, M.Sc., of Inserm (the French National Institute of Health and Medical Research) in Lyon, and her colleagues tested two types of bisphosphonates—clodronate and zoledronic acid—for their effectiveness at preventing and treating skeletal tumors in mice. The mice were given daily, weekly, or single doses of the drugs either before or after they were injected with human breast cancer cells, then compared with a control group of mice that was given placebo.
A daily dose of zoledronic acid was the most effective method for preventing tumor growth, resulting in tumors that were 88% smaller than those in the control group, followed by weekly zoledronic acid (80%) and daily clodronate (50%). There was no difference in tumor size in mice given a single dose of zoledronic acid.
Contact:
Priscille Riviere, Inserm, +33 1 44 23 60 97, priscille.riviere@tobiac.inserm.fr
KISS1 Protein Required for Metastasis Suppression
A new study finds that the secretion of a protein known as KISS1 reduces metastasis of cells that express it to multiple organs in mice, but the mechanism for this continues to elude researchers.
The KISS1 protein also plays a role in sexual maturation when it is secreted and then processed into smaller peptides called kisspeptins, which in turn bind to a receptor known as GPR54. Kevin Nash, Ph.D., in the laboratory of Danny R. Welch, Ph.D., of the University of Alabama at Birmingham, and their colleagues wondered if the GPR54 receptor was also involved in metastasis suppression.
Using a human melanoma cell line that could not express KISS1, the researchers inserted one of two forms of the KISS1 gene into the cells—coding for either an unaltered form of KISS1 or a version that could not be secreted. The cells were later injected into mice that were monitored for changes in survival rates and metastatic activity of the injected cells.
The researchers concluded that KISS1 secretion was required for metastasis suppression of the melanoma cells. Only the cells with the intact form of KISS1 secreted kisspeptins, and these cells showed less metastatic activity when they were injected into the mice than those with the altered version. Mice that were injected with the gene for the intact KISS1 protein lived much longer, on average, than the mice with the non-secretable KISS1 cells. Furthermore, KISS1 blocked the growth of tumor cells that have already spread other organs. But, the authors conclude, the GPR54 receptors did not likely play a role in this process.
“The finding that KISS1 can inhibit metastatic growth in multiple organs is a particularly important feature for an antimetastatic molecular agent,” the authors write. “Finally, the finding that KISS1 can suppress metastasis in the apparent absence of GPR54 in tumor cells opens up the possibility that additional KISS1 metastasis suppressor receptors and signaling pathways exist with the potential to be selectively targeted.”
Contact:
Hank Black, UAB Media Relations, (205) 934-8938, hblack@uab.edu
EMBARGOED FOR RELEASE: 20 FEBRUARY 16:00 EST
Also in the February 21 JNCI:
http://www.eurekalert.org/emb_releases/2007-02/jotn-cs021507.php
http://www.eurekalert.org/emb_releases/2007-02/jotn-yl021507.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.oxfordjournals.org/.
Journal
JNCI Journal of the National Cancer Institute