Positive Health Online

Stopping Breast Cancer Metastasis in Its Tracks 

TAU researcher harnesses targeted delivery of microRNAs to primary tumours in mice to block the movement of cancer

A new Tel Aviv University study finds that combining genetic therapy with chemotherapy delivered to a primary tumor site is extremely effective in preventing breast cancer metastasis.

The research was led by Dr Noam Shomron of TAU's Sackler School of Medicine in collaboration with Dr Natalie Artzi of the Massachusetts Institute of Technology, and conducted by Dr Shomron's students Avital Gilam and Dr Daphna Weissglas and Dr Artzi's student Dr Joao Conde. Data on human genetics were provided by Prof. Eitan Friedman of TAU's Sackler Faculty of Medicine and Chaim Sheba Medical Center.

The research was published in the September 19, 2016, online issue of Nature Communications.[1]

Stopping Cancer at the Turning Point

One in eight women worldwide are diagnosed with breast cancer during their lifetimes. Breast cancer is the second leading cause of cancer death in women. The chance that a woman will die from breast cancer is about 1 in 36. Early detection, while increasingly common, is not sufficient to preventing metastasis, the lethal movement of cancerous cells from a primary tumor site to colonies in vital organs. About 80 percent of women with metastatic cancer die from the disease within just five years of being diagnosed.

"The situation is bleak. Death rates from breast cancer remain high and relatively unchanged despite advances in medicine and technology," said Dr Shomron. "We wanted to find a way to stop metastasis from happening altogether. It's the turning point, where survival rates drop exponentially.

"Our mission was to block a cancer cell's ability to change shape and move. Cancer cells alter their cytoskeleton structure in order to squeeze past other cells, enter blood vessels and ride along to their next stop: the lungs, the brain or other vital organs. We chose microRNAs as our naturally-occurring therapy, because they are master regulators of gene expression."

Database, Drugs and Delivery

The researchers based their approach on the ‘3Ds’ - database, drugs and delivery. The team began by exploring bioinformatics databases to investigate the span of mutations in a tumour and identify precisely which ones to target. The scientists then procured a naturally-occurring, RNA-based drug to control cell movement and created a safe nanovehicle with which to deliver the microRNA to the tumour site.

"We looked at mutations and polymorphisms that other researchers have ignored," said Dr Shomron. "Mutations in the three prime untranslated regions (UTRs) at the tail end of a gene are usually ignored because they aren't situated within the coding region of the gene. We looked at the three UTR sites that play regulatory roles and noticed that mutations there were involved in metastasis."

Two weeks after initiating cancer in the breasts of their mouse ‘patients’, the researchers injected into primary tumour sites a hydrogel that contained naturally occurring RNAs to target the movement of cancer cells from primary to secondary sites. Two days after this treatment, the primary breast tumours were excised.

The mice were evaluated three weeks later using CT imaging, fluorescent labelling, biopsies and pathology. The researchers discovered that the mice that had been treated with two different microRNAs had very few or no metastatic sites, whereas the control group - injected with random scrambled RNAs - exhibited a fatal proliferation of metastatic sites.

From Mice to Humans

"We realized we had stopped breast cancer metastasis in a mouse model, and that these results might be applicable to humans," said Dr Shomron. "There is a strong correlation between the effect on the genes in mouse cells and the effect on the genes in human cells. Our results are especially encouraging because they have been repeated several times at TAU and at MIT by independent groups."

The researchers are continuing their study of the effects of microRNAs on tumours within different microenvironments.

References

1. Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Natalie Artzi, Noam Shomron. Local microRNA delivery targets Palladin and prevents metastatic breast cancer. Nature Communications, 2016; 7: 12868 DOI: 10.1038/ncomms12868    www.nature.com/ncomms/2016/160919/ncomms12868/full/ncomms12868.htm

Further Information

Watch Prof. Shomron’s TEDx talk about his research: www.youtube.com/watch?v=wAoZym_anr0

Source: "George Hunka, American Friends of Tel Aviv University" <ghunka@aftau.org>

Republished from aftau.org

Nearly One-Third of Unnecessary Endoscopies could be Avoided with Faeces Blood Test

The number of patients referred to the hospital for an unnecessary endoscopy could be cut by nearly a third if an additional test that can be carried out by a GP could be incorporated, according to new research published in the open access journal BMC Medicine.[1]

This new diagnostic strategy for patients suspected of serious colorectal disease (SCD) was developed by researchers based at hospitals across the Netherlands. Their study showed that SCD can be more accurately excluded at the GP’s clinic if the doctor carries out an additional test, and so reduce the number of people requiring an invasive endoscopy.

Serious colorectal diseases, including colorectal cancer, are difficult to diagnose as the signs and symptoms are not always clear. Any suspicion of SCD requires a GP referral to a hospital for an endoscopy but studies have shown that between 60-80% of referred patients end up not having SCD.

Dr Sjoerd Elias, corresponding author from the Julius Centre for Health Sciences and Primary Care at the University Medical Center in Utrecht, said: “The amount of patients that are unnecessarily referred for an endoscopy strains health care budgets and exposes patients to a small but realistic risk from endoscopy associated complications. Our study found that using a test called FIT, which detects the presence of haemoglobin in the patient’s faeces, alongside the usual diagnostic work up done by GPs could rule out nearly a third of patients from requiring an endoscopy to check for SCD.”

The research uses data collected from the large-scale CEDAR study where 810 patients suspected of SCD were enrolled from 266 primary care practices in the Netherlands. All the patients were subjected to FIT before being referred for an endoscopy. FIT is a well-established test that is already used as a basis for colorectal cancer screening. The test uses an antibody that recognizes human haemoglobin and so can be used to detect the presence of blood in a patients stool sample.

Out of the 810 patients referred for an endoscopy, 669 were found to have no SCD. Once the results of the FIT test had been taken into account the researchers found that approximately 30% of these patients could have been prevented from having an endoscopy as they may have been correctly diagnosed as not having SCD during their GP visit.

The study also looked at the benefit of adding a faecal test for the protein calprotectin to the diagnostic strategy. They found that this test also improved the diagnosis of SCD but not to the same extent as FIT. Furthermore, combining both tests added little extra benefit to the diagnostic accuracy of FIT alone.

The authors note that while the addition of FIT could be able to substantially reduce the number of unnecessary endoscopy referrals, there is still a small risk that some patients with SCD will be misdiagnosed and not referred for the procedure. In this study, one patient with colorectal cancer would not have been selected for endoscopy referral. However, the authors say that in such cases careful monitoring for persistent symptoms would delay rather than miss the diagnosis.

References 

1. Sjoerd G. Elias, Liselotte Kok, Niek J. de Wit, Ben J. M Witteman, Jelle G. Goedhard, Mariëlle J. L. Romberg-Camps, Jean W. M. Muris and Karel G. M. Moons. Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study. BMC Medicine 2016 DOI: 10.1186/s12916-016-0684-5.

The article is available at the journal website: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0684-5

Further Information

BioMed Central is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Nature, a major new force in scientific, scholarly, professional and educational publishing, created in May 2015 through the combination of Nature Publishing Group, Palgrave Macmillan, Macmillan Education and Springer Science+Business Media. www.biomedcentral.com

Source

"Lam, Matthew, BioMed Central Ltd." matthew.lam@biomedcentral.com

Sleeping Sickness: Parasites Found Hiding in the Skin

Source: pasteur.fr

Scientists from the Trypanosome Cell Biology Unit (Institut Pasteur/Inserm), working in collaboration with scientists from the University of Glasgow, have demonstrated the presence of a large quantity of trypanosomes - the parasites responsible for sleeping sickness - in the skin of individuals with no symptoms. This discovery should refocus the screening strategy for this disease, which was previously based on the detection of parasites in the bloodstream, and raises the possibility of eliminating the disease in West Africa. The scientists' results were published in e-Life on September 22, 2016.[1]

Left: Trypanosomes (Trypanosoma brucei brucei, fluorescent green) in the dermis of a mouse with no parasites in the bloodstream, 29 days after infection. © Institut Pasteur

Right: A trypanosome (Trypanosoma brucei gambiense, the purple cell indicated by a black arrow) in the dermis of an asymptomatic individual living in an endemic area in the Democratic Republic of Congo. © Institut Pasteur

Sleeping sickness affects between 4,000 and 8,000 people in Sub-Saharan Africa each year. The disease can be fatal if the parasites reach the central nervous system. "In recent centuries, sleeping sickness has almost been eradicated in West Africa on two occasions," explained Brice Rotureau, head of the Trypanosome Transmission Group in the Trypanosome Cell Biology Unit (Institut Pasteur/Inserm). "But each time the disease has reappeared, with many infected individuals seemingly slipping through the net during screening campaigns and continuing to transmit the parasite Trypanosoma brucei gambiense - [the parasite responsible for more than 98% of reported cases] - to its insect vector, the tsetse fly." It is thought that in at least 30% of cases, the serological screening test is positive, despite no living parasites being detected in the bloodstream. But if the parasites are not in the blood, where are they hiding? Here is the question that scientists from the Institut Pasteur, the University of Glasgow, the University of Kinshasa and the French Research Institute for Development (IRD) set out to investigate.

In this study, scientists from the Institut Pasteur decided to monitor the evolution and distribution of Trypanosoma brucei parasites in real time in mouse models. Trypanosomes that had been modified to emit both fluorescence and bioluminescence were transmitted to these mice via tsetse flies, their natural vectors. "We saw a huge number of parasites in the skin, a much larger quantity than in the bloodstream," described Brice Rotureau. "And at tissue level, we observed trypanosomes at the base of the dermis moving in the inter-cellular matrix, outside the vascular system. The parasites were distributed very evenly, as if they were trying to optimize their chances of being taken up by a tsetse fly so that they could be transmitted to a new host."

The scientists' research enabled them to prove that trypanosomes were hiding in the skin. But in order to provide conclusive evidence that the trypanosomes could be absorbed by flies when they feed on mice, they then exposed infected mice to naive tsetse flies - [without parasites]. These mice had parasites in their skin but not in their bloodstream. The scientists' experiments revealed that when the flies fed on areas of the skin with no parasites, they were not infected. But the flies that fed on parts of the skin with a high density of parasites were infected. In other words, parasites in the skin can be transmitted to tsetse flies and can therefore result in new cases of sleeping sickness.

The study also demonstrated the presence of trypanosomes in the skin of African patients, including individuals who had received a negative diagnosis for the disease. These patients were actually healthy carriers who served as reservoirs for the parasite Trypanosoma brucei gambiense and who should have been treated. All these findings offer new hope for the treatment of sleeping sickness.

The scientists are now working on rapid and non-invasive screening procedures which would reveal any trypanosomes hidden in the skin and identify healthy carriers that have not been identified by previous screening tests. "Now that we know where to look, we can seriously think about eradicating sleeping sickness in West Africa in the relatively near future – especially since the epidemiological situation, with cases at a record low, is ripe for action," explained Brice Rotureau. "We hope that our work will provide a valuable tool that enables WHO to launch an eradication campaign on all fronts, involving screening, treatment of patients and healthy carriers, and vector control measures."

Reference

1. Paul Capewell^1*, Christelle Cren-Travaillé^2*, Francesco Marchesi³, Pamela Johnston³, Caroline Clucas¹, Robert A Benson⁴, Taylor-Anne Gorman^1,4, Estefania Calvo-Alvarez², Aline Crouzols², Grégory Jouvion⁵, Vincent Jammoneau⁶, William Weir¹, M Lynn Stevenson³, Kerry O’Neill¹, Anneli Cooper¹, Nono-raymond Kuispond Swar⁷, Bruno Bucheton⁶, Dieudonné Mumba Ngoyi⁸, Paul Garside⁴, Brice Rotureau^2** and Annette MacLeod^1** The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes, e-Life, September 22, 2016. http://dx.doi.org/10.7554/eLife.17716   https://elifesciences.org/content/5/e17716

¹ Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Henry Wellcome Building for Comparative Medical Sciences, Garscube Estate, Glasgow, United Kingdom, G61 1QH

² Trypanosome Transmission Group. Trypanosome Cell Biology Unit, INSERM U1201 & Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France

³ Veterinary Diagnostic Services, Veterinary School, University of Glasgow, Garscube Estate, Glasgow, United Kingdom, G61 1QH

⁴ Institute of Infection, Immunology and Inflammation, College of Medical, Veterinary and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom, G12 8TA

⁵ Human Histopathology and Animal Models Unit, Institut Pasteur, Paris, France

⁶ Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177, Campus International de Baillarguet, Montpellier, France

⁷ University of Kinshasa, Kinshasa, Democratic Republic of the Congo

⁸ Department of Parasitology, National Institute of Biomedical Research (INRB), Kinshasa, Democratic Republic of the Congo

* Co-first authors

** Co-last authors

Republished from Press Release

www.pasteur.fr/en/institut-pasteur/press/press-documents/sleeping-sickness-parasites-found-hiding-skin

Published Research

http://dx.doi.org/10.7554/eLife.17716   https://elifesciences.org/content/5/e17716

Obesity - Dilemmas and Options

by Dr Edwin Alan Salter

A health authority recently proposed to restrict the availability of treatment to obese patients.  The plan was rescinded when a sharp backlash developed.  What can we learn from the controversy?

The directed and public declaration made it an inviting target for accusations of inequality and lack of sympathy.  But various factors besides limited resources may result in particular treatments not being offered to individuals, and this general caution clearly applies to those obese who, for example, run more risk in surgery and are less likely to gain fully from load bearing implants.  Perhaps also relevant to the opposition is a disapproval of criticising appearance.  Obesity, though  not a given like skin or facial structure, is an uncalculated achievement, so blaming is useless and sadness at self-harm is to be overcome positively.

Obesity (exceptions such as side-effects of illness or drugs apart) is a consequence of eating more than is balanced by activity.  Over-eating is indeed promoted in many ways: by the commerce of products both taste persuading (sugar, fat, salt …) and highly advertised for ease and appeal; poor education in simple cookery; our biology inherited from evolutionary circumstances of uncertain supply; a general culture of indulgence with consumption as a status sign (e.g. the image  of being served, of deserving high energy drinks); and the easy use of intake to reduce anxiety and substitute for positive quality of life (as lazy, harmful parenting inflicts).  These contemporary factors most bear on the already less privileged.

The cure is to eat less and to rebalance activity.  A measure of truth in the excuses “It's my genes, my fat cells ...” may guide cognitive help but in no way refutes intake reduction.  Passive devices flourish but have obvious costs and disadvantages.  Stomach surgery merely imposes permanent restriction that leaves  underlying predispositions unchanged.  The slimming industry implies that without its products (mostly stuff to consume) the task is too difficult.

I believe it is unhelpful for us to accept the notion of so-hard-to-cure addiction, that the damage to individuals and their families (whom they influence) and the burden of unfitness on society are too great.  Confidence and ego strength can be built in many ways, and numerous behavioural ploys are available to facilitate adjustment (from the general encouragement of making changes to the specificity of  small plates and a bun-free home).  Reduce sugar and your taste will adjust, don't eat for just one day and boast a little.

On any robust view, the management of eating is less than many of life's challenges and brings well-being with simplicity and cost-saving.  In the end, to put or not put the harmful into one's mouth is a voluntary act, a decision from which flow foreseeable consequences about future life.

Dr Edwin Alan Salter  <kl.humanfactors@talktalk.net>

Decision by MHRA to Ban Sale of Cannabidiol (CBD) Based Products

The comment below is from Professor Mike Barnes, a leading neurologist and co-author of the recent All-Party Parliamentary report on medical cannabis.  It is in response to the letter (issued 04-October 2016) from the MRHA to all UK suppliers of CBD products, telling them to cease trading within 28 days.

"I am surprised by this confused decision. If the MRHA and the UK government now consider that cannabis-derived CBD is a medicine, this is incompatible with the continuing Schedule 1 status of cannabis under the Misuse of Drugs Act that clearly states that cannabis has no medicinal value.  The decision by the MRHA to treat CBD products as medicines has also been done without thought to the consequences for many thousands of people in the UK who currently benefit from the products. It will have very significant and in many cases terminal impact on the many legitimate businesses that provide high quality products. The government must now act to sort out their muddled thinking and try to help those people with long term and often painful conditions who benefit from the ready and hitherto legal availability of natural cannabis products.  It is ironic that in acknowledging the therapeutic benefits of CBD, the MRHA is effectively suspending access to a product that has enhanced the lives of thousands for many years".

Professor Mike Barnes MB ChB MRCP(UK) FRCP MD

Mike Barnes MB ChB MRCP(UK) FRCP MD is a Professor of Neurological Rehabilitation and a trained consultant Neurologist and Rehabilitation Physician. During his career Mike has held positions within many organisations. He has been a Chief Executive within the NHS as well holding senior academic posts, mainly at the University of Newcastle. He founded the International Centre for Neurorehabilitation at Walkergate Park in Newcastle upon Tyne. He was the Founding President of the World Federation of NeuroRehabilitation and remains on the Executive Board. He has also been President of the British Society of Rehabilitation Medicine and is currently chair of the United Kingdom Acquired Brain Injury Forum (UKABIF). He may be contacted via www.profmichaelbarnes.co.uk .

Further Information

www.clear-uk.org/fast-developing-news-cbd-medicinal-cannabis/

www.clear-uk.org/professor-mike-barnes-speaks-out-on-the-cbd-ban/

http://volteface.me/cbd-ban-industry-responds/ 

Source

James Horne Associate Director Houston PR  <jhorne@houstonpr.co.uk>