Positive Health Online

Survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumour suppressant

A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene - a gene that promotes the development of cancer - and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.

The study, which was published in Nature Communications, was led by Prof Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU's Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr Shay Eliyahu, both of Prof. Satchi-Fainaro's multidisciplinary laboratory, in collaboration with Prof Eytan Ruppin of TAU's Computer Science Department and the University of Maryland and Prof Iris Barshack and Dr Talia Golan of Chaim Sheba Medical Center, Tel Hashomer.

Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within just a year of diagnosis. "Despite all the treatments afforded by modern medicine, some 75% of all pancreatic cancer patients die within 12 months of diagnosis, including many who die within just a few months," Prof. Satchi-Fainaro says.

"But around seven percent of those diagnosed will survive more than five years. We sought to examine what distinguishes the survivors from the rest of the patients," Prof Satchi-Fainaro continues. "We thought that if we could understand how some people live several years with this most aggressive disease, we might be able to develop a new therapeutic strategy."

Calling a Nano-Taxi

The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumour suppressant, and PLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation made sense for such an aggressive cancer. But the team needed to see if the same was true in humans. The scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients. The molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer.

The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumour and prevents side effects in surrounding healthy tissues.

"We designed a nanocarrier  to deliver two passengers: (1) miR-34a, which degrades hundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), that silences a single gene," Prof. Satchi-Fainaro says. "These were delivered directly to the tumor site to change the molecular signature of the cancer cells, rendering the tumor dormant or eradicating it altogether.

"The nanoparticle is like a taxi carrying two important passengers," Prof Satchi-Fainaro continues. "Many oncology protocols are cocktails, but the drugs usually do not reach the tumor at the same time. But our 'taxi' kept the 'passengers' - and the rest of the body - safe the whole way, targeting only the tumor tissue. Once it 'parked,' an enzyme present in pancreatic cancer caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address — the tumor cells."

Improving the Odds

To validate their findings, the scientists injected the novel nanoparticles into pancreatic tumour-bearing mice and observed that by balancing these two targets - bringing them to a normal level by increasing their expression or blocking the gene responsible for their expression - they significantly prolonged the survival of the mice.

"This treatment takes into account the entire genomic pattern, and shows that affecting a single gene is not enough for the treatment of pancreatic cancer or any cancer type in general," according to Prof. Satchi-Fainaro.

Research for the study was funded by the European Research Council (ERC), Tel Aviv University's Cancer Biology Research Center (CBRC) and the Israel Science Foundation (ISF).

Further Information

Source: George Hunka <ghunka@aftau.org>

Contact: Jordan Isenstadt Marino  <jisenstadt@marinopr.com>
Tel: +1 212.402.3510
https://www.aftau.org/weblog-medicine--health?=&storyid4704=2370&ncs4704=3&erid=6947555

16 Week NHS Programme can help Treat Type 2 Diabetes

An inexpensive, 16-week NHS lifestyle programme aimed at patients with type 2 diabetes can help to treat the disease. A new study led by the University of Glasgow and published today in Diabetes Obesity and Metabolism,[1] showed how effective the NHS Greater Glasgow and Clyde Glasgow and Clyde Weight Management Service lifestyle programme was at reducing the need for diabetic medication or insulin over a three year period.

Researchers found that patients who successfully completed the programme had no increase in their oral diabetes medication, and were half as likely to progress to insulin as those who didn’t complete the programme and those who did not lose weight. As type 2 diabetes is a progressive condition, patients who were not referred, or did not successfully complete the programme, required increased amounts of oral diabetes medications over the subsequent 3 years. The study also found that patients who successfully completed the programme went on to maintain that greater weight loss over a three year period, than either those who didn’t complete the programme or those not referred to it.

In light of the findings researchers believe that this kind of lifestyle programme may be even more effective than some pharmacological alternatives in treating type 2 diabetes.

The study examined records from the NHS 16-week lifestyle programme, which included a regime of diet, exercise and behaviour change. The programme consists of nine fortnightly classes. Researchers defined ‘success’ as losing 5kg in that nine week timeframe. Patients could then choose to stay on for further weight loss and maintenance classes (1 per month) over the next year. Patients with Type 2 diabetes had to have a body mass index of 30 or above, in order to qualify to be referred to the programme. To judge whether the programme was a success, researchers compared the successful group against those who attended and didn't lose weight, or those who didn't complete, or those who were never referred.

Dr Jennifer Logue, lead author of the study from the University of Glasgow, said: “This is the first real-world study to show that the lifestyle weight management programmes that we deliver in the NHS can have a long lasting meaningful clinical effect on type 2 diabetes.

“This study shows that the common assumption that the weight lost is quickly regained is not true. Currently weight management programmes in the NHS are under-resourced and there is a lack of belief in their effectiveness by clinicians leading to low levels of referral, despite them being recommended by NICE.

“Our hope is that this study will convince patients, clinicians and NHS managers that these inexpensive programmes can make a clinically significant difference to patients with type 2 diabetes.”

The researchers believe these kinds of programmes need to be better resourced so that more patients can achieve the defined ‘success’ weight loss of 5kg. Currently, only a minority of those who attended the programme achieved the 5kg weight loss. However researchers believe that this number would go up in line with investment to address the accessibility of programmes, so that people are able to attend regularly while continuing with work and caring commitments.

The study, ‘The effect of non-surgical weight management on weight and glycaemic control in people with type 2 diabetes: a comparison of interventional and non-interventional outcomes at three years’ is published in Diabetes Obesity and Metabolism.[1]

Reference

1. Botha, S., Forde, L., MacNaughton, S., Shearer, R., Lindsay, R., Sattar, N., Morrison, D., Welsh, P. and Logue, J. (2017) The effect of non-surgical weight management on weight and glycaemic control in people with type 2 diabetes: a comparison of interventional and non-interventional outcomes at three years. Diabetes, Obesity and Metabolism, (doi:10.1111/dom.13171) (PMID:29178635) (Early Online Publication)

Source and Further Information

Source: Elizabeth McMeekin <Elizabeth.mcmeekin@glasgow.ac.uk>

For more information contact Elizabeth McMeekin Elizabeth.mcmeekin@glasgow.ac.uk or Ali Howard ali.howard@glasgow.ac.uk in the University of Glasgow Communications and Public Affairs Office on Tel: 0141 330 4831 / 0141 330 6557.

New Wholegrain Labelling System helps Consumers Choose Healthy Breakfast Options

University of Hertfordshire researchers have been trailing a new approach to help the public easily identify which wholegrain foods are healthiest. Currently there is no national or international definition of what a wholegrain food is, leading to some foods containing high levels of fat or sugar being labelled as wholegrain, particularly breakfast cereals, and appearing to be healthier than they are. Their findings have been published in the online journal Public Health Nutrition[1] and could be used by food manufacturers to develop a new food labelling system in addition to the current traffic light system.

The UK Institute of Grocery Distribution recommend that a food should have at least 8g of wholegrain ingredients per serving to be called whole grain. However, this recommendation is non-binding and the content of other nutrients are not specified in relation to this resulting in some foods, currently described as wholegrain, also having high levels of sugar or fat.

Researchers Bahar Ghodsian and Angela Madden have found that wholegrain foods with a carbohydrate: fibre ratio of less than 10:1 tend to be the lowest in fat, sugar and salt.  A total of 266 breakfast cereals and 162 breads sold at the four major UK supermarkets were identified as meeting this criterion and their nutritional quality was compared with the Food Standards Agency traffic light system. Breads which met the criterion typically contained medium fat, low saturated fat, low sugar and medium salt whilst breakfast cereals typically contained medium fat, low saturated fat, high sugar and low salt.

The benefits associated with eating wholegrain ingredients are well-established and include reducing the risk of cardiovascular disease (CVD), type 2 diabetes and many cancers. However, wholegrain intake in the UK remains low with 45% of the population eating less than one serving per day and 18% eating none over a four-day period. 

Dr Angela Madden, Lead for Nutrition and Dietetics at the University of Hertfordshire who supervised the project, said “In the UK, the average intake of sugar is higher than recommended and average intake of fibre is less than recommended. There is lots of information in the media about sugar but people often forget about fibre and it is important to consider both of these, especially in foods like breads and cereals.

“A public health initiative is clearly needed to substitute foods containing whole grains for those containing significant amounts of refined grains in order to improve health, save resources and reduce mortality.

“Our work shows that using the carbohydrate:fibre ratio helps to identify foods that have good nutritional value. It supplements the existing front-of-pack traffic light labelling currently in use. We suggest that food manufacturers should consider adopting this approach to help consumers.”

Reference

1. Bahar Ghodsian (a1) (a2) and Angela M Madden (a1). Evaluating the ≤10:1 wholegrain criterion in identifying nutrient quality and health implications of UK breads and breakfast cereals. Public Health Nutrition. 26 Dec 2017. https://doi.org/10.1017/S1368980017003718

Further Information

For more information/images contact the University of Hertfordshire Press Office news@herts.ac.uk on Tel: 01707 285770;

The lead researchers have written a blog explaining the study in more details which is available here: http://blog.journals.cambridge.org/category/medicine-health-science/nutrition/  

The academic paper, published online in the journal Public Health Nutrition can be found here: https://www.cambridge.org/core/journals/public-health-nutrition/article/evaluating-the-101-wholegrain-criterion-in-identifying-nutrient-quality-and-health-implications-of-uk-breads-and-breakfast-cereals/4E7B1A35054C404A614EBCFE214C6063