The findings, reported this week in the early online edition of the Proceedings of the National Academy of Sciences, indicate that potent chemotherapy drugs that target DNA in later-stage cancers could be an effective way to treat the earliest of breast tumors.
Recent research has focused on familial breast cancers, in part because the predisposing genes have been well-characterized and women at risk can be identified, said Jean J. Latimer, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at Pitt's School of Medicine. But these cases only comprise 15 percent of the 190,000 breast cancers that are diagnosed every year.
Research on sporadic breast cancer has involved the use of available cell lines derived from late-stage tumors, but most newly diagnosed tumors in the U.S. are stage I, the earliest form of invasive disease.
"Our team is able to grow stage I breast cancer cells – before they have spread to adjacent tissues and lymph nodes – allowing us to examine the mechanisms that underlie cancer development in people who didn't inherit a faulty gene," Dr. Latimer said. "The advent of innovative tissue engineering techniques has finally made it possible for us to culture these cells to determine what has gone wrong."
In earlier work, she and her colleagues found that breast tissue does not repair everyday damage to DNA as well as other tissues, such as skin. Ultraviolet light, for example, can cause mutations, but a sophisticated system of nucleotide excision repair (NER) proteins trolls the DNA strands to identify problems and initiate repair processes. The same system repairs damage caused by many environmental carcinogens, including tobacco smoke.
"Even in healthy breast tissue, this system is only about one-fifth as effective as it is in skin," Dr. Latimer noted. "This deficiency could set the stage for sporadic cancer development, with the risk increasing with age as DNA damage accumulates."
For the study, the researchers grew and assessed 19 sporadic, stage I breast tumors placed into culture directly from surgeries to test their NER pathways. In every case, there was a deficiency in repair capacity compared to disease-free breast tissue.
"That is a remarkably consistent feature for cancers that might otherwise seem random in their genesis," Dr. Latimer noted. "We rarely see a universal rule when it comes to breast cancer, but then until now, we have rarely studied stage I disease."
Some chemotherapy drugs work especially well on cells that exhibit reduced DNA repair, but they are typically given in later-stage disease. The new findings suggest, however, that these approaches could be effective in treating early stage disease, she noted.
Co-authors include Jennifer M. Johnson, M.D., Ph.D., Crystal M. Kelly, M.D., Ph.D., Tiffany D. Miles, Ph.D., Kelly A. Beaudrey-Rodgers, M.S., Nancy A. Lalanne, B.S., Victor G. Vogel, M.D., Amal Kanbour-Shakir, M.D., Joseph L. Kelley, M.D., Ronald R. Johnson, M.D., and Stephen G. Grant, Ph.D., all of the University of Pittsburgh.
The research was funded by the National Institutes of Health, the U.S. Department of Defense, the Pennsylvania Department of Health, the Komen for the Cure Awards, and the American Cancer Society.
Anita Srikameswaran | EurekAlert!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine