Researchers at the Indiana University School of Medicine have discovered a highly accurate, non-invasive test to identify benign pancreatic cysts, which could spare patients years of nerve-racking trips to the doctor or potentially dangerous surgery.
The test, which analyses fluid from pancreatic cysts, can identify a common type of benign cyst that can’t be differentiated by imaging alone from cysts that may progress to pancreatic cancer.

Pancreatic cyst fluid is tested for a biomarker, a specific isoform of vascular endothelial growth factor A, or VEGF-A. Pancreatic cyst fluid is often obtained in patients with pancreatic cysts as a part of standard testing during endoscopy. High levels of VEGF-A indicate with 99 percent accuracy that the cyst will not become malignant, the researchers found after analysing the results of 87 patients.

First author Michele T. Yip-Schneider, Ph.D., associate research professor of surgery, and senior author C. Max Schmidt, M.D., Ph.D., MBA, professor of surgery, biochemistry and molecular biology, report this is the first cyst fluid protein biomarker that can differentiate serious cystic neoplasms, a benign type of cystic lesion, from all other cancerous or pre-cancerous cystic lesions without surgery.

Pancreatic cancer is one of the deadliest cancers in part because it is frequently diagnosed late and treatment options are somewhat limited. According to the National Cancer Institute, about 45,220 people will be diagnosed this year with pancreatic cancer and about 38,460 will die from the disease.

Treatments may include chemotherapy, radiation and surgery, but few patients are cured.

‘Only 15 percent of pancreatic cancer patients will benefit from surgery, and of those, only about 20 percent will survive five years,’ said Dr. Schmidt, who is a researcher with the Indiana University Melvin and Bren Simon Cancer Center and director of the IU Health Pancreatic Cyst and Cancer Early Detection Center.

Complications from pancreatic surgery are common and can be life threatening, so sparing a patient unnecessary surgery is important, Dr. Schmidt said.

‘As scientists, we have tried to figure out which cystic lesions are benign, which are pre-cancerous and which are malignant,’ Dr. Yip-Schneider said. ‘Although pancreatic cysts are best seen on pancreatic MRI-MRCP, making a diagnosis of which type of cyst and how likely cancer will develop is not usually possible through imaging alone.’

Surgery is not the panacea that patients frequently hope for, and the majority of pancreatic cancer patients aren’t even eligible due to the advanced stage of the disease at presentation.

Pancreatic cysts and cancer are becoming more common in the American population. It is unclear why, but pancreatic cancer is clearly associated with obesity, smoking and a family history of pancreatic cancer.

Today, about 3 percent of the U.S. population has pancreatic cysts, although many are asymptomatic and go undiagnosed. Most of these cysts are pre-cancerous, but some are completely benign while others are cancerous. Patients go through extensive follow-up medical visits, invasive biopsies and sometimes unnecessary surgery to determine the true nature of their pancreatic cyst. The novel marker VEGF-A can completely eliminate the need for this extensive follow-up and potential harm for patients with unrecognized benign cysts, the researchers said.

‘Many of my patients when initially told they have pancreatic cysts are very fearful and ask for surgical removal of the cyst or the entire pancreas before they even learn their options,’ Dr. Schmidt said. ‘Now, physicians will have an outpatient procedure to offer that can take some of the guesswork out of the equation.’ Indiana University

Researchers at the Sahlgrenska Academy have identified a gene, which explains why certain patients with chronic hepatitis C do not experience relapse after treatment. The discovery may contribute to more effective treatment.
More than 100 million humans around the world are infected with hepatitis C virus. The infection gives rise to chronic liver inflammation, which may result in reduced liver function, liver cirrhosis and liver cancer. Even though anti-viral medications often efficiently eliminate the virus, the infection recurs in approximately one fifth of the patients.
Martin Lagging and co-workers at the Sahlgrenska Academy have studied an enzyme called inosine trifosfatase (ITPase), which normally prevents the incorporation of defective building blocks into RNA and DNA.
Unexpectedly they found that the gene encoding for ITPase (ITPA) had significance for the treatment outcome in chronic hepatitis C virus infection.
Earlier studies had shown that approximately one third of all people carry variants of the ITPA gene that result in reduced ITPase activity. The research team at the Sahlgrenska Academy showed that patients with these gene variants exhibited a more than a five times lower risk of experiencing relapse after treatment.
The study encompassed over 300 patients and was carried out in co-operation with hepatitis researchers in several Nordic countries.
Relapse after completed treatment is a significant problem in chronic hepatitis C, and the results may contribute to explaining why the infection recurs in many patients. Our hypothesis is that a low ITPase activity results in defective nucleotides being incorporated into the virus RNA, which makes the virus unstable, Martin Lagging said.
According to Martin Lagging, the discovery may also have significance for other virus infections.
A medication that interferes with the enzyme’s activity could have a broad antiviral effect, but this must be further investigated in future studies. University of Gothenburg

For more than 100 years, researchers have been unable to explain why cancer cells contain abnormal numbers of chromosomes, a phenomenon known as aneuploidy. Many believed aneuploidy was simply a random by-product of cancer.

Now, a team at Harvard Medical School has devised a way to understand patterns of aneuploidy in tumours and predict which genes in the affected chromosomes are likely to be cancer suppressors or promoters. They propose that aneuploidy is a driver of cancer rather than a result of it.
‘If you look at a cancer cell, it looks like an unholy mess with gene deletions and amplifications, chromosome gains and losses, like someone threw a stick of dynamite into the cell. It seems random, but actually previous work has shown that there is a pattern to which chromosomes and chromosome arms are altered—and that means we can understand that pattern and how or if it drives cancer,’ said senior author Stephen Elledge, Gregor Mendel professor of Genetics and of Medicine at HMS and professor of medicine at Brigham and Women’s Hospital.

‘What we have done is to propose a new theory about how this works and then prove it using mathematical analysis,’ he said.
For decades since the ‘oncogene revolution,’ cancer research has focused on mutations—changes in the DNA code that abnormally activate genes that promote cancer, called oncogenes, or deactivate genes that suppress cancer. The role of aneuploidy—in which entire chromosomes or chromosome arms are added or deleted—has remained largely unstudied.

Elledge and his team, including research fellow and first author Teresa Davoli, suspected that aneuploidy has a significant role to play in cancer because missing or extra chromosomes likely affect genes involved in tumour-related processes such as cell division and DNA repair.

To test their hypothesis, the researchers developed a computer program called TUSON (Tumour Suppressor and Oncogene) Explorer together with Wei Xu and Peter Park at HMS and Brigham and Women’s. The program analysed genome sequence data from more than 8,200 pairs of cancerous and normal tissue samples in three pre-existing databases.

They generated a list of suspected oncogenes and tumour suppressor genes based on their mutation patterns—and found many more potential cancer drivers than anticipated. Then they ranked the suspects by how powerful an effect their deletion or duplication was likely to have on cancer development.

Next, the team looked at where the suspects normally appear in chromosomes.

They discovered that the number of tumour suppressor genes or oncogenes in a chromosome correlated with how often the whole chromosome or part of the chromosome was deleted or duplicated in cancers. Where there were concentrations of tumour suppressor genes alongside fewer oncogenes and fewer genes essential to survival, there was more chromosome deletion. Conversely, concentrations of oncogenes and fewer tumour suppressors coincided with more chromosome duplication.

When the team factored in gene potency, the correlations got even stronger. A cluster of highly potent tumour suppressors was more likely to mean chromosome deletion than a cluster of weak suppressors.
Since 1971, the standard tumor suppressor model has held that cancer is caused by a ‘two-hit’ cascade in which first one copy and then the second copy of a gene becomes mutated. Elledge argues that simply losing or gaining one copy of a gene through aneuploidy can influence tumour growth as well.

‘The loss or gain of multiple cancer driver genes that individually have low potency can add up to have big effects,’ he said.

‘It’s a terrific study,’ said Angelika Amon, a professor of biology at Massachusetts Institute of Technology who was not involved in the project. ‘These novel algorithms of identifying tumour suppressors and oncogenes nicely provide an explanation of how aneuploidies evolve in cancer cells, and the realisation that subtle changes in the activity of many different genes at the same time can contribute to tumorigenesis is an exciting and intriguing hypothesis.’

These findings also may have answered a long-standing question about whether aneuploidy is a cause or effect of cancer, leaving researchers free to pursue the question of how. Harvard Medical School

A team of researchers from UCLA’s Henry Samueli School of Engineering and Applied Science has developed a Google Glass application and a server platform that allow users of the wearable, glasses-like computer to perform instant, wireless diagnostic testing for a variety of diseases and health conditions.
With the new UCLA technology, Google Glass wearers can use the device’s hands-free camera to capture pictures of rapid diagnostic tests (RTDs), small strips on which blood or fluid samples are placed and which change colour to indicate the presence of HIV, malaria, prostate cancer or other conditions. Without relying on any additional devices, users can upload these images to a UCLA-designed server platform and receive accurate analyses — far more detailed than with the human eye — in as little as eight seconds.
The new technology could enhance the tracking of dangerous diseases and improve public health monitoring and rapid responses in disaster-relief areas or quarantine zones where conventional medical tools are not available or feasible, the researchers said.
‘This breakthrough technology takes advantage of gains in both immunochromatographic rapid diagnostic tests and wearable computers,’ said principal investigator Aydogan Ozcan, the Chancellor’s Professor of Electrical Engineering and Bioengineering at UCLA and associate director of UCLA’s California NanoSystems Institute. ‘This smart app allows for real-time tracking of health conditions and could be quite valuable in epidemiology, mobile health and telemedicine.’
In addition to designing the custom RDT–reader app for Google Glass, Ozcan’s team implemented server processes for fast and high-throughput evaluation of test results coming from multiple devices simultaneously. Finally, the researchers developed a web portal where users can view test results, maps charting the geographical spread of various diseases and conditions, and the cumulative data from all the tests they have submitted over time.
To submit images for test results, Google Glass users only need to take photos of RTD strips or other commonly available in-home tests, then upload the images wirelessly through the device to the UCLA-designed web portal. The technology permits quantified reading of the results to a few-parts-per-billion level of sensitivity — far greater than that of the naked eye — thus eliminating the potential for human error in interpreting results, which is a particular concern if the user is a health care worker who routinely deals with many different types of tests.
To gauge the accuracy and efficiency of the technology, the UCLA team used an in-home HIV test designed by OraSure Technologies and a prostate-specific antigen test made by JAJ International. The researchers took images of tests under normal, indoor, fluorescent-lit room conditions. They submitted more than 400 images of the two tests, and the RDT reader and server platform were able to read the images 99.6 percent of the time. In every case in which the technology successfully read the images, it returned accurate and quantified test results, according to the team.
The researchers also tested more than 300 blurry images or images of the testing device taken under various natural-usage scenarios and achieved a read rate of 96.6 percent. The UCLA Henry Samueli School of Engineering and Applied Science