New test set to transform breast cancer prevention

Women who have a family history of breast cancer are set to benefit from a new genetic test at Manchester University NHS Foundation Trust (MFT) that assesses breast cancer risk, with plans for it to enter clinical practice within the next six months.

Developed by researchers at MFT and The University of Manchester, the test will accurately predict breast cancer risk in women who do not test positive for BRCA1/2 gene mutations. In some instances, it may also help to refine breast cancer risk in those with the BRCA1/2 mutations, according to research published in the Journal of Medical Genetics, and funded by the NIHR and Prevent Breast Cancer.

Breast cancer is the most common cancer affecting women. Having a parent or sibling with breast cancer makes women twice as likely to get breast cancer themselves. Mutations in the BRCA1/2 genes have been identified as a cause of hereditary cancer, but only account for 15% to 20% of the underlying inherited genetic trigger for the condition. The new genetic test assesses breast cancer risk based on genetic variations (single nucleotide polymorphisms, SNPs) in an individual’s DNA. The researchers found that mutations of 18 SNPs were indicative of breast cancer risk for women who did not carry BRCA1/2 mutations. These were found to have minimal effect in isolation, but when combined could increase or decrease breast cancer risk considerably.

The case-control study recruited 451 women (112 with BRCA1/2 mutations) with a family history of breast cancer who had developed breast cancer. The researchers compared the diagnosis of invasive breast cancer and genetic profile in the case group against that of a control group of 1,605 women (691 with BRCA1/2 mutations).

The analysis of DNA using participants’ blood samples was used to determine their individual genetic makeup. To predict an overall risk estimate, the researchers used this information, alongside other risk factors including: age at first assessment; family history of first and second-degree relatives; age at first child, first period and menopause; height and weight; and history of prior non-cancerous breast disease. Many women who were originally high risk (lifetime risk of 30% or greater) were reclassified to a lower risk where risk reducing mastectomy is not recommended. The study suggested that the number of women with BRCA1/2 mutations who currently choose to have a mastectomy could reduce by a third – from 50 to about 36 per cent.

Prevent Breast Cancer’s Predicting Risk of Cancer At Screening (PROCAS) SNP study of 10,000 women, 455 of which went on to develop breast cancer, has confirmed the accuracy of the predictions.

The study was led by Gareth Evans, Professor/ Consultant in Medical Genetics and Cancer Epidemiology at The University of Manchester and Saint Mary’s Hospital. He said: “This new test will help women at risk of familial breast cancer to make more informed decisions about their care.

“BRCA1 and BRCA2 are just part of what we should be looking for when assessing risk and in Manchester we plan to incorporate screening for these new genetic markers in clinical practice within the next six months.

“We are committed to improving cancer prevention through research and, with funding from the NIHR Manchester Biomedical Research Centre, we plan to develop new screening strategies and biomarkers for other common cancers, including womb, bowel, ovarian and prostate.”

Becky Measures, BRCA1 carrier who had a mastectomy at Wythenshawe Hospital added: “When they find that they have the BRCA1/2 gene many women fear that they have to take action immediately. The new test will give women more options and help them to make a more informed decision.”

Lester Barr, chairman of Prevent Breast Cancer, said: “With more accurate genetic testing, we can better predict a woman’s risk of developing the disease and therefore offer the appropriate advice and support, rather than a ‘one size fits all’ approach. It’s so exciting to see this additional test go into clinical practice, as it’s this more tailored method that will help us on our mission to protect future generations from breast cancer.”


Phase 1 trial finds DNA-based Zika vaccine candidate safe and effective

A new generation DNA-based Zika vaccine is the first to demonstrate both safety and the ability to elicit an immune response against Zika in humans, according to new research from the Perelman School of Medicine at the University of Pennsylvania, conducted in partnership with The Wistar Institute, Inovio Pharmaceuticals, and GeneOne Life Science. In results published 4 October 2017 in the New England Journal of Medicine, the phase 1 clinical trial showed for the first time that humans who received up to three doses of the vaccine candidate produced an immune response against Zika with minimal adverse effects, opening the door to further clinical trials for this important vaccine candidate.

The GLS-5700 vaccine is a synthetic DNA vaccine that contains the instructions for the host to mount an immune response against a specific Zika virus antigen.

“Zika virus continues to be a threat to people living in the Americas and the Caribbean,” said the study’s lead author, Pablo Tebas, MD, a professor of Infectious Diseases at Penn. “With these new results, we are one step closer to hopefully finding a way to prevent infection, which can cause serious birth defects and developmental delays in babies born to women who are infected with Zika.”

In 2015 and 2016, Zika virus spread rapidly through Brazil, the Caribbean, and into the southern United States. However, a vaccine to prevent infection has remained elusive.

Researchers in Philadelphia, along with research teams from Miami and Quebec City enrolled 40 participants in the safety trial between August and September of 2016. Two groups of 20 participants received either one or two milligram doses of the vaccine candidate intradermally at zero, four, and 12 weeks. Each dosage was followed by the delivery of small electric currents into the skin at the site of injection, known as electroporation (EP), to facilitate optimal vaccine uptake, production of the intended antigen, and immune responses.

Two weeks after participants received the third and final dose of the vaccine, 100% developed Zika-specific antibodies and 80% developed significant neutralizing antibodies against the virus. Importantly, serum from the study participants was able to protect immune-compromised mice from developing the disease after infection with Zika virus, indicating that the vaccine-induced antibodies can prevent infection and disease in vivo. No serious adverse effects were reported.

“Synthetic DNA vaccines, such as this Zika vaccine candidate our team has developed, are an important approach to preventing emerging infectious diseases,” said David Weiner, PhD, executive vice president of The Wistar Institute, director of Wistar’s Vaccine & Immunotherapy Center, and co-lead author of the study. “This novel DNA vaccine was developed and implemented in just months via a platform that has advantages in temperature stability, storage, dose, and distribution compared to most traditional vaccines, making DNA vaccines an important tool to respond quickly to curb an emerging epidemic.”


Increasing frequency of blood donation has no major side effects

Giving blood more frequently – up to every 8 weeks for men and every 12 weeks for women – has no major side effects and could help to increase blood stocks, according to the first ever randomised trial of blood donation involving more than 45000 people in England published in The Lancet. In the UK, men can donate every 12 weeks, and women every 16 weeks, but the study showed that reducing the interval between donations by 4 weeks (to every 8 weeks for men, and every 12 weeks for women) had no major impact on the donors’ quality of life, mental function or physical activity, and increased the amount of blood collected over two years by 33% (1.7 units) in men and 24% (0.85 units) in women.

However, some people who gave blood more frequently did report minor symptoms including tiredness and restless legs, and the research suggests this may have been due to giving blood.

The findings may help overcome potential risks to blood stocks, including issues attracting and retaining young donors, and increased demand caused by ageing populations. In addition, it could help to increase stocks of much-needed universal blood groups and rarer blood groups.

“This study suggests that more frequent blood donation is a feasible and safe option for donors in the UK, and gives blood services the short-term option of more frequent collection from donors if the supply falls or demand rises,” says senior author Professor John Danesh, University of Cambridge, UK. Lead author, Dr Emanuele Di Angelantonio, University of Cambridge, UK, says: “The study also showed that donors who weighed above average and those with higher initial stores of iron were able to give more blood.”

The study showed there was no difference in serious adverse events, quality of life, cognitive function or levels of physical activity between people who gave blood most and least frequently.

However, people who gave blood more frequently reported more symptoms potentially related to blood donation than those who gave blood less frequently. These symptoms included feeling faint, tired, breathless, and dizzy, and were more commonly experienced by men than women. Men also had palpitations and restless legs more often than women.


Researchers uncover ‘drain pipes’ in the brain

By scanning the brains of healthy volunteers, researchers at the US National Institutes of Health saw the first, long-sought evidence that our brains may drain some waste out through lymphatic vessels, the body’s sewer system. The results further suggest the vessels could act as a pipeline between the brain and the immune system.

“We literally watched people’s brains drain fluid into these vessels,” said Daniel S. Reich, M.D., Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study published online in eLife. “We hope that our results provide new insights to a variety of neurological disorders.”

Dr Reich is a radiologist and neurologist who primarily uses magnetic resonance imaging (MRI) to investigate multiple sclerosis and other neurological disorders which are thought to involve the immune system. Led by post-doctoral fellows, Martina Absinta, Ph.D. and Seung-Kwon Ha, Ph.D., along with researchers from the National Cancer Institute, the team discovered lymphatic vessels in the dura, the leathery outer coating of the brain.

