Red onions pack a cancer-fighting punch, study reveals

The next time you walk down the produce aisle of your grocery store, you may want to reach for red onions if you are looking to fight off cancer. In the first study to examine how effective Ontario-grown onions are at killing cancer cells, University of Guelph researchers have found that not all onions are created equal.

Engineering professor Suresh Neethirajan and PhD student Abdulmonem Murayyan tested five onion types grown in Ontario and discovered the Ruby Ring onion variety came out on top. Onions as a superfood are still not well known. But they contain one of the highest concentrations of quercetin, a type of flavonoid, and Ontario onions boasts particularly high levels of the compound compared to some parts of the world.

The Guelph study revealed that the red onion not only has high levels of quercetin, but also high amounts of anthocyanin, which enriches the scavenging properties of quercetin molecules, said Murayyan, study’s lead author.

Anthocyanin is instrumental in providing colour to fruits and vegetables so it makes sense that the red onions, which are darkest in colour, would have the most cancer-fighting power.

Published recently in Food Research International, the study involved placing colon cancer cells in direct contact with quercetin extracted from the five different onion varieties.

We found onions are excellent at killing cancer cells,” said Murayyan. “Onions activate pathways that encourage cancer cells to undergo cell death. They promote an unfavourable environment for cancer cells and they disrupt communication between cancer cells, which inhibits growth.”

The researchers have also recently determined onions are effective at killing breast cancer cells. “The next step will be to test the vegetable’s cancer-fighting powers in human trials,” said Murayyan.

These findings follow a recent study by the researchers on new extraction technique that eliminates the use of chemicals, making the quercetin found in onions more suitable for consumption. Other extraction methods use solvents that can leave a toxic residue which is then ingested in food, said Neethirajan.

This new method that we tested to be effective only uses super-heated water in a pressurized container,” he said. “Developing a chemical-free extraction method is important because it means we can use onion’s cancer-fighting properties in nutraceuticals and in pill form.”

While we can currently include this superfood in salads and on burgers as a preventative measure, the researchers expect onion extract will eventually be added to food products such as juice or baked goods and be sold in pill form as a type of natural cancer treatment.

Murayyan et al. Antiproliferative activity of Ontario grown onions against colorectal adenocarcinoma cells. Food Res Int. 2017;96:12-18. doi: 10.1016/j.foodres.2017.03.017 [Abstract]

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The dark side of ‘junk’ DNA

The stretches of DNA between genes, littered with repeating sequences, were once considered the “junk of the genome,” but scientists are learning that some of this junk is far from harmless clutter. Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center report in the journal Cell Reports that certain short, repetitive sequences of DNA, or “junk,” play an important role in the development of Ewing sarcoma, a rare bone and soft tissue cancer that occurs most commonly in children and adolescents.

Some people may still think of these non-coding sequences as junk; that they don’t really do anything but act as hangers-on to the more famous parts of the genome,” said the study’s senior author Ian J. Davis, MD, PHD, a pediatric oncologist and researcher at UNC Lineberger and the Denman Hammond Associate Professor in Childhood Cancer at the UNC School of Medicine. “But we found that repetitive elements contribute to cancer development for Ewing sarcoma based on traits that they share with immature cells.”

For most people with Ewing sarcoma, the tumors have a mutation that creates a new gene called EWSR1-FLI1. This gene codes for a mutant protein, called an oncoprotein, that drives the cancer. But it turns out that the mutant protein does not work alone.

UNC Lineberger researchers found that specific states of DNA have enhanced susceptibility to the oncoprotein’s attack. In particular, the way that repetitive DNA sequences interact with a class of proteins called histones, which act like a spool around which DNA is wrapped, offer an opportunistic environment for the oncoprotein. At certain sites, the DNA is more “open” or unwrapped around the histone spools, making them more accessible to the oncoprotein.

Davis and his collaborators discovered that the way certain repeat DNA sections interact with histones in Ewing sarcoma bore a striking similarity to that of stem cells, which are cells that haven’t matured and can still become many types of cells. They believe that the looseness in the way that DNA and histones interact in stem cells and cancer cells at these repeat sites allows the oncoprotein to interact with the DNA, changing the way that many genes are expressed.

We identified a new feature in the way the genome is organized in stem cells, and this ended up explaining a link between these immature cells and the development of Ewing sarcoma,” Davis said. “This is one way we think the oncogene capitalizes on a pre-existing environment and offers some insight into why the cancer might have a very specific window during which it could develop. It’s kind of like a seed and soil relationship. The oncoprotein ‘seed’ can only form cancer in the correct stem cell ‘soil.’

The finding builds on previous research by Davis and others that showed the oncoprotein travels to certain non-coding, repeating sequences of DNA – repeating sections that have been a source of scientific and evolutionary debate, and at one time, were called “junk.” At those sites, the oncoprotein helps to keep the DNA at those sites “open,” allowing for nearby genes to be read and used as a blueprint for protein construction. Many genes implicated in tumor development are located near those repeat DNA sites.

While the oncoprotein’s proclivity to travel was known, the researchers couldn’t explain why it traveled to certain repeats and not to other similar regions, and why the oncoprotein seemed not to be able to act in any type of cell.

Previous studies from our lab have demonstrated increased chromatin accessibility at these repeat DNA regions,” said the study’s first author Nicholas Gomez, PhD, who worked on the project as a doctoral student at UNC. “What we didn’t know is the state of these regions in stem cells. Interestingly, we found that those repetitive regions with the highest accessibility in mesenchymal stem cells – the possible cell of origin in this cancer – predicted the regions that the oncoprotein would bind in the cancer.

Now, Davis and colleagues are focused on identifying treatments that can alter the chromatin targeted by the Ewing sarcoma oncoprotein. As a pediatric oncologist, Davis is motivated to better understand, and possibly to improve treatment for, this cancer and others through research.

I see children with difficult to treat and often incurable cancers in the clinic, as well as children with curable cancers that require months or sometimes years of toxic chemotherapy,” he said. “The impact of these diseases and treatments on children and their families is profound. This appreciation gives me a special drive to tackle studies in the lab that to further our understanding of these diseases, and to use that information to try to advance treatments.

Gomez et al. Widespread Chromatin Accessibility at Repetitive Elements Links Stem Cells with Human Cancer. Cell Reports,  2016; DOI: 10.1016/j.celrep.2016.10.011 [Article]

Cancer patients not getting adequate pain relief

Many terminal cancer patients are not getting adequate pain relief early enough, according to an English study. The researchers found that, on average, terminal cancer patients were given their first dose of a strong opioid such as morphine just nine weeks before their death.

Researchers at Leeds University found that, on average, terminal cancer patients were given their first dose of a strong opioid such as morphine just nine weeks before their death. Yet many people with terminal cancer suffer with pain a long time before that, the researchers said.

We have identified for the first time the relatively late onset and short duration of strong opioid treatment in cancer patients prior to death,” said lead study author Dr Lucy Ziegler, a senior research fellow in palliative care at the University of Leeds.

This pattern of prescribing does not match population data which points to earlier onset of pain. Nine weeks before death is considered late in the course of the cancer trajectory. Although the prevalence of pain is higher in patients with advanced cancer and towards the end of life, for many patients pain is experienced at many stages throughout the illness. In fact, pain is the most common presenting symptom at diagnosis. Our research highlights the need to prioritise earlier access to effective pain management for patients with advanced cancer.”

The research team used UK Cancer Registry data to study a sample of 6,080 patients who died of the disease between 2005 and 2012. They analysed the anonymised corresponding primary care medical records of the patients to find out their prescription history. They found that 48 per cent of the patients were issued a prescription in general practice (primary care) for a strong opioid medication, such as morphine, during the last year of their life. The median interval between first prescription and death was nine weeks.

We examined whether late diagnosis could account for this, but median survival for our sample from diagnosis was 60 weeks, suggesting that most opioid prescribing in fact occurred late in the trajectory between diagnosis and death, regardless of cancer duration,” said Mike Bennett, a professor of palliative medicine at the University of Leeds, who co-authored the research.

In addition, over 90 per cent of all patients in the cohort had received some form of cancer treatment, therefore it was not the absence of a cancer diagnosis or poor engagement with cancer services that hindered timely access to an opioid.

The study found that over-60s were more likely to be prescribed drugs late than younger people, while those who died in a hospice (rather than in hospital, at home or in a care home) were more likely to have been prescribed drugs earlier. The research team, whose study is published in the medical journal Pain, said efforts to improve treatment of cancer pain may be being hindered by concern over the ongoing ‘opioid epidemic’.

They cited NHS data which showed that overall opioid prescribing increased by 466 per cent between 2000 and 2010, but only increased by 16 per cent for patients with cancer. Although the University of Leeds researchers did not examine pain severity, previous studies have found that up to 86 per cent of patients with advanced cancer will experience pain.

Within the advanced cancer population there is a need to develop mechanisms to improve pain assessment and initiate a more proactive approach to prescribing, particularly for older patients,” said Dr Ziegler.

Effective pain control is fundamental to good quality of life. For patients who are approaching the end of their lives it is crucially important we strive to get this right and that we help them achieve the best quality of life possible. One mechanism to achieve this may be through earlier integration of specialist palliative care and we are exploring in a related study funded by Yorkshire Cancer Research whether contact with palliative care services improves access to opioids.”

Ziegler et al. Opioid prescribing for patients with cancer in the last year of life. PAIN, 2016; 1 DOI:10.1097/j.pain.0000000000000656 [Abstract]

How Chinese medicine kills cancer cells

Researchers at the University of Adelaide have shown how a complex mix of plant compounds derived from ancient clinical practice in China – a Traditional Chinese Medicine – works to kill cancer cells.

Compound kushen injection (CKI) is approved for use in China to treat various cancer tumours, usually as an adjunct to western chemotherapy – but how it works has not been known. This study, published in the journal Oncotarget, is one of the first to characterise the molecular action of a Traditional Chinese Medicine rather than breaking it down to its constituent parts.

Most Traditional Chinese Medicine are based on hundreds or thousands of years of experience with their use in China,” says study leader, Professor David Adelson, Director of the Zhendong Australia – China Centre for the Molecular Basis of Traditional Chinese Medicine.

“There is often plenty of evidence that these medicines have a therapeutic benefit, but there isn’t the understanding of how or why. If we broke down and tested the components of many Traditional Chinese Medicines, we would find that individual compounds don’t have much activity on their own. It’s the combination of compounds which can be effective, and potentially means few side-effects as well.”

This is one of the first studies to show the molecular mode of action of a complex mixture of plant-based compounds — in this case extracts from the roots of two medicinal herbs, Kushen and Baituling — by applying what’s known as a systems biology approach. This is a way of analysing complex biological systems that attempts to take into account all measurable aspects of the system rather than focussing on a single variable.”

The Zhendong Australia China Centre for Molecular Traditional Chinese Medicine was established at the University of Adelaide in 2012 in a collaboration with the China-based Shanxi College of Traditional Chinese Medicine and Zhendong Pharmaceutical Company. The Centre was established with a donation by the Zhendong Pharmaceutical Company, with the aim of understanding how Traditional Chinese Medicine works, and the long-term aim of possible integration into western medicineThe researchers used high-throughput next generation sequencing technologies to identify genes and biological pathways targeted by CKI when applied to breast cancer cells grown in the laboratory.

We showed that the patterns of gene expression triggered by CKI affect the same pathways as western chemotherapy but by acting on different genes in the same pathways,” says Professor Adelson.
These genes regulate the cell cycle of division and death, and it seems that CKI alters the way the cell cycle is regulated to push cancer cells down the cell death pathway, therefore killing the cells.”
Professor Adelson says this technique could be used to analyse the molecular mechanisms of other Traditional Chinese Medicines, potentially opening their way for use in western medicine.

Qu et al. Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics. Oncotarget,  2016; DOI:10.18632/oncotarget.11788 [Abstract]

Music demonstrated to alleviate cancer patients’ symptoms

We’ve all heard of laughter being the best medicine, but what about music?

A systematic review published by the Cochrane Library found that there is significant evidence that music interventions help alleviate symptoms of anxiety, pain and fatigue in cancer patients, while also boosting their quality of life.

Led by Joke Bradt, PhD, associate professor in Drexel University’s College of Nursing and Health Professions, a team looked into studies that examined the impact of music therapy (a personalized music experience offered by trained music therapists) and music medicine (listening to pre-recorded music provided by a doctor or nurse) on psychological and physical outcomes in people with cancer.

We found that music therapy interventions specifically help improve patients’ quality of life,” explained Bradt. “These are important findings as these outcomes play an important role in patients’ overall well-being.

A total of 52 trials were examined in the review, constituting of 3,731 participants with cancer. Twenty-three of the trials were categorised as music therapy and the remaining 29 were classified as music medicine interventions. Overall, one of the most impactful findings was that music interventions of all kinds resulted in a moderate-to-strong effect in reducing patients’ anxiety.

When it came to pain reduction, the researchers found a large treatment benefit; for fatigue, a small-to-moderate treatment effect was found. Small reductions in heart and respiratory rates, as well as lowered blood pressure, were also linked to music interventions.

The results of single studies suggest that music listening may reduce the need for anesthetics and analgesics, as well as decreased recovery time and duration of hospitalization, but more research is needed for these outcomes,” according to Bradt and her co-authors.

When comparing music therapy to music medicine, the team saw a moderate increase in patients’ quality of life when music therapy was applied. There was not a similar effect in the case of music medicine interventions.

“Both music medicine and music therapy interventions play an important role in cancer care but we didn’t quite know yet which interventions may be best suited for which type of outcome,” Bradt said
.
In light of the benefits to cancer patients’ quality of life, and specifically their levels of anxiety, pain and fatigue, the researchers hope music interventions will become more widespread.

We hope that the findings of this review will encourage health care providers in medical settings to seriously consider the use of music therapy in the psychosocial care of people with cancer,” Bradt said.

Bradt et al. Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database of Systematic Reviews 2016;DOI: 10.1002/14651858.CD006911.pub3 [Article]

Study shows broccoli may offer protection against liver cancer

Consumption of broccoli has increased in the United States over the last few decades as scientists have reported that eating the vegetable three to five times per week can lower the risk of many types of cancer including breast, prostate, and colon cancers.

A new study from the University of Illinois reports that including broccoli in the diet may also protect against liver cancer, as well as aid in countering the development of fatty liver or nonalcoholic fatty liver disease (NAFLD) which can cause malfunction of the liver and lead to hepatocellular carcinoma (HCC), a liver cancer with a high mortality rate.

The normal story about broccoli and health is that it can protect against a number of different cancers. But nobody had looked at liver cancer,” says Elizabeth Jeffery, a U of I emeritus professor of nutrition. “We decided that liver cancer needed to be studied particularly because of the obesity epidemic in the U.S. It is already in the literature that obesity enhances the risk for liver cancer and this is particularly true for men. They have almost a 5-fold greater risk for liver cancer if they are obese.”

Jeffery says that the majority of the U.S. population eats a diet high in saturated fats and added sugars. However, both of these are stored in the liver and can be converted to body fat. Consuming a high-fat, high-sugar diet and having excess body fat is linked with the development of NAFLD, which can lead to diseases such as cirrhosis and liver cancer.

Previous research suggests that broccoli, a brassica vegetable containing bioactive compounds, may impede the accumulation of fat in the liver and protect against NAFLD in mice. Therefore, Jeffery and her team wanted to find out the impact of feeding broccoli to mice with a known liver cancer-causing carcinogen. The researchers studied four groups of mice; some of which were on a control diet or the Westernized diet, and some were given or not given broccoli.

We wanted to look at this liver carcinogen in mice that were either obese or not obese,” Jeffery explains. “We did not do it using a genetic strain of obese mice, but mice that became obese the way that people do, by eating a high-fat, high-sugar diet.

Although the researchers were predominantly interested in broccoli’s impact on the formation and progression of cancerous tumors in the liver, Jeffery explained that they also wanted to observe the health of the liver and how the liver was metabolizing lipids because of the high-fat diet. “There is almost no information about broccoli and high-fat associated diseases,” she says.

The study shows that in mice on the Westernized diet both the number of cancer nodules and the size of the cancer nodules increased in the liver. But when broccoli was added to the diet, the number of nodules decreased. Size was not affected.

That was what we really set out to show,” Jeffery says. “But on top of that we were looking at the liver health. There are actually two ways of getting fatty liver; one, by eating a high-fat, high-sugar diet and the other by drinking too much alcohol. In this case, it is called non-alcoholic fatty liver, because we didn’t use the alcohol. And it is something that is becoming prevalent among Americans. This disease means you are no longer controlling the amount of fat that is accumulating in your liver.”

With NAFLD, lipid globules form on the liver. During the study, the researchers observed these globules in the livers of the mice on the Westernized diet. “We found that the Westernized diet did increase fatty liver, but we saw that the broccoli protected against it. Broccoli stopped too much uptake of fat into the liver by decreasing the uptake and increasing the output of lipid from the liver,” she says.

Jeffery notes that adding broccoli to the diet of the mice did not make them “thin,” or affect their body weight, but it did bring the liver under control, ultimately making them healthier. “This is one of the things that makes this very exciting for us,” she says. “I think it’s very difficult, particularly given the choices in fast food restaurants, for everybody to eat a lower-fat diet. But more and more now you can get broccoli almost everywhere you go. Most restaurants will offer broccoli, and it’s really a good idea to have it with your meal,” Jeffery adds.

Jeffery’s previous research shows that eating broccoli freshly chopped or lightly steamed is the best way to get to the vegetables’ cancer-fighting compound, sulforaphane. Although the researchers only used broccoli in the study, Jeffery adds that other brassica vegetables, such as cauliflower or Brussel sprouts, may have the same effect.

Chen et al. Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet. J. Nutr. 2016;146:542-550 doi: 10.3945/​jn.115.228148 [Abstract]

Cancer overtakes cardiovascular disease as UK’s No. 1 killer – but only among men

Cardiovascular disease still primary cause of death among women

Cancer has overtaken cardiovascular disease, which includes heart disease and stroke, as the UK’s No 1 killer- but only among men, reveals research published online in the journal Heart. Cardiovascular disease is still the most common cause of death among women, and kills more young women than breast cancer, the figures show.

The researchers used the latest nationally available data (2012-13) for each of the four UK countries and the Cardiovascular Disease Statistics 2014 report compiled for the British Heart Foundation (BHF) to quantify the prevalence of cardiovascular disease, and find out how it’s treated, how much it costs, and how many deaths it causes. Cardiovascular disease includes coronary heart disease, stroke, high blood pressure, circulatory system disease, and other vascular/arterial disease.

The researchers analysed entries to the Clinical Practice Research Datalink GOLD database, the world’s largest repository of anonymised records for primary care, plus information from the family doctor (GP) quality improvement scheme known as QOF, and figures on episodes of inpatient hospital care. The analysis indicated that just short of 2.3 million people were living with some form of coronary heart disease in 2012. Around half a million were living with heart failure and a further 1.1 million were living with abnormal heart rhythm (atrial fibrillation).

England had the lowest prevalence of all cardiovascular conditions out of the four UK countries. But there were regional variations, with higher rates of cardiovascular disease in the North of England than in the South of the country. Scotland had the highest prevalence of coronary heart disease, stroke, and peripheral vascular disease, while Wales had the highest prevalence of high blood pressure, heart failure, and atrial fibrillation.

For the first time since the middle of the 20th century, cancer overtook cardiovascular disease as the primary cause of death in 2012. The proportion of deaths attributable to cancer was 29% while cardiovascular disease accounted for 28%.

But this was only true of men; cardiovascular disease still killed more women than cancer.

Almost one in three deaths (32%) in men were caused by cancer compared with 29% for cardiovascular disease. The equivalent figures were 27% and 28%, respectively, for women.

Cardiovascular disease accounted for a total of nearly 42,000 premature deaths (before the age of 75) in 2012, accounting for more than one in four premature deaths in men and around one in five (18%) in women. But it still killed more young women than did breast cancer.

Once again, there were wide regional variations in death rates. There were higher rates in Scotland (347/100,000 of the population) and the North of England (320/100,000), and lower rates in the South of England. The City of Glasgow topped the league table for death rates from cardiovascular disease for all ages, including premature deaths.

The number of surgical procedures and drugs prescribed to treat and prevent cardiovascular disease has risen substantially over the past two decades, and in 2012-13 the NHS spent just under £7 billion in England alone on cardiovascular disease, the largest chunk of which was spent on hospital care.The equivalent cost in Wales was £442.3 million, £393 million in Northern Ireland, and more than £750 million in Scotland.

Cardiovascular disease remains a substantial burden to the UK, both in terms of health and economic costs,” write the researchers, highlighting the “stark regional inequalities in the mortality and prevalence of cardiovascular disease.”

In a linked editorial, Dr Adam Timmis, of the NIHR Cardiovascular Biomedical Research Unit at Barts Health, London, describes the more than 40% drop in cardiovascular disease death rates since 1960 as “among the greatest public health triumphs in the past 50 years.” But the continuing North-South divide is a “stain on the UK’s public health record,” he writes.

The BHF report provides a timely reminder that in young women too cardiovascular disease kills more women than breast cancer. Most of these deaths in young women are caused by myocardial infarction heart attack which is largely preventable through modification of risk factors,” he points out.

And if the national effort put into the detection of breast cancer could be matched in protecting young women against myocardial infarction many more lives would probably be saved,” he insists.

Bhatnagar et al. The epidemiology of cardiovascular disease in the UK 2014. Heart. 2015; doi:10.1136/heartjnl-2015-307516 [Article]