(Press-News.org) CHICAGO, IL (April 1, 2012)––At the time of diagnosis, the majority of breast cancers are categorized as estrogen-receptor positive, or hormone sensitive, which means their cancerous cells may need estrogen to grow. Patients with this type of cancer often respond favorably to treatments called aromatase inhibitors, like tamoxifen, which cause cell death by preventing estrogen from reaching the cancerous cells. Over time, however, the disease often becomes resistant to estrogen deprivation from the drugs—making treatment options more limited.
New findings that will be presented at the AACR Annual Meeting 2012 on Sunday, April 1, by researchers from Fox Chase Cancer Center in Philadelphia, identify a pair of proteins that could play a crucial role in restoring treatment sensitivity to these resistant cancerous cells—possibly leading to more treatment options in the future.
In experiments on cancer cell lines, Joan Lewis-Wambi, Ph.D., a tumor biologist at Fox Chase and lead author on the study, found that the two proteins, called STAT-1 and PLSCR-1, were 10 and 20 times more abundant respectively in breast cancer cells that are resistant to estrogen deprivation than in cancerous cells that died without estrogen. The researchers also showed that the treatment-resistant cancerous cells underwent apoptosis, or cell death, in the presence of estrogen—which suggests the hormone has a complicated relationship with breast cancer.
"Breast cancer cells that are hormone dependent need estrogen to grow," says Lewis-Wambi. "But these resistant cells have the opposite response to estrogen—instead of stimulating growth, estrogen actually induces death."
Lewis-Wambi says she and her colleagues are trying to understand the complex relationship between estrogen and the behavior of these cancerous cells. In further experiments, they found increased levels of the two proteins when estrogen caused apoptosis in the cancerous cells. Previous experiments have shown that the proteins are also associated with inteferon-alpha, a protein that promotes cell death and is often used to treat solid tumors.
The new findings suggest that a therapy that uses estrogen, along with interferon-alpha, may offer a treatment option for patients whose disease is resistant to estrogen-depriving drugs. Such a treatment may use the two proteins to successfully induce the cancerous cells to undergo cell death.
"The models we've developed in the lab are reflective of what happens in the clinic when you have patients with hormone-dependent disease," says Lewis-Wambi. "Initially they respond to treatment, but over time the disease becomes resistant to the drug, and the drug no longer works."
Previous studies have suggested that the STAT-1 and PLSCR-1 proteins help induce cell death, but their exact functions have remained a mystery. Lewis-Wambi and her colleagues, including researchers from the University of Rochester, suspected that the proteins might help explain how interferon-alpha works in a cell. The researchers studied the proteins using cancer cells that were originally estrogen-receptor positive but, over time, developed resistance to drugs that starved them of estrogen.
Lewis-Wambi says that they're now following up their promising in vitro results with in vivo experiments to see if the proteins behave similarly in animal models. Once they can demonstrate the results in animals, the scientists can think about how their work might influence treatment.
In addition to suggesting an interferon- and estrogen-based treatment, the proteins may help identify patients most likely to respond to a particular kind of therapy. This kind of personalized cancer treatment, based on the molecular biology of a person's disease rather than the site or size of the tumor, has the potential to be more effective and have fewer side effects than conventional chemotherapies.
"We know that no two patients are the same," Lewis-Wambi says. "One drug may work perfectly well in one patient but have no effect in another. That comes back to the fact that a tumor's molecular profile looks different from one individual to another. Our goal is to identify the genes that make patients more or less likely to respond to a drug. Then you're treating the individual, as opposed to the group."
INFORMATION:
Co-authors on the study include Charlene Brewer, Rifat Jan, Annalese Smith, and Tabitha King from Fox Chase Cancer Center, and Peter Sims from the University of Rochester in Rochester, New York.
The study was supported in part by an NIH career development grant and the Hollenbach Foundation Grant.
Fox Chase Cancer Center is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, visit Fox Chase's Web site at www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427).
END
A new study contrasting ocean temperature readings of the 1870s with temperatures of the modern seas reveals an upward trend of global ocean warming spanning at least 100 years.
The research led by Scripps Institution of Oceanography at UC San Diego physical oceanographer Dean Roemmich shows a .33-degree Celsius (.59-degree Fahrenheit) average increase in the upper portions of the ocean to 700 meters (2,300 feet) depth. The increase was largest at the ocean surface, .59-degree Celsius (1.1-degree Fahrenheit), decreasing to .12-degree Celsius (.22-degree Fahrenheit) at ...
In April 1947 the post-war Labour Government raised the school leaving age from 14 to 15 and paved the way for a further increase to 16 in 1972. Now, 65 years later, as the UK prepares to raise the 'education participation age' to 17 in 2013 and to 18 in 2015, new research reveals that the transitions of 1947 and 1972 met with more controversy and difficulty than previously thought.
In a study funded by the Economic and Social Research Council, Dr Tom Woodin and Professor Gary McCulloch of the Institute of Education, London, analysed the debate surrounding the implementation ...
WASHINGTON – Fishing for herring, anchovy, and other "forage fish" in general should be cut in half globally to account for their critical role as food for larger species, recommends an expert group of marine scientists in a report released today. The Lenfest Forage Fish Task Force conducted the most comprehensive worldwide analysis of the science and management of forage fish populations to date. Its report, "Little Fish, Big Impact: Managing a crucial link in ocean food webs," concluded that in most ecosystems at least twice as many of these species should be left in ...
Bethesda, MD -- A new discovery in mice may lead to new treatments that could make bone marrow transplants more likely to succeed and to be significantly less dangerous. According to new research findings published in the Journal of Leukocyte Biology (https://www.jleukbio.org) Brazilian scientists may have found a way to prevent the immune system from attacking transplant grafts and damaging the host's own cells after a bone marrow transplant.
Specifically, they found that a receptor for a mediator of the inflammatory process, known as platelet activating factor plays ...
CHAPEL HILL, N.C. -- University of North Carolina at Chapel Hill researchers working as part of the International Cystic Fibrosis Consortium have discovered several regions of the genome that may predispose cystic fibrosis (CF) patients to develop an intestinal blockage while still in the uterus.
A report of this international study appears online April 1, 2012 in the journal Nature Genetics. It was the work of the North America CF Gene Modifier Consortium, which brought together dozens of investigators from the United States, Canada, and from France, to identify genetic ...
Picky females play a critical role in the survival and diversity of species, according to a Nature study by researchers from the University of British Columbia and the International Institute for Applied Systems Analysis (IIASA) in Austria.
To date, biodiversity theories have focused on the role played by adaptations to the environment: the species best equipped to cope with a habitat would win out, while others would gradually go extinct. The new study presents the first theoretical model demonstrating that selective mating alone can promote the long-term coexistence ...
Scientists at Washington University School of Medicine in St. Louis are using powerful DNA sequencing technology not only to identify mutations at the root of a patient's tumor – considered key to personalizing cancer treatment – but to map the genetic evolution of disease and monitor response to treatment.
"We're finding clinically relevant information in the tumor samples we're sequencing for discovery-oriented research studies," says Elaine Mardis, PhD, co-director of The Genome Institute at the School of Medicine. "Genome analysis can play a role at multiple time ...
Minor accidents take place every single day in Southern California. These ordeals can often be resolved with the assistance of an insurance company and a fair settlement that is going to quickly pay for injuries, damage to property, or any other associated costs. When drivers are not receiving the financial assistance that they need in order to pay for serious or ongoing medical expenses though, it will not take much for the situation to enhance into a messy legal situation. In order to assist victims, the leading Los Angeles personal injury lawyer, Farhad Hamdam, is now ...
Bethesda, MD—If you're expecting, this might make you feel a little better about reaching for that pint of ice cream: New research published online in the FASEB Journal (http://www.fasebj.org) suggests that twins, and babies of mothers who diet around the time of conception and in early pregnancy, may have an increased risk of obesity and type 2 diabetes throughout their lives. This study provides exciting insights into how behavior can lead to epigenetic changes in offspring related to obesity and disease.
"This study may provide a new understanding of why twins can ...
CHICAGO - Four proteins involved in translation, the final step of general protein production, are associated with poor prognosis in hormone-receptor-positive breast cancer when they are dysregulated, researchers reported at the AACR Annual Meeting 2012.
All of the aberrantly activated translational proteins are regulated by the PI3K/mTOR molecular signaling pathway, which has been implicated in development and progression of several cancers.
More recently, mTOR activation has been tied to resistance to standard endocrine therapy in estrogen-receptor positive breast ...