In most of the body lymphatic vessels run alongside blood vessels. They transport lymph, a colorless fluid containing immune cells and waste, to the lymph nodes. Blood vessels deliver white blood cells to an organ and the lymphatic system removes the cells and recirculates themthrough the body. The process helps the immune system detect whether an organ is under attack from bacteria or viruses or has been injured.

In 1816, an Italian anatomist reported finding lymphatic vessels on the surface of the brain, but for two centuries, it was forgotten. Until very recently, researchers in the modern era found no evidence of a lymphatic system in the brain, leaving some puzzled about how the brain drains waste, and others to conclude that brain is an exceptional organ. Then in 2015, two studies of mice found evidence of the brain’s lymphatic system in the dura. Coincidentally, that year, Dr Reich saw a presentation by Jonathan Kipnis, Ph.D., a professor at the University of Virginia and an author of one the mouse studies.

“I was completely surprised. In medical school, we were taught that the brain has no lymphatic system,” said Dr Reich. “After Dr Kipnis’s talk, I thought, maybe we could find it in human brains?”

To look for the vessels, Dr Reich’s team used MRI to scan the brains of five healthy volunteers who had been injected with gadobutrol, a magnetic dye typically used to visualize brain blood vessels damaged by diseases, such as multiple sclerosis or cancer. The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood-brain barrier and enter other parts of the brain.

At first, when the researchers set the MRI to see blood vessels, the dura lit up brightly, and they could not see any signs of the lymphatic system. But, when they tuned the scanner differently, the blood vessels disappeared, and the researchers saw that dura also contained smaller but almost equally bright spots and lines which they suspected were lymph vessels. The results suggested that the dye leaked out of the blood vessels, flowed through the dura and into neighbouring lymphatic vessels.

To test this idea, the researchers performed another round of scans on two subjects after first injecting them with a second dye made up of larger molecules that leak much less out of blood vessels. In contrast with the first round of scans, the researchers saw blood vessels in the dura but no lymph vessels regardless of how they tuned the scanner, confirming their suspicions.

They also found evidence for blood and lymph vessels in the dura of autopsied human brain tissue. Moreover, their brain scans and autopsy studies of brains from nonhuman primates confirmed the results seen in humans, suggesting the lymphatic system is a common feature of mammalian brains.

“These results could fundamentally change the way we think about how the brain and immune system inter-relate,” said Walter J. Koroshetz, M.D., NINDS director.

Dr Reich’s team plans to investigate whether the lymphatic system works differently in patients who have multiple sclerosis or other neuroinflammatory disorders.

  • eLife: 10.7554/eLife.29738 di

Gene therapy shows promise for reversing blindness

In a laboratory study in Oxford, researchers have shown how it might be possible to reverse blindness using gene therapy to reprogram cells at the back of the eye to become light sensitive. Most causes of untreatable blindness occur due to loss of the millions of light sensitive photoreceptor cells that line the retina, similar to the pixels in a digital camera.

The remaining retinal nerve cells which are not light sensitive however remain in the eye. Samantha de Silva and colleagues used a viral vector to express a light sensitive protein, melanopsin, in the residual retinal cells in mice which were blind from retinitis pigmentosa, the most common cause of blindness in young people.

The mice were monitored for over a year and they maintained vision during this time, being able to recognise objects in their environment which indicated a high level of visual perception. The cells expressing melanopsin were able to respond to light and send visual signals to the brain. The Oxford team has also been trialling an electronic retina successfully in blind patients, but the genetic approach may have advantages in being simpler to administer.

The research was led by Professors Robert MacLaren and Mark Hankins at the Nuffield Laboratory of Ophthalmology in Oxford. Samantha de Silva, the lead author of the study said: “There are many blind patients in our clinics and the ability to give them some sight back with a relatively simple genetic procedure is very exciting. Our next step will be to start a clinical trial to assess this in patients.”

  • doi: 10.1073/pnas.1701589114

Typhoid vaccine proves highly immunogenic, could halve infection rate

A new typhoid vaccine has proven safe, highly immunogenic and could prevent more than half of typhoid infections according to a new study published in The Lancet. The study is a phase 2b trial of 112 adults and provides the first efficacy data for the leading candidate vaccine being considered for widespread use in children under 2 years, who are disproportionately affected by typhoid.

The trial uses a controlled human infection model, in which healthy volunteers are vaccinated and then deliberately exposed to the pathogen. These types of studies have been used to support the development of various vaccines (including the licenced cholera vaccine) as they can be rapidly deployed to assess vaccine efficacy.

The Vi-conjugate vaccine studied in this trial is only licensed for use in children under 2 years in India, and there are no typhoid vaccines licensed worldwide for use in children under 2 years old.

The study provides evidence to support the development of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever, and the authors say that phase 3/4 and cost-effectiveness studies are now needed. The WHO’s Strategic Advisory Group of Experts were due to consider the use of Vi-conjugate vaccines for the control of typhoid fever in October 2017, with subsequent decisions on financing being made by the Global Alliance for Vaccines and Immunisation.

Typhoid affects between 12.5 and 20.6 million people worldwide in regions withinadequate water quality and poor sanitation, particularly in south Asia and sub-Saharan Africa. 1 in 100 cases are deadly and approximately 3% of cases become chronic carriers.

Typhoid is caused by Salmonella enterica serovar Typhi (S. Typhi bacteria) and is usually treated with antibiotics, but antibiotic resistance is increasing. Children are particularly susceptible to typhoid, but no vaccine is licenced for worldwide use in children under 2 years, contributing to poor adoption of typhoid immunisation programmes.

Writing in a linked Comment, Nicholas A Feasey, Liverpool School of Tropical Medicine (UK) and Myron M Levine, University of Maryland (US) say: “Results of this volunteer challenge have been awaited with much anticipation by the public health community interested in control of typhoid fever in endemic areas of south Asia and sub-Saharan Africa where S Typhi is increasingly antibiotic resistant and few treatment options remain. Vi-conjugate vaccines that have been in development represent a new instrument to help to control typhoid.” They note that the most advanced conjugate vaccine, (Typbar- TCV) is licensed in India where it has been shown to elicit robust serum Vi-antibody responses in Indian infants as young as 6 months of age, and an application for pre-qualification has been submitted to WHO. They add: “If approved, this would allow the vaccine to be procured by UN agencies. However, despite evidence of safety and immunogenicity in Indian children and adults, heretofore, there has been no evidence of actual efficacy of the vaccine in diminishing the attack rate of typhoid fever upon exposure to virulent S Typhi compared with the control participants. Importantly, the authors provide the first data documenting that Typbar-TCV is protective.”


US NIH releases largest publicly available chest X-ray dataset to global scientific community

The NIH Clinical Center recently released over 100,000 anonymized chest x-ray images and their corresponding data to the scientific community. The release will allow researchers across the country and around the world to freely access the datasets and increase their ability to teach computers how to detect and diagnose disease. Ultimately, this artificial intelligence mechanism can lead to clinicians making better diagnostic decisions for patients.

NIH compiled the dataset of scans from more than 30,000 patients, including many with advanced lung disease. Patients at the NIH Clinical Center, the nation’s largest hospital devoted entirely to clinical research, are partners in research and voluntarily enrol to participate in clinical trials. With patient privacy being paramount, the dataset was rigorously screened to remove all personally identifiable information before release.

Reading and diagnosing chest x-ray images may be a relatively simple task for radiologists but, in fact, it is a complex reasoning problem which often requires careful observation and knowledge of anatomical principles, physiology and pathology. Such factors increase the difficulty of developing a consistent and automated technique for reading chest X-ray images while simultaneously considering all common thoracic diseases.

By using this free dataset, the hope is that academic and research institutions will be able to teach a computer to read and process extremely large amounts of scans, to confirm the results radiologists have found and potentially identify other findings that may have been overlooked.

In addition, this advanced computer technology may also be able to:

  • help identify slow changes occurring over the course of multiple chest x-rays that might otherwise be overlooked
  • benefit patients in developing countries that do not have access to radiologists to read their chest x-rays, and
  • create a virtual radiology resident that can later be taught to read more complex images like CT and MRI in the future.

With an ongoing commitment to data sharing, the NIH research hospital anticipates adding a large dataset of CT scans to be made available as well in the coming months.

Images are available via Box :https://nihcc.app.box.com/v/ChestXray-NIHCC

 

 

Date of upload: 22nd Nov 2017

                                  
                                                           Copyright © 2017 MiddleEastHealthMag.com. All Rights Reserved.