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Diagnosis and treatment of disease in its early stages is often the key to success.

The 21th century saw impressive applications of engineering technology in diagnosis, as well as the application of such technology in other fields of medicine.

Electrocardiogram (testing heart function); electroencephalogram (brain); electroretinography and related techniques (vision) may be briefly mentioned. And in the category of imaging: the "classical" X-ray and its 3-dimensional development, computer tomography (CT); ultrasonic echography

Such advances continue, particularly in making such high-tech diagnostic methods more "accessible"; but more recently the most striking progress has been in biochemical detection methods. These have a long history, but have recently advanced rapidly, with the development of highly selective and specific biochemical tests which are easy to use -- sometimes so easy that they have moved out of the laboratory altogether. These have great potential in mass-screening tests; but here the problems tend to be not so much technical, but more organisational and economic.


Lung cancer:

Early Lung Cancer Detection: Optical Technology Shows Potential for Prescreening Patients at High Risk.

ScienceDaily (Oct. 9, 2010) — Researchers from Northwestern University and NorthShore University HealthSystem (NorthShore) have developed a method to detect early signs of lung cancer by examining cheek cells in humans using pioneering biophotonics technology. Early detection is critical for improving cancer survival rates. Yet, one of the deadliest cancers in the United States, lung cancer, is notoriously difficult to detect in its early stages. Now, researchers have developed a method to detect lung cancer by merely shining diffuse light on cells swabbed from patients' cheeks.

"By examining the lining of the cheek with this optical technology, we have the potential to prescreen patients at high risk for lung cancer, such as those who smoke, and identify the individuals who would likely benefit from more invasive and expensive tests versus those who don't need additional tests," said Hemant K. Roy, M.D., director of gastroenterology research at NorthShore. The optical technique is called partial wave spectroscopic (PWS) microscopy and was developed by Vadim Backman, professor of biomedical engineering at Northwestern's McCormick School of Engineering and Applied Science. Backman and Roy earlier used PWS to assess the risk of colon and pancreatic cancers, also with promising results.

The lung cancer findings are published online Oct. 5 by the journal Cancer Research. The paper will appear in print in the Oct. 15 issue. Lung cancer is the leading cause of cancer deaths in the United States. Survival rates are high with surgical resection (removal of the tumor) but only if detected at an early stage. Currently there are no recommended tests for large population screening to detect lung cancer early. The disease is already advanced by the time most lung cancer patients develop symptoms. The five-year survival rate for lung cancer patients is only 15 percent. PWS can detect cell features as small as 20 nanometers, uncovering differences in cells that appear normal using standard microscopy techniques. The PWS-based test makes use of the "field effect," a biological phenomenon in which cells located some distance from the malignant or pre-malignant tumor undergo molecular and other changes.

"Despite the fact that these cells appear to be normal using standard microscopy, which images micron-scale cell architecture, there are actually profound changes in the nanoscale architecture of the cell," Backman said. "PWS measures the disorder strength of the nanoscale organization of the cell, which we have determined to be one of the earliest signs of carcinogenesis and a strong marker for the presence of cancer in the organ." "PWS is a paradigm shift, in that we don't need to examine the tumor itself to determine the presence of cancer," added Hariharan Subramanian, a research associate in Backman's lab who played a central role in the development of the technology. After testing the technology in a small-scale trial, Roy and Backman focused the study on smokers, since smoking is the major risk factor related to 90 percent of lung cancer patients. "The basic idea is that smoking not only affects the lungs but the entire airway tract," Roy said.

The study was comprised of 135 participants including 63 smokers with lung cancer and control groups of 37 smokers with chronic obstructive pulmonary disease (COPD), 13 smokers without COPD and 22 non-smokers. The research was not confounded by the participants' demographic factors such as amount of smoking, age or gender. Importantly, the test was equally sensitive to cancers of all stages, including early curable cancers. The researchers swabbed the inside of patients' mouths, and then the cheek cells were applied to a slide, fixed in ethanol and optically scanned using PWS to measure the disorder strength of cell nanoarchitecture. Results were markedly elevated (greater than 50 percent) in patients with lung cancer compared to cancer-free smokers.

A further assessment of the performance characteristics of the "disorder strength" (as a biomarker) showed greater than 80 percent accuracy in discriminating cancer patients from individuals in the three control groups. "The results are similar to other successful cancer screening techniques, such as the pap smear," Backman said. "Our goal is to develop a technique that can improve the detection of other cancers in order to provide early treatments, much as the pap smear has drastically improved survival rates for cervical cancer."

Additional large-scale validation trials are necessary for PWS. If it continues to prove effective in clinical trials at detecting cancer early, Backman and Roy believe PWS has the potential to be used as a prescreening method, identifying patients at highest risk who are likely to benefit from more comprehensive testing such as bronchoscopy or low-dose CT scans.

Proteins in Lung Cancer Cells That May Provide Potential Drug Targets Identified
ScienceDaily (Nov. 26, 2009)
— Researchers from Boston University School of Medicine (BUSM) and the Boston University Biomedical Engineering Department have identified a number of proteins whose activation allows them to distinguish between cancer and normal cells with almost 97 percent accuracy. In addition, the BU researchers have developed a new computational strategy to analyze this data and specifically identify key biological pathways (molecular circuits) that are active in cancer and "dormant" in normal cells. The study which appears in the November 25th issue of PLoS One, should ultimately lead to the development of drugs specifically aimed to inhibit these proteins. According to the BU researchers, there are many features that make cancer cells different from normal cells. They look different histologically, they proliferate and divide at different rates, they are immortal unlike normal cells, and are less communicative with their neighbor cells. They are also more "selfish" in refusing to commit suicide (programmed cell death) which normal cells do when their genomes become unstable. Much of the cellular machinery involved with these biological processes is controlled by a command control and communication system called signal transduction. Signal transduction is in large part controlled by a process called phosphorylation. When a protein is phosphorylated it either becomes active or repressed depending on its special function. "Therefore, identifying the phosphorylation status of proteins in cancer cells versus normal cells provides us with a unique ability to understand and perhaps intervene with the command and control center of cancer cells," said co-senior author Simon Kasif, PhD, who is the co-director of the Center of Advanced Genomic Technology and a professor in the department of biomedical engineering at BU. "Drugs are most effective on cancers when they attack the proteins that are activated," he added. While cancers are highly heterogeous in their make-up, the BU researchers believe that a drug that would target this collection of proteins would be effective treatment for most lung cancers. "This is the first statistically validated phosphopeptide signature to diagnose any disease, much less cancer or lung cancer," explained senior co-author Martin Steffen, MD, PhD, an assistant professor of pathology and laboratory medicine at BUSM, and director, Proteomics Core Facility at BUSM. This research was performed in collaboration with Cell Signaling Technology employing their Phosphoscan "test kit". A follow-up study is currently underway at BU to identify which cancers respond or not respond to existing cancer drugs based on the results of this test. Funding for this study was provided by the National Human Genome Research Institute and the American Lung Association.

 
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