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Liquid Biopsies gain Traction for Cancer Diagnosis


In search of a simple, non-invasive and economically feasible way of diagnosing cancer, an approach adopted by the Weizmann Institute of Science may lead to a blood test that will diagnose cancer with unprecedented accuracy.


“Many of the conventional methods clinically available today to detect and diagnose cancer are invasive and unpleasant,” explains research lead Dr. Efrat Shema of Weizmann’s Immunology and Regenerative Biology Department. “Eliminating the discomfort means that people would be less likely to avoid getting tested – and more likely to have their cancers detected earlier,” said Vadim Fedyuk, who led the study together with fellow graduate student Nir Erez.


The idea behind using liquid biopsies arose from the fact that blood contains free-fl oating DNA and proteins shed by dead blood cells in healthy people – and in cancer patients, by dead tumor cells as well. “Some of the byproducts of cell destruction, including cancer DNA and proteins, are dumped into the bloodstream and we know how to collect and analyse them,” Shema said.


Her approach to development of a test to assess multiple epigenetic parameters, builds on a method for imaging individual molecules that she had developed during her postdoctoral research at Harvard Medical School and the Broad Institute. The method makes it possible to achieve accurate epigenetic mapping with only a very small amount of raw material, using a fl uorescent microscope. It can be employed, for example, to view epigenetic markings on nucleosomes, pieces of DNA wrapped around protein ‘spools’. These may be shed into the bloodstream like bits of fl otsam when cells are destroyed, so Shema reasoned that the millions of nucleosomes found in the blood could be analysed to detect cancer.


Using Shema’s single-molecule imaging method, Fedyuk and Erez, together with colleagues, compared the nucleosomes in the blood of 30 healthy individuals with those of 60 patients with different stages of


colorectal cancer. They found that the nucleosomes of the two groups were characterised by vastly different patterns of epigenetic marking. This analysis covered six different epigenetic modifi cations linked to cancer, as well as a variety of other cancer indicators, including protein segments from dead tumors, which are undetectable by conventional technologies.


Next, in collaboration with Professor Guy Ron from the Racah Institute of Physics at the Hebrew University of Jerusalem, the scientists combined what they had revealed about the molecular biology of cancer with artifi cial intelligence algorithms, applying machine learning to the large data sets obtained from the two groups. The scientists also applied their technology to compare blood nucleosomes of healthy volunteers with those of 10 patients with pancreatic cancer.


“Our algorithm could tell the difference between the healthy and the patient groups at a record level of certainty for studies of this type – with 92% precision,” Shema said. The scientists call the new technology EPINUC, an acronym for “epigenetics of plasma-isolated nucleosomes.”


If supported by studies involving a greater number of patients, these fi ndings could lead to a multiparameter blood test for detecting and diagnosing cancer using less than 1 ml of blood. In the future, because of the level of detail revealed in the analysis, the results of this blood test might also advance personalised medicine by suggesting the best treatments for each individual patient.


Shema summed up: “We’ve achieved a successful proof of concept for our method, which now needs to be confi rmed in clinical trials. In the future, our multiparameter approach may serve to diagnose not only various cancers but also additional diseases that leave traces in the blood, such as autoimmune disorders or heart disease.”


Dr Efrat Shema’s research is supported by the Swiss Society Institute for Cancer Prevention Research and the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics.


Pictured (l-r) Nir Erez, Dr. Noa Furth, Dr. Efrat Shema and Vadim Fedyuk


Different patterns of epigenetic markers revealed by EPINUC on blood nucleosomes (bright-red dots) of a healthy person (left) and a colorectal cancer patient (right)


Dr Shema is the incumbent of the Lisa and Jeff Aronin Family Career Development Chair.


The research was published in Nature Biotechnology. More information online: ilmt.co/PL/O2Qm


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Feathered Friends Scoop Top Prizes in Royal Society of Biology Photography Competition


The Royal Society of Biology has announced the winners of this year’s Photography Competition, with two amateur photographers named as Photographer and Young Photographer of the Year. The competition invites amateur photographers aged 18 and over to submit photographs based around a particular theme, for a chance to win £1000. The Young Photographer of the Year competition is open to those under the age of 18, and offers a prize of £500.


The theme of this year’s competition was ‘Communication’, which saw entries capturing the sharing of information within and between different species, such as in the colouration of feathers, fl owers and fur, as well as courtship behaviour and territorial displays.


The winning entry for Young Photographer of the Year, taken by 11-year- old George Lanstone-Futcher from Kent, depicts two Puffi ns billing on Skomer. Puffi ns mate for life and billing is a part of their mating and courtship ritual. They often live for over 30 years so this communication is an essential part of their journey to being connected for life.


Commenting on his recent win, George said: “I am so grateful to the RSB for choosing my photograph as the winning entry, I’m very surprised and happy to have been chosen. I was lucky to spend 3 days on Skomer Island and inspiration was everywhere, but Puffi ns are the best, as everyone knows!”


The winner for the Photographer of the Year is Agnieszka Florczyk, who took a photo of two Red-necked Grebe’s during mating season in Poland. The photo was taken at dawn on an overgrown pond in the Barycz valley, where grebes communicate vividly with each other by tooting, dancing and offering gifts in the form of aquatic plants.


“I am very excited and grateful that the judges noticed my picture,” says Agnieszka, “this spectacle with the Red-necked Grebes is always something special, the birds are fully focussed on each other. In this picture, we can see the close relationship between the birds and I’m very glad I was able to capture this exact moment. The most important aspect for me is the contact with natures itself.”


The winners of the competition were announced at the RSB Annual Awards Ceremony on 6th October at Carlton House Terrace, as part of this year’s Biology Week.


The competition was judged by: Alice Campain, CABI; Tim Harris, Nature Picture Library and Bluegreen Pictures; Tom Hartman, The University of Nottingham; Alex Hyde, natural history photographer and Linda Pitkin, underwater photographer.


More information online: ilmt.co/PL/E25j 58905pr@reply-direct.com


RUNNER-UP Photographer of the Year : Morning call - Adrian Soldati Location: Budongo, Uganda Caption: Adrian captured this image of the alpha male of a wild chimpanzee community who is producing a long distance vocalisation early in the morning to coordinate movements with the other group members that are scattered in the forest and out-of-sight. Equipment: I used a Nikon D500 camera with a Tamron SP 70-200 2.8 IS lens. The settings I used were 1/400 of a second, aperture f 2.8, ISO 5000, and 165 mm. I took the photograph in the Budongo Forest, in Uganda.


RUNNER-UP Young Photographer of the Year: Sun-bathed Brahminy - Anushree Parihar Location: Hadwani, Uttarkhand, India Caption: Anushree took this photo in India of this couple of Brahminy starlings enjoying the first rays of sun and communicating with one another. Equipment: NIKON CORPORATION COOLPIX P950 F6.5 1/250 s 357.00mm ISO 180 White Balance Auto No flash


Young photographer of the Year: Puffins billing on Skomer - George Lanstone-Futcher Location: Skomer, Wales, UK Caption: George snapped this photo of these two Puffins, captured in the early evening on The Wick on Skomer Island. They are engaged in Billing, a part of their mating and courtship ritual. Equipment: Canon EOS 2000D Camera with Canon EF 600mm f/4L IS II USM Lens. ISO 200, f7.1, 1/10


WINNER Photographer of the Year: Talks at dawn - Agnieszka Florczyk. Location: Barycz Valley, Poland Caption: Agnieszka took this photo at dawn on an overgrown pond in the Barycz valley, where grebes communicate vividly with each other by tooting, dancing and offering gifts in the form of aquatic plants. Equipment: Nikon D5 Nikkor f/2,8 400mm + TC 1,7 iso 2000 1/2500s f/4,8 680mm


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