Q&A: Acrylamide - a reason to give up browned toast and roast potatoes?

Links

http://www.bbc.co.uk/news/health-38691915 - news report of FSA report:

https://www.food.gov.uk/science/acrylamide-0

https://medium.com/wintoncentre/how-dangerous-is-burnt-toast-c5e237873097#.iwznbm6cz - Prof. David Spiegelhalter comments.

http://www.cancerresearchuk.org/about-cancer/causes-of-cancer/diet-and-cancer/food-controversies#food_controversies0 - Cancer Research UK comments.

http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2015.4104/epdf - European Food Safety Authority report

https://en.wikipedia.org/wiki/Maillard_reaction - chemistry of Maillard [browning] reaction

Does Aspirin prevent Breast Cancer?

reposted from: http://www.forbes.com/sites/melaniehaiken/2013/04/23/new-cancer-prevention-secret-aspirin/ | FASEB Abstract by Gargi Maity, Archana De Snigdha, Banerjee Amlan Das and Sushanta Banerjee - Kansas City

crabsallover highlights, key points, comments / links.


Forbes
Taking a low dose of aspirin every day could have the potential to prevent breast cancer or stop it in its tracks.

That was the news over the weekend from the annual meeting of the American Society for Biochemistry and Molecular Biology in Boston, where a team of researchers from the Veterans Affairs Medical Center in Kansas City and the University of Kansas Medical Center presented evidence demonstrating the effects of aspirin against two types of breast cancer.

One of them, so-called “triple negative” cancer, is the most aggressive type of breast cancer and also the most dangerous because it often doesn’t respond to conventional therapies.


FASEB Abstract
Aspirin, a classical non-steroidal anti-inflammatory drug (NSAID) is widely used to reduce pains and fever. Epidemiological and experimental studies suggested that Aspirin use reduces the risk of different cancers including breast cancer and may be used as a chemopreventive agent against breast cancer and other carcinogenesis. These studies have raised the tempting possibility that Aspirin could serve as a preventive medicine for breast cancer. However lack of in-depth knowledge of the mechanism of action of Aspirin reshapes the debate of risk and benefit of Aspirin in prevention of breast cancer. Our aim is to investigate effects of Aspirin on pathophysiological events like epithelial to mesenchymal transition (EMT), migration, stemness of cell in breast cancer cells. Our studies using in vitro and in vivo tumor xenograft model show a strong beneficial effects of Aspirin in prevention of breast carcinogenesis. We find Aspirin not only prevents breast tumor cell proliferation in vitro and tumor growth in xenograft mouse model, it also significantly inhibits other pathophysiological events in breast cancer such as EMT, cell migration as well as reprogramming of stemness in breast cancer cells. Collectively our studies suggest that intake of an ASPIRIN a day might offer additional avenues for breast cancer prevention and treatment.

Limiting processed meat consumption 'could prevent three per cent of premature deaths'

source: http://www.nhs.uk/news/2013/03March/Pages/Diet-high-in-processed-meat-threatens-health.aspx

I conclude I should eat ave. 50g/day red meat and 20g/day processed meat; 70g/day total meat (Dept. Health guideline)

Diet high in processed meat 'threatens health'

Processed meats include bacon, sausages and salami

The big health news of the week is the claim that eating a diet high in processed meat can increase the risk of premature death due to cancer and heart disease. 

The current media scare stems from a large Europe-wide study looking at diet and mortality, involving just under half a million people who were followed for an average of 12.7 years.

One of the main findings was that people in the study who ate the most processed meat (160g or more per day) had a 44% increased risk of dying during follow-up compared to those who ate the least (10g or less).

The link to red meat was less conclusive.

The researchers estimated that if we all ate less than 20g of processed meat (which is around a single small piece of bacon) a day, then 3.3% of all deaths could be avoided – which is where the media reports came from that processed meat is responsible for 1 in 30 deaths.

However, an important limitation (rightly highlighted by the authors) is the possibility that other health and lifestyle factors could be contributing towards premature death risks.

Nevertheless, the study does highlight the importance of eating a healthy balanced diet, containing a high amount of fruit and vegetables.

Processed meat

Processed meat refers to meat that has been preserved by smoking, curing, salting or adding preservatives. This includes sausages, bacon, ham, salami and pâtés.

Processed meat is usually high in fat and cholesterol, which can increase heart disease risk. A diet high in processed meat (regularly eating more than 90g a day) has also been linked to an increased risk of bowel cancer.

This study found that people who ate more than 160g a day had the highest risk of premature death – this is equivalent to eating a full English breakfast every morning.

The Department of Health recommends that you do not eat more than 70g of red or processed meat a day.

Where did the story come from?

The study was carried out by researchers from the Institute of Social and Preventive Medicine, University of Zurich, Switzerland, and a large number of other institutions across Europe.

Financial support was provided by a range of European organisations including, government, charity and academic institutions.

The study was published in thepeer-reviewed journal BMC Medicine, which is available on an open access basis.

The media stories are generally representative of the findings of this research, with most including the common sense advice that eating an occasional bacon sarnie won’t kill you – just don’t do it every day.

The claims that processed meat is responsible for 1 in 30 deaths are based on the researchers’ estimate that 3.3% of the deaths in this study could have been prevented if all those who took part in the study ate less than 20g of processed meat a day.

What kind of research was this?

Many past observational studies have suggested that high levels of red meat and processed meat consumption could be linked to a range of diseases, including cardiovascular diseases and various cancers, such as bowel cancer.

However, it can be difficult in such studies to exclude the possibility that the effect is not directly due to red and processed meats as such, but is due to the influence of other health and lifestyle factors. For example, people who eat a small amount of red and processed meat may also be eating higher amounts of fruit and vegetables, exercising more, be less likely to be overweight, smoke, or drink excess amounts of alcohol.

In the same vein, people who eat lots of processed meat may have other unhealthy habits such as drinking lots of alcohol and being heavy smokers.

This was a large cohort study using data collected as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

EPIC is an ongoing cohort study including more than 500,000 participants from 10 European countries.

The researchers took data from the EPIC study to look at the association between red meat, processed meat, and poultry meat consumption, and the risk of overall mortality and cause-specific mortality.

What did the research involve?

Men (aged 40 to 70) and women (aged 35 to 70) were recruited to EPIC between 1992 and 2000 (depending on the European study centre). After excluding those with self-reported cancer or heart disease, or those who did not report on smoking status at the time of enrolment, there were 448,568 people in the study.

Dietary assessment was performed slightly differently depending on the country:

• seven countries gave self-administered dietary questionnaires (including data on 300-350 food items)
• three countries administered a similar questionnaire by direct interview
• two of the countries (UK and Sweden) also combined the questionnaires with a seven-day food diary

For the purposes of analysis, they grouped food products as follows:

• red meat (beef, pork, mutton/lamb, horse, goat)
• processed meat (including ham, bacon, sausages, or a small amount of minced meat as part of a ready-to-eat product – processed meat is mainly taken to be red meat, but it could be white as well)
• white meat (poultry, including chicken, hen, turkey, duck, goose, unclassified poultry, and rabbit) 

Various other sociodemographic, health and lifestyle questions were also assessed at recruitment, including age, education, height and weight, medical history, alcohol consumption, and smoking history (current, past or never, including questions on frequency and type of tobacco smoked).

Follow-up of outcomes was to 2005-09, depending on the country, with an average follow-up of 12.7 years. Information on deaths and cause of death was obtained through record linkage with cancer registries, Boards of Health, and death indices in seven countries, and through active follow-up of participants (for example, mail, telephone, and medical records) in three countries.

Information on vital status could be obtained for 98% of the cohort, which is impressive given the size of the study.

Hazard ratios were calculated to examine the association between different types and quantities of meat and processed meat consumption and risk of death.

They adjusted analyses for the following cofounders:

• age
• study centre
• weight and height
• smoking history
• alcohol intake
• overall energy intake
• physical activity levels
• educational level

What were the basic results?

Compared to men and women who ate lower amounts of red and processed meat, those who ate the highest amounts tended to also eat fewer fruit and vegetables, be more likely to smoke, and less likely to have a university degree. Men who ate the highest amounts of red meat also drank more alcohol than those who ate lower amounts. This result was not seen in women.

During the average 12.7 year follow-up, there were 26,344 deaths (6% of the cohort), of these, 37% were due to cancer, 21% due to cardiovascular disease, 4% due to respiratory disease, 3% to digestive tract diseases, and the remainder due to various other causes.

Overall, there was a link between increasing processed meat consumption and risk of all-cause mortality. In the model adjusted for all confounders:

• people who ate the highest amount of processed meat (160g per day) had 44% increased risk of death compared to those who ate 10-20g per day (hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.24 to 1.66)
• people who ate 80-160g a day had 21% increased risk (HR 1.21, 95% CI 1.14 to 1.28) and those who ate 40-80g a day had 9% increased risk (HR 1.09, 95% CI 1.05 to 1.14) compared to those who ate 10-20g per day
• compared to those who ate 10-20g per day, there was no difference in risk with eating 0-10g or eating 10-40g
• overall, eating an additional 50g of processed meat a day gave 18% increased mortality risk (HR 1.18. 95% CI 1.11 to 1.25)
• eating an additional 50g of processed meat a day also gave a 30% increased risk of dying from any cardiovascular disease (HR 1.30, 95% CI 1.17 to 1.45), and an 11% increased risk of dying from any cancer (HR 1.11, 95% CI 1.03 to 1.21)

The link with red meat was not as strong as for processed meat:

• eating the highest intake of red meat (160g per day) was associated with 14% increased risk of all-cause mortality compared to eating 10-20g per day (HR 1.14, 95% CI 1.01 to 1.28)
• people who ate 20-160g of red meat a day were at no higher risk than those who ate 10-20g per day
• people who ate the lowest amount (0-10g a day) also had increased mortality risk compared to those who ate 10-20g per day.
• unlike with processed meat, the researchers found no overall significant increase in mortality risk for eating an additional 50g of red meat a day

There was no link between death risk and poultry consumption.

The researchers estimated that 3.3% of all deaths could be avoided if all people ate less than 20g per day of processed meat.

How did the researchers interpret the results?

The researchers conclude that their analysis supports a ‘moderate association’ between increased processed meat consumption and increased mortality, in particular due to cardiovascular diseases, but also cancer.

Conclusion

This is a useful study examining whether there is an increased risk of dying from any cause, and from specific causes, with increased consumption of red meat and processed meat. The link to red meat was less conclusive, but there appeared to be a consistent link between increasing processed meat consumption and mortality risk.

The study has many strengths, including that it followed a large number of adults from across 10 European countries for an average 12.7 years, with almost complete follow-up.

The study used reliable methods to assess mortality outcomes. Food frequency questionnaires will unavoidably include some inaccuracy (for example, inaccurate recall or estimation of intake).

However, the researchers did attempt to validate the information through a series of 24-hour recalls.

The researchers have adjusted their analyses for age, study centre, weight and height, smoking and alcohol intake, overall energy intake, physical activity levels and educational level.

However, as the authors rightly conclude, the main limitation of the study is that it cannot completely exclude the possibility of residual confounding – that is, that the effects of these demographic, health and lifestyle factors, or others unmeasured, have not been fully accounted for.

These limitations apart, the study provides reasonably good evidence to support the importance of eating a healthy balanced diet, containing a high amount of fruit and vegetables. At the same time, it is important to moderate your consumption of foods high in salt, fat and sugar, which includes many processed foods.

The occasional bacon sandwich or full English breakfast probably won’t do significant damage to your health. But these should be occasional treats and not a staple of your diet. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines

Processed meat 'early death' link. BBC News, March 7 2013

Processed meat scare: a bacon sandwich won't kill you … will it? The Guardian, March 7 2013

Processed meat 'is to blame for one in 30 deaths': Scientists say a rasher of cheap bacon a day is harmful. Daily Mail, March 7 2013

Still fancy the full English? Study links processed meats such as bacon and sausages to risk of early death. The Independent, March 7 2013

Processed meat blamed for one in 30 early deaths. The Daily Telegraph, March 7 2013

Processed Meat Linked To Early Death In Study. Sky News, March 7 2013

Links to the science

Rohrmann S, Overvad K, Bueno-de-Mesquita HB, et al. Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition. BMC Medicine. Published online March 7 2013

reposted from: Cancer Research UK

crabsallover highlights, key points, comments / links.

Cancer News
Limiting processed meat consumption 'could prevent three per cent of premature deaths'
Thursday 7 March 2013

If everyone ate less than 20g of processed meat a day, there would be a three per cent drop in premature deaths from cancer and heart disease, according to new European research.

High consumption of red and processed meat has previously been linked to an increased risk of several types of cancer, particularly bowel cancer, as well as cardiovascular diseases.

The European Prospective Investigation into Cancer and Nutrition (EPIC) study - part-funded by Cancer Research UK - is following the diets, medical records and death certificates of half a million men and women from 10 European countries.

Its latest analysis, published in the journal BMC Medicine, looked at patterns of consumption of meat among participants, and how this related to their cause of death.

Over an average of nearly 13 years, 26,344 study participants died. Of these, 5,556 died of cardiovascular diseases, 9,861 of cancer, 1,068 of respiratory diseases, 715 of digestive tract diseases, and 9,144 of other causes.

Analysis showed that a person's risk of premature death from cancer or heart disease increased with the amount of processed meat they ate, even once other lifestyle variables were factored in.

No link was seen between red meat or poultry.

Those who ate the most processed meat also ate the fewest fruit and vegetables and were more likely to smoke, while men who ate a lot of meat also tended to drink heavily, the study found.

Yinka Ebo, senior health information officer at Cancer Research UK, said: "There's a clear link between eating too much processed meat and bowel cancer, but this study suggests that cutting down on these meats could also reduce the risk of dying prematurely.

"There's no need to abandon meat altogether, but if you eat a lot of processed meat it's worth cutting down by eating smaller and fewer portions, or eating fish, poultry or beans instead," she added.

Copyright Press Association 2013

Rohrmann S, et al. Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition (2013) BMC Medicine

Nonparametric regression curve for the relation of processed meat intake at recruitment with all-cause mortality, European Prospective Investigation into Cancer and Nutrition (EPIC), 1992-2009. Solid line, effect estimate; dotted lines, 95 percent confidence interval.

Rohrmann et al. BMC Medicine 2013 11:63   doi:10.1186/1741-7015-11-63

UK health performance: findings of the Global Burden of Disease Study 2010

reposted from: The Lancet (full text - free article) via Cancer Research UK

crabsallover highlights, key points, comments / links.

Funding: Bill & Melinda Gates Foundation.

Improvements in the UK's health lag behind many other developed nations, a study published in The Lancet has revealed.

Although life expectancy of Britons has increased thanks to six decades of universal healthcare, vastly increased health spending and widespread anti-tobacco initiatives, the UK has failed to keep pace with the 14 other original members of the European Union, Australia, Canada, Norway, and the USA over the past 20 years

While average UK life expectancy has increased by 4.2 years over the last two decades, the nation's premature death rates have dropped at a slower rate than the rest of the other countries.

Using data from the 2010 Global Burden of Disease study, a team of international experts led by Dr Chris Murray, from the University of Washington's Institute for Health Metrics and Evaluation, analysed patterns of ill health and death in the UK. They then ranked them against other high-income countries with similar levels of health expenditure in 1990 and 2010.

Smoking is a large factor in the UK's poor relative performance, alongside alcohol, drug abuse and obesity, with doctors calling for a more joined-up health policy to help educate the public about health lifestyles.

The eight leading causes of death in the UK have remained relatively consistent over the last 20 years, with ischemic heart disease, chronic obstructive pulmonary disease (COPD), stroke, lung cancer and lower respiratory infections continuing to top the list.

Sarah Woolnough, Cancer Research UK's executive director of policy and information, said the findings underlined the need for action.

"We know that smoking, being overweight or obese, poor diet and alcohol consumption all increase the risk of developing cancer," she said.

"Over 40 per cent of cancers in the UK are preventable; of these, tobacco is the single largest cause of cancer responsible for over 60,000 cases in the UK. It is sadly not surprising that lung cancer remains in the top five causes of death in the UK.

That, said Woolnough, highlighted the need for improved public health and early intervention to tackle premature mortality, and to "achieve mortality rates on a par with the best countries in the world".

"As part of this, we are urging the Government to introduce standardised packaging of tobacco, which would make tobacco less attractive, and help prevent a further generation of young people from starting to smoke," she added.

Dr Edmund Jessop, from the UK Faculty of Public Health, said that despite the overall findings, the UK had done "very well" in some areas over the last two decades, citing reduced mortality rates, improved diet and a drop in disability-adjusted life-years.

This meant that the UK had seen significantly lower premature mortality from diabetes, road injuries, liver cancer and chronic kidney diseases

He also pointed out that the UK has some of the strongest tobacco control policies in Europe.

Copyright Press Association 2013

Reference

• Murray C.J., Richards M.A., Newton J.N., Fenton K.A., Anderson H.R., Atkinson C., Bennett D., Bernabé E., Blencowe H. & Bourne R. & (2013). UK health performance: findings of the Global Burden of Disease Study 2010, The Lancet, DOI: 10.1016/S0140-6736(13)60355-4

Figure 3: Age-standardised YLLs relative to comparator countries and ranking by cause in (A) 1990 and (B) 2010
Numbers in cells indicate the ranks of each country for each cause, with 1 representing the best performing country. Countries have been sorted on the basis of age-standardised all-cause YLLs for that year. Causes are ordered by the 30 leading causes of YLLs in the UK. Colours indicate whether the age-standardised YLL rate for the country is significantly lower (green), higher (red), or indistinguishable (yellow) from the mean age-standardised YLL rate across comparator countries, with 95% confidence. YLLs=years of life lost. COPD=chronic obstructive pulmonary disease.

Figure 4
YLDs in the UK by cause and age in 2010
YLDs=years lived with disability.

Figure 7
Burden of disease attributable to 20 leading risk factors for both sexes in 2010, expressed as a percentage of UK disability-adjusted life-years
The negative percentage for alcohol is the protective effect of mild alcohol use on ischaemic heart disease and diabetes.

World Cancer Day 4 February 2013

reposted from: http://www.wcrf.org/policy_public_affairs/world_cancer_day/index.php

crabsallover highlights, key points, comments / links.

 The World Cancer Research Fund global network is delighted to support World Cancer Day organised by the Union for International Cancer Control (UICC).  What do you think causes cancer? We went out on the streets to ask...


Incidence of cancer in developing and developed countries (pdf)

World Cancer Day 2013 (4 February 2013) will focus on Target 5 of the World Cancer Declaration: Dispel damaging myths and misconceptions about cancer, under the tagline “Cancer - Did you know?”. World Cancer Day is a chance to raise our collective voices in the name of improving general knowledge around cancer and dismissing misconceptions about the disease. From a global level, we will be focusing our messaging on the four myths above. In addition to being in-line with our global advocacy goals, we believe these overarching myths leave a lot of flexibility for members, partners and supporters to adapt and expand on for their own needs.

Cancer myths: get the facts

Many people believe that cancer is just ‘bad luck’ or ‘fate’.

The truth is:

• About 2.8 million cases of cancer could be prevented globally every year through choosing a healthy diet, being physically active and maintaining a healthy weight.
• Prevention is the most cost-effective and sustainable way of reducing the cancer burden in the long-term.
• Global, regional and national policies and programmes need to help support people to make better lifestyle choices if cancers caused by alcohol, unhealthy diets and lack of physical activity are to be reduced.

To find out more about other common cancer myths and get the truth see:

Myth 1: Cancer is just a health issue

Truth: Cancer is not just a health issue. It has wide-reaching social, economic, development, and human rights implications.

Myth 2: Cancer is a disease of the wealthy, elderly and developed countries

Truth: Cancer is a global epidemic. It affects all ages and socio-economic groups, with developing countries bearing a disproportionate burden.

Myth 3: Cancer is a death sentence

Truth: Many cancers that were once considered a death sentence can now be cured and for many more people, their cancer can be treated effectively.

Myth 4: Cancer is my fate

Truth: With the right strategies, a third of the most common cancers can be prevented.

Downloads from the UICC website:

Fact Sheets
Posters

Getting to the root of tumour blood vessels

reposted from: http://scienceblog.cancerresearchuk.org/2013/01/18/getting-to-the-root-of-tumour-blood-vessels/

crabsallover highlights, key points, comments / links.

Posted on January 18, 2013 by Marianne Baker

This entry is part 2 of 3 in the series Microenvironment

Blood vessels are the ‘roots’ of a tumour. Image source: Wikimedia Commons

In the first of this series we explained how the ‘neighbourhood’, or microenvironment, around a cancer affects how it grows and spreads.

In this next post we’re taking a look at how blood vessels grow into, and feed, a tumour.

Angiogenesis

As we’ve said before, a tumour can be thought of as a ‘rogue organ’ in the body – not one that is useful to us, but one that has the same requirements as any other. This includes a network of blood vessels (vasculature), supplying the cancer cells with oxygen and nutrients, and removing waste products. And, in the case of cancer, enabling it to survive, grow, and spread around the body.

But while the blood supply feeding our healthy tissues grows as we develop in the womb, a tumour has to ‘plumb in’ its own blood supply from nearby blood vessels – a process known as angiogenesis.

And because angiogenesis is so fundamental to how cancers grow and spread, it’s an exciting focus for cancer researchers all over the world.

Getting to the root of the problem

Cancers are a bit like weeds in the garden – they look like their neighbours but take up space and out-compete other plants, and have the potential to run riot over the entire garden if left uncontrolled.

As all good gardeners know, the best way to get rid of weeds for good is to destroy their roots. Fail to do this, and they’ll just start growing again.

In a similar way, blood vessels are the ‘roots’ of a tumour, feeding it and allowing it to grow bigger. Targeting these roots and cutting off the blood supply should therefore be a good approach for treating cancer.  And that’s exactly what many researchers in the field of tumour angiogenesis are trying to do.

Targeting tumour blood vessels

The idea of targeting blood vessels to treat cancer is based on the discovery that most blood vessels in adults are quiescent - in other words, they’ve done all the growing they need to and have then stopped.

But there are a couple of exceptions.  Every month, new blood vessels grow in a woman’s uterus during her menstrual cycle. And every time a cut heals, new vessels grow back during that process. But (in theory at least) treatments targeting new blood vessel growth should be relatively free of side-effects, because they’re designed to target the growing blood vessels in tumours and not the established quiescent vessels.

Also, the components of blood vessels within tumours aren’t actually cancerous themselves – they’re healthy cells that have been hijacked by a cancer to do things they usually wouldn’t. This means they should be less likely to develop resistance to treatments, because they’re less able to mutate and evolve in the same way as cancer cells. So – at least in theory – this seems like another plus point.

Some drugs that target tumour blood vessels have already been developed, including “first generation” therapies such as bevacizumab (Avastin), which blocks a molecule called VEGF that is produced in large amounts by tumours to provoke angiogenesis.

Unfortunately, bevacizumab didn’t show the impressive results in cancer patients that might have been expected from early lab studies (although it fared better in combination with other chemotherapy drugs). And these types of drugs haven’t had as few side effects as researchers had hoped.

In the 30 years since VEGF was discovered, many Cancer Research UK scientists have contributed to our growing understanding of how it – along with a multitude of other molecules – is important in angiogenesis. As a result, rather than focusing on VEGF alone, other molecular messengers can be targeted at the same time to try to avoid resistance and increase the drugs’ effectiveness. “Second/third generation” anti-angiogenic therapies such as sunitinib (Sutent) and sorafenib (Nexavar) have made it to the clinic, but researchers are still working out how best to use them.

So while the idea of blocking blood vessel growth once seemed straightforward, the reality turned out not to be quite so simple. But why?

What’s so special about tumour blood vessels?

Researchers now think that the key to targeting blood vessels in tumours lies in understanding what makes them different from healthy ones. While the cells that make up tumour blood vessels are themselves quite normal (in that their genetic information isn’t damaged like it is in cancer cells) the blood vessels as a whole are very messed up.

There are two main types of cells that make up the tiny blood vessels (called capillaries or microvessels) found in tumours: endothelial cells that line the walls of vessel tubes, andpericytes, which support them around the outside.

A Roman Phalanx – a little bit like blood vessels. Image source: Wikimedia Commons

In healthy capillaries, these cell types are quite well-organised. The endothelial cells fit together like the shields of a Roman phalanx and the pericytes support them at key points, helping to stabilise the structure.

But inside tumours, there are big gaps in the walls of the capillaries.  Endothelial cells come and go as they please, sometimes the pericytes don’t show up to help out, and sometimes even cancer cells get involved and pretend to be endothelial cells. The tubes have irregular sizes and are chaotically organised, twisting tortuously about instead of lining up neatly like healthy capillaries.

This makes a tumour’s blood vessels very leaky and inefficient, causing them to release signals that drive even more blood vessel growth to feed the growing tumour in a vicious cycle.

Unexpected effects

To try and understand the disappointing results of anti-angiogenic drugs, scientists took a closer look at what was happening to blood vessels inside tumours in response to the treatment. What they found was unexpected (although our researchers Alan Le Serve and Kurt Hellmann had actually predicted this might happen back in the 1970s). Instead of destroying tumour blood vessels, anti-angiogenic drugs seem to make the strange and disordered capillaries become more normal.

At first, people thought this spelled disaster for the whole concept of anti-angiogenic therapy – surely if the treatment makes the tumour blood vessels better at their job, the cancer will just grow and spread faster. This is the opposite of what doctors and their patients want!

But on closer inspection, this ‘normalisation effect’ actually looks like it might be a positive thing – if we can catch it at just the right time. Here’s why:

• Making tumour blood vessels better at delivering nutrients and oxygen to the tumour can have positive effects on some cancer treatments. For example, if chemotherapy is given together with anti-angiogenics, the more efficient blood flow means more of the chemo drug can get to more of the cancer cells to kill them. This explains why drugs like bevacizumab seem to work better when given alongside chemo.
• Because of their disorganised blood supply, many tumours have relatively low oxygen levels – a phenomenon known as hypoxia – which seems to protect cancer cells from being destroyed by radiotherapy. Stabilising blood vessels means that more oxygen gets into the tumour, raising oxygen levels inside it. This could help to make radiotherapy more effective.
• As tumour blood vessels become more normal, they seem to attract more supporting pericytes, which help to secure capillaries against wandering cells. Some researchers have shown that this could reduce the risk of cancer spreading (metastasis), which happens when cancer cells enter the bloodstream and travel to another site in the body. If entering blood vessels becomes more difficult for cancer cells, this could be a good way to protect against cancer spread.

Combining all these things together, it seems that while anti-angiogenics might not be useful in the way we originally thought (by killing blood vessels and starving tumours), they might instead make the other kinds of treatments even more effective.

Where next?

Researchers all over the world – including those funded by Cancer Research UK – are now applying these new insights in the hunt for life-saving cancer treatments. Here are just a few examples of our pioneering work in this area:

• Professor Kairbaan Hodivala-Dilke at the Barts Cancer Institute in London is determined to bring cancer therapies based on angiogenesis to the clinic. Work in her lab looking a Down’s syndrome – a phenomenon apparently unrelated to cancer – has helped us understand more about tumours and blood vessel growth.

• Professor Adrian Harris heads a team at Oxford University. Their cutting-edge research aims to uncover more about how tumours attract a blood supply and the characteristics of low-oxygen tumour environments, turning this knowledge into improved cancer therapies. Professor Harris’ work has contributed to our current understanding of the famous blood vessel growth-stimulator VEGF, and another molecular messenger called delta-like 4 (DLL4). Their research has also picked apart other key features of tumours such as hypoxia and prompted the development of new cancer treatments.

• Professor David Tuveson, who until recently was based at the Cancer Research UK Cambridge Research Institute, made a big step forward in understanding the role of blood vessels in pancreatic cancer – a  deadly disease for which new treatments are urgently needed.

In pancreatic cancer, the tumour cell environment is very dense. The leakiness of blood vessels leads to a very high fluid pressure within the tumour that collapses capillaries and makes blood flow almost non-existent. This means that chemotherapy drugs (which are carried in the bloodstream) simply can’t get into the tumour.

Professor Tuveson’s team found that the solution to this problem may lie in using a combination of drugs, including one that breaks down the dense packing within the tumour. This helps to open up the tumour blood vessels, allowing chemotherapy drugs to get through.

Hope for the future

Researching anti-angiogenic therapy has been somewhat of a rollercoaster of hope, disappointment and renewed optimism.

At first it seemed like a hugely promising target for all solid tumours, then the results from the clinic didn’t live up to expectations. Now it appears they could be really effective after all, but maybe not in the ways we expected. Only further research can tell us exactly how these potentially powerful therapies can be put to work to beat cancer.

But blood vessel growth isn’t the only area we’re seeing interesting developments in: there’s also the immune system, and cancer spread, so watch this space for more posts on the tumour microenvironment.

Marianne

• Marianne Baker did her PhD at Barts Cancer Institute, funded by Cancer Research UK

Cancer - the tumour microenvironment

reposted from: http://scienceblog.cancerresearchuk.org/2013/01/11/getting-to-know-the-neighbours-the-tumour-microenvironment/

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Getting to know the neighbours – the tumour microenvironment

Posted on January 11, 2013 by Marianne Baker

This entry is part 1 of 3 in the series Microenvironment

Tumour cells don’t live in isolation

Despite the huge progress that has been made over recent decades, more than 150,000 people lose their lives to cancer every year in the UK, usually because the disease has spread through their body.

Understanding why this happens – and how we can treat tumours once they have spread – is crucial if we are to beat cancer.

Cancer is not just one but hundreds of different diseases, depending on where in the body it started and the underlying molecular faults that drive it.

Over the years, many researchers have poured their efforts into understanding individual types of cancer -  such as the recent work from Cancer Research UK’s Professor Carlos Caldas showing that breast cancer can be divided into ten distinct types – as well as searching for the fundamental characteristics of cancer cells (for example, our very own Sir Paul Nurse and Sir Tim Hunt’s Nobel prize-winning work on understanding how all cells divide).

Much of the effort in developing new cancer treatments has focused on identifying and targeting specific molecules in cancer cells – good examples of this approach in action are revolutionary ‘targeted’ drugs like breast cancer drug trastuzumab (better known as Herceptin) and leukaemia drug imatinib (also called Glivec).

But as well as this focus on cancer cells themselves, it’s becoming increasingly clear that tumours are more than just collections of rogue cells. Blood vessels, immune cells and other healthy tissues are hijacked to support a tumour, helping it grow, spread and resist treatment.

Researchers are increasingly turning their attention to this ‘bad neighbourhood’ around a around a tumour, to understand how it can be brought back under control to treat cancer more effectively.

There’s more to cancer than cancer cells

Solid tumours (cancers excluding those affecting the blood) can be thought of as being a bit like a rogue organ in the body, rather than a growing cluster of identical cancer cells.

So modern-day cancer research often involves studying this whole system in order to further our understanding of cancer and tackle it effectively.

All the different types of cells within tumours, the proteins that surround them and the conditions they create together are referred to by scientists as the tumour microenvironment.

This ‘neighbourhood’ includes blood vessels and lymphatic vessels (which carry a fluid called lymph, containing many of the components of our immune system). There are also cells and molecules from the immune system itself, and wound-healing cells called fibroblasts, as well as a sticky protein ‘glue’ (known as the matrix) that supports all of the cells and stops them from drifting apart when they need to be held together.

Can we target the microenvironment to treat cancer?

All of the different parts of the microenvironment play their own roles in helping tumours to grow, and while their importance is still to be fully understood, research is going strong in this area. Through looking in greater detail at the tumour microenvironment, we’ll be able to understand more about how tumours grow and spread, and how we can stop them.

For a personal view from one of our researchers working in this area, check out this interview with Professor Fran Balkwill at the Barts Cancer Institute in London. Professor Balkwill gives us her views on why it’s important to think about treating cancer and its environment together, and why she’s excited about it.

But that’s not all. Because this is such a hot topic in research, we’ve got a series of postscoming up about the tumour microenvironment and its importance in cