People who are dementia-free but have two parents with Alzheimer’s disease may show signs of the disease on brain scans decades before symptoms appear, according to a new study. ‘Studies show that by the time people come in for a diagnosis, there may be a large amount of irreversible brain damage already present,’ said study author Lisa Mosconi, PhD, with the New York University School of Medicine in New York. ‘This is why it is ideal that we find signs of the disease in high-risk people before symptoms occur.’ For the study, 52 people between the ages of 32 and 72 and free of dementia underwent several kinds of brain scans, including Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans. PET scans measure the amount of brain plaques as well as overall brain activity, such as brain metabolism. MRI scans look at brain structure and possible reductions in brain volume. Participants were split into four groups of 13 people: those with a mother with Alzheimer’s disease, a father, both parents, or no family history of the disease. People with both parents who had Alzheimer’s disease showed more severe abnormalities in brain volume, metabolism and five to 10 percent increased brain plaques in certain brain regions compared to the other three groups. ‘Our study also suggests that there might be genes that predispose individuals to develop brain Alzheimer’s pathology as a function of whether one parent or both parents have the disease,’ Mosconi said. ‘We do not yet know which genes, if any, are responsible for these early changes, and we hope that our study will be helpful to future genetic investigations.’ People whose mother had Alzheimer’s disease showed a greater level of the Alzheimer’s disease biomarkers in the brain than people whose father had the disease, which is consistent with previous studies showing that people whose mothers had the disease were more likely to develop it than those with fathers with the disease, Mosconi said. She noted the small sample size of the study. The research was supported by the National Institutes of Health and the Alzheimer’s Association. American Academy of Neurology

Findings show how a genetic mutation in untreated patients is linked to aggressive cancer later in life. It was previously thought that the mutation only occurred in response to therapy.

The research highlights why relapses could occur in some men following hormone therapy. And it could help identify those patients that will develop fatal prostate cancer much earlier for life-extending therapy.

Prostate cancer is the most common cancer in men in the UK, with more than 40,000 new cases diagnosed every year. Treatment options for patients diagnosed with early stage prostate cancer vary from ‘watchful waiting’ to hormone-withdrawal therapy, radiotherapy or surgery.

Additional tests for indicators of aggressive cancer are necessary to help categorise patients so that those with a low-risk of the disease spreading can avoid unnecessary treatment, and those diagnosed with a high-risk can be targeted for more aggressive first line therapy.

Hormone-withdrawal therapy often results in a dramatic remission, however the disease invariably relapses with a resistant form of the cancer. A third of these are due to an increase in copy number of a particular gene called the ‘androgen receptor’. The gene is on the X-Chromosome and so there is normally only one copy of this gene present in men. Prostate cancer thrives on male hormones, and one way that they develop to grow better is to increase the number of copies of the androgen receptor gene. This also enables the cancer to resist therapy.

Lead researchers Dr Jeremy Clark and Prof Colin Cooper from UEA’s school of Biological Sciences carried out the research at the Institute of Cancer Research, London, and at UEA.

Dr Clark said: ‘By the age of 60, the majority of men will have signs of prostate cancer. However, only a small proportion of men will die of the disease. The question is – which of these cancers are dangerous and which are not? Deciding which cancers are going to progress and kill the patient is key to effective patient treatment.’

‘Prostate cancer thrives on male hormones, and cutting the supply of hormones to the cancer is a main avenue of therapy. Prostate cancer only kills the patient when it becomes immune to these therapies. A third of these killer cancers are immune to therapy because they have boosted the number of male hormone receptor (AR) genes in their DNA. This gene boosting, also known as amplification, has been thought to be a response of the tumour to the hormone reduction therapy itself.

‘Our research has shown that an early form of this hormone-gene boosting is present in a number of prostate cancers that have never been treated with hormone reduction therapy. We think that it is these cancers that will grow and kill the patient.

‘This discovery can be used to identify these killer cancers in patients much earlier than is currently possible. Patients could then be selected for more aggressive therapy before the cancer has developed full immunity.’

The research team looked at biomarkers from almost 600 patients prior to hormone-withdrawal therapy. But the method of identification used was labour intensive and time consuming. Developing ways of identifying patients for early therapeutic intervention will be key to implementing this discovery in the clinic. The research team are currently looking at more rapid ways of identifying patients that will develop aggressive cancer. University of East Anglia

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

Cancer rates in developing nations have climbed sharply in recent years, and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes, but screening approaches such as mammograms and colonoscopy, used in the developed world, are too costly to be implemented in settings with little medical infrastructure.
To address this gap, MIT engineers have developed a simple, cheap, paper test that could improve diagnosis rates and help people get treated earlier. The diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person has cancer. This approach has helped detect infectious diseases, and the new technology allows non-communicable diseases to be detected using the same strategy.
The technology, developed by MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, relies on nanoparticles that interact with tumour proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient’s urine.
‘When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis,’ says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. ‘For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.’
　
In 2012, Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumour proteins that would be hard to detect on their own. These proteins, known as matrix metalloproteinases (MMPs), help cancer cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.
The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumour sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.
In the original version of the technology, these peptides were detected using an instrument called a mass spectrometer, which analyses the molecular makeup of a sample. However, these instruments are not readily available in the developing world, so the researchers adapted the particles so they could be analysed on paper, using an approach known as a lateral flow assay — the same technology used in pregnancy tests.
To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.
In tests in mice, the researchers were able to accurately identify colon tumours, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients. MIT

The Icahn School of Medicine at Mount Sinai announced the launch of a more accurate carrier screening test for spinal muscular atrophy (SMA), one of the most common and severe autosomal recessive disorders. This new test will help prospective parents more effectively identify whether they carry the mutation that will affect their offspring. The test screens for genetic variation discovered by Mount Sinai researchers, which has been demonstrated to identify silent carriers of SMA in certain populations with higher accuracy and offers more accurate risk estimates than existing tests in all ethnic groups tested. Mount Sinai will be licensing the new test to other clinical laboratories to facilitate access to more accurate SMA carrier screening for as many people as possible.
SMA is an autosomal recessive disease that affects about 1 in 10,000 people and is one of the most deadly genetic diseases among infants and toddlers. It is transmitted by carrier parents who have no symptoms themselves; as many as 1 in 35 people may carry an SMN1 gene mutation, which is the gene that is defective in SMA. The disease kills nerve cells in the spinal cord, causing progressive degeneration among patients and diminishing capacity for walking, breathing, and swallowing. Severe forms of SMA are fatal, and there is currently no cure for the disease.
Scientists at the Mount Sinai Genetic Testing Laboratory recently used next-generation DNA sequencing to discover a new SMN1 genetic pattern that more accurately predicts the risk of having children with this disease. Current SMA carrier screening tests may result in false negative results due to their inability to detect silent carriers with two copies of the SMN1 gene on one chromosome and no copies on the other. The Mount Sinai Genetic Testing Laboratory’s patent-pending enhanced SMA test identifies a novel haplotype that successfully distinguishes those duplicated genes. This work significantly improves detection rates in the Ashkenazi Jewish population and improves risk estimates after a negative carrier screen for SMA in all ethnic groups.
‘People who choose to undergo carrier screening for spinal muscular atrophy do so to ensure that their future children will not suffer from this debilitating disease. It is important to provide patients with the most accurate risk estimates possible,’ said Lisa Edelmann, PhD, Director of the Mount Sinai Genetic Testing Laboratory. ‘Launching this enhanced test based on our recent scientific findings on SMN1 will provide more meaningful answers to these prospective parents, and it can also provide new information to people who have previously been screened with existing SMA carrier tests.’
The new test will be performed by the Genetic Testing Laboratory for all patients undergoing carrier screening for SMA. In addition, Mount Sinai will actively license the test to as many third-party clinical laboratories as possible. Mount Sinai Health System