Cigarette smoke is the dominant cause of lung cancer in the United States, accounting for an estimated 90 percent of all cases. While only 10-20 percent of smokers develop lung cancer in their lifetime, there are currently no tools available to identify which of the approximately 90 million current and former smokers in the U.S. are at the highest risk.
Unfortunately, diagnosis is most often made at a very advanced stage where treatment is largely ineffective. The damage caused by cigarette smoke, however, is not limited solely to the lung, but rather constitutes a 'field of injury' throughout the entire respiratory tract that is exposed to the toxin. Consistent with this idea, study lead author Avrum Spira, MD, MSc, chief of the section of computational biomedicine in the department of medicine at BUSM and his colleagues, previously developed a gene expression-based biomarker measured in the cytologically normal bronchial airway epithelium that reflects an individual's physiologic response to smoking and distinguishes smokers with and without lung cancer. Although this biomarker is successful at diagnosing lung cancer, it does not identify the signaling pathways underlying these gene expression changes.
Using a novel gene-expression based approach to define oncogenic pathway signatures, the researchers, in collaboration with Dr. Andrea Bild at the University of Utah, have now discovered that the expression of genes belonging to one specific cancer-related pathway, PI3K, are activated in the cells that line the airway of smokers with lung cancer. This gene expression activity in the normal cells of the proximal airway precedes the development of lung cancer and may be reversed with a specific chemopreventive agent (myo-inositol) that targets this pathway.
"This finding is significant as these cells can be obtained in a relatively non-invasive fashion from the airway of smokers at risk for lung cancer, and does not require invasive sampling of lung tissue where lung tumors normally arise," said Spira, who is also an associate professor medicine and pathology at BUSM.
The BUSM researchers then went on to validate their findings by measuring the biochemical activity of this pathway in the airway epithelial cells from an independent group of smokers with and without lung cancer. "We found that this PI3K pathway gene expression activity is decreased in the airway of high-risk smokers who had regression (or improvement) of their premalignant lesions following treatment with a potential lung cancer chemopreventive agent known as myo-inositol, and demonstrated that myo-inositol inhibits the PI3K pathway in lung cancer cell lines," he added.
According to the researchers, the data suggests that measuring this airway gene expression activity can help determine which specific cancer pathways have been deregulated within an individual smoker, allowing one to tailor a specific drug that will target the pathway to reduce that individual's risk of lung cancer. "This represents a critical advance in the field of lung cancer prevention as there are currently no effective strategies for lung cancer prevention among high risk smokers. Our work has the potential to help address the enormous and growing public health burden associated with lung cancer, the leading cause of cancer-related death among men and women in the US and the world," added Spira.
Funding for this study was provided by the National Institutes of Health.
Spira is one of the founders of Allegro Diagnostics Inc., a molecular diagnostics company that plans to market the gene expression biomarker.
Gina DiGravio | EurekAlert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering