The University of Surrey in the UK and ZEUS Scientific, a US based global in vitro diagnostics company, announced today that they have entered into an agreement that grants ZEUS Scientific a worldwide non-exclusive license covering the development and commercialization of products utilizing ELISA and ZEUS’ multiplex technology platforms using the Engrailed-2 (EN2) protein as a patented biomarker for prostate and bladder cancer and provides a diagnostic benefit that complements conventional diagnostics in these cancer patients.  EN2 is a novel biomarker that is diagnostic of prostate or bladder cancer as it is only expressed and secreted by cancerous cells.  The University of Surrey will supply proprietary reagents to ZEUS Scientific to manufacture and market products for in vitro diagnostic testing for these cancer applications.  Financial terms of the agreement were not disclosed.  This transaction was managed by McDonald & Associates, a global transaction and strategic consultancy, as advisor to the University of Surrey Technology Transfer Office.
“ZEUS Scientific is excited to execute this agreement with the University of Surrey”, noted Scott Tourville, CEO of ZEUS Scientific. “This represents ZEUS Scientific’s continued expansion into the diagnostics of cancer and other diseases using novel biomarkers that have strong scientific data supporting their clinical utility”.  ZEUS plan to CE mark this test and submit to the USFDA in 2014.  
“The University of Surrey is looking forward very much to working with Zeus to introduce EN2 as a novel diagnostic test for prostate and bladder cancers”, commented Professor Hardev Pandha MD, PhD, Professor of Medical Oncology, University of Surrey, and Consultant Medical Oncologist, Royal Surrey County Hospital. “In prostate cancer our studies have shown that the EN2 test does not need prostatic massage and that levels of EN2 correlate strongly with disease volume. Knowledge of disease volume may help the urologist assess whether the patient has a small volume of disease that may be safely and actively monitored or a larger volume that needs to be treated.”  

www.zeusscientific.com

A multi-institutional team of researchers have pinpointed the genetic traits of the cells that give rise to gliomas – the most common form of malignant brain cancer. The findings provide scientists with rich new potential set of targets to treat the disease.
‘This study identifies a core set of genes and pathways that are dysregulated during both the early and late stages of tumour progression,’ said University of Rochester Medical Center (URMC) neurologist Steven Goldman, M.D., Ph.D., the senior author of the study and co-director of the Center for Translational Neuromedicine. ‘By virtue of their marked difference from normal cells, these genes appear to comprise a promising set of targets for therapeutic intervention.’
As its name implies, gliomas arise from a cell type found in the central nervous system called the glial cell. Gliomas progress in severity over time and ultimately become highly invasive tumours known as glioblastomas, which are difficult to treat and almost invariably fatal. Current treatments, which include surgery, radiation therapy, and chemotherapy, can delay disease progression, but ultimately prove ineffective.
Cancer research has been transformed over the past several years by new concepts arising from stem cell biology. Scientists now appreciate that many cancers are the result of rogue stem cells or their offspring, known as progenitor cells. Traditional cancer therapies often do not prevent a recurrence of the disease since they may not effectively target and destroy the cancer-causing stem cells that lie at the heart of the tumours.
Gliomas are one such example. The source of the cancer is a cell found in the brain called the glial progenitor cell. The cells, which arise from and maintain characteristics of stem cells, comprise about three percent of the cell population of the human brain. When these cells become cancerous they are transformed into glioma stem cells, essentially glial progenitor cells whose molecular machinery has gone awry, resulting in uncontrolled cell division.
Goldman and his team have long studied normal glial progenitor cells. These cells produce glia, a category that includes both astrocytes – cells that support the function of neurons – and oligodendrocytes – cells that produces myelin, the fatty insulation that allows the long-distance conduction of neural impulses.
While Goldman’s group’s work has primarily focused on ways to use glial progenitor cells to treat neurological disorders such as multiple sclerosis, their understanding of the biology of these cells and mastery of the techniques required to sort, identify, and isolate these cells has also enabled them to explore the molecular and genetic changes that transform these cells into cancers.
Using human tissue samples representing the three principal stages of the cancer, the researchers were able to identify and isolate the cancer-inducing stem cells. Working with Goldman, lead authors Romane Auvergne, Ph.D. and Fraser Sim, Ph.D. then compared the gene expression profiles of these cancer stem cells to those of normal glial progenitor cells. The objective was to both pinpoint the earliest genetic changes associated with cancer formation and identify those genes that were unique to the cancer stem cells and were expressed at every stage of disease progression.
Out of a pool over 44,000 tested genes and sequences, the scientists identified a small set of genes in the cancerous glioma progenitor cells that were over-expressed at all stages of malignancy. These genes formed a unique ‘signature’ that identified the tumour progenitor cells and enabled the scientists to define a corresponding set of potential therapeutic targets present throughout all stages of the cancer.
‘One of the key things you are looking for in drug development in cancer is a protein or gene that is over-expressed, so that you can attempt to achieve therapeutic benefit by inhibiting it,’ said Goldman.
The researchers chose to test this hypothesis by targeting one such gene, called SIX1, which was highly over-expressed in the glioma progenitor cells. While this particular gene is active in the early development of the nervous system, it had not been observed in the adult brain before. However, SIX1 signalling has been associated with breast and ovarian cancer, raising the possibility of its contribution to brain cancer as well. This turned out to indeed be the case. When the researchers blocked – or knocked down – the expression of this gene, the tumour cells ceased growing, and implanted tumours shrank.
‘This study gives us a blueprint to develop new therapies,’ said Goldman. ‘We can now devise a strategy to systematically and rationally analyse – and eliminate – glioma stem and progenitor cells using compounds that may selectively target these cells, relative to the normal glial progenitors from which they derive. By targeting genes like SIX1 that are expressed at all stages of glioma progression, we hope to be able to effectively treat gliomas regardless of their stage of malignancy. And by targeting the glioma-initiating cells in particular, we hope to lessen the likelihood of recurrence of these tumours, regardless of the stage at which we initiate treatment.’ University of Rochester Medical Center

​Can the length of strands of DNA in patients with heart disease predict their life expectancy?
Researchers from the Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City, who studied the DNA of more that 3,500 patients with heart disease, say yes it can.
In the new study, the researchers were able to predict survival rates among patients with heart disease based on the length of strands of DNA found on the ends of chromosomes known as telomeres—the longer the patient’s telomeres, the greater the chance of living a longer life.
Previous research has shown that telomere length can be used as a measure of age, but these expanded findings suggest that telomere length may also predict the life expectancy of patients with heart disease.

Telomeres protect the ends of chromosome from becoming damaged. As people get older, their telomeres get shorter until the cell is no longer able to divide. Shortened telomeres are associated with age-related diseases such as heart disease or cancer, as well as exposure to oxidative damage from stress, smoking, air pollution, or conditions that accelerate biologic ageing.

‘Chromosomes by their nature get shorter as we get older,’ said John Carlquist, PhD, director of the Intermountain Heart Institute Genetics Lab. ‘Once they become too short, they no longer function properly, signalling the end of life for the cell. And when cells reach this stage, the patient’s risk for age-associated diseases increases dramatically.’

Dr. Carlquist and his colleagues from the Intermountain Heart Institute at Intermountain Medical Center tested the DNA samples from more than 3,500 heart attack and stroke patients.

‘Our research shows that if we statistically adjust for age, patients with longer telomeres live longer, suggesting that telomere length is more than just a measure of age, but may also indicate the probability for survival. Longer telomere length directly correlate with the likelihood for a longer life—even for patients with heart disease,’ said Dr. Carlquist. Intermountain Medical Center Heart Institute

Researchers from the Masonic Cancer Center, University of Minnesota, and the University’s Brain Tumor Program, have developed a new mouse model of malignant peripheral nerve sheath tumours (MPNST) that allow them to discover new genes and gene pathways driving this type of cancer.
Utilising the Sleeping Beauty transposon method, researchers in the lab of David Largaespada, Ph.D., professor in the Medical School and College of Biological Sciences, were able to use an unbiased approach to generate mouse models of MPNST development that lead to the identification of genes related to this tumour’s development.

MPNST is a genetically diverse, aggressive form of sarcoma impacting connective tissue surrounding nerves that occurs sporadically or in association with Neurofibromatosis Type 1 (NF1) syndrome. The exact cause of MPNST is not known, but symptoms include swelling in the arms and legs, soreness and stiffness at the site of the tumour. MPNSTs are the most common malignancy in adults with NF1 syndrome and leading cause of NF1-related mortality.

Due to the invasive nature and high incidence of metastasis of MPNSTs, surgical resection, radiotherapy and chemotherapeutic treatments have proven to be ineffective for long-term treatment, resulting in 5-year survival rates of less than 25 percent with metastatic disease.

One of the most surprising findings in this research showed the gene FOXR2 is intrinsically linked to the growth of MPNSTs. This gene has not been heavily studied as researchers had not identified a clear function of this gene.

‘By using an unbiased approach, it helped us identify FOXR2 as an important gene in MPNST development and develop experiments to pinpoint the role FOXR2 plays in maintaining the aggressive nature of these tumours,’ said Eric Rahrmann, Ph.D., the paper’s lead author and a postdoctoral fellow in the Largaespada lab. ‘When we turn off FOXR2, the growth ability of these MPNSTs drastically decreases.’

Other findings showed interesting evidence of pathways that could be viable targets for therapeutics. The activation of the Wnt signalling pathway was shown to drive MPNSTs. This pathway has been highly implicated in colon cancer but not previously linked to MPNSTs.

Researchers also found many of the MPNSTs have dual loss of the genes called NF1 and PTEN. This pairing of lost genes causes MPNST formation. Both of these genes have previously been shown as pathways related to MPNSTs but it wasn’t clear the extent to which they work together.

Now, researchers are applying these findings to the testing of therapeutics currently on the market for other drugs. This research is continuing both in the mouse model and within primary tumour settings of human cell lines.

‘We want to know if these drugs, which are not currently directed at MPNSTs, could be repurposed to provide alternate therapies for patients,’ said Largaespada.

Researchers are also looking into more direct ways to target tumours through the Wnt pathway and paired NF1 and PTEN pathways, utilising mouse models and human cell lines in the lab setting. University of Minnesota

Researchers at the University of Wisconsin-Madison have found a new way to accelerate a workhorse instrument that identifies proteins. The high-speed technique could help diagnose cancer sooner and point to new drugs for treating a wide range of conditions.
Proteins are essential building blocks of biology, used in muscle, brain, blood and hormones. If the genes are the blueprints, the proteins patterned on them are the hammers and tongs of life.

Proteins are not only numerous — humans have more than 100,000 varieties — but each one has a complex structure that determines its exact function in the biological realm. Just as tissue from cats and kangaroos can be distinguished by studying the individual ‘letters’ of their genetic codes, protein A can be distinguished from protein B by looking at the amino-acid sub-units that compose all proteins.

The fastest way to count and identify proteins is to use a mass spectrometer, a precise instrument that measures chemical compounds by mass. ‘Mass spec is an essential part of modern biology, and most people use it to look at variations in proteins,’ says Joshua Coon, a professor of chemistry and biomolecular chemistry.

Because mass spectrometers are expensive, and proteins are both numerous and ubiquitous, chemists have recently learned to double up their samples so they can, for example, compare normal tissue to diseased tissue in a single run.

Knowing how the proteins change when good tissue goes bad suggests what has gone wrong.

Now, Coon has doubled-down on the doubling-up process with a technique that has the potential to run as many as 20 samples at once. The new process has already gone to work, says Alexander Hebert, a graduate student who was first author on the new publication.

‘Working with John Denu at the Wisconsin Institute for Discovery, we are looking at mice that lived with or without caloric restriction,’ says Hebert. Caloric restriction is known to increase lifespan in many animals, and scientists are eager to unravel the biochemical pathways that explain this life extension. ‘Some of these mice have lost a certain gene related to metabolism, so we are comparing four types of tissue all at once. We can look at the brain, liver or heart, and ask, how does the abundance of proteins vary?’
Already, Coon and Hebert have performed six simultaneous analyses using the new technique; but it could actually do batches of 20, Coon says.

Key to the original doubling-up process was inserting a ‘tag’ into the amino acids that gives the proteins a slightly different mass. The tags are isotopes — chemically identical atoms that have different masses.

To prepare two samples, one would receive an amino acid containing common isotopes, and the other special, heavier isotopes. The result — proteins that are chemically identical but have different masses — can easily be identified in a mass spectrometer.

The new journal report by Coon and Hebert describes a way to use amino acids built from a broader range of isotopes that would be expected to have identical mass, but do not because some of their mass has been converted to energy to hold the atomic nuclei together. Without this energy, the positively charged proteins would repel each other and the atomic nucleus would be destroyed. The tiny loss of mass due to this conversion to binding energy can be detected in the new, ultra-precise mass spectrometers that are now installed in several labs on campus.

The mass difference in the new technique is more than 1,000 times below the mass differences in the existing doubled-up technique, but it is enough to count and identify proteins from six — and, theoretically, 20 — samples at once. The researchers applied for a patent last fall and assigned the rights to the Wisconsin Alumni Research Foundation. University of Wisconsin-Madison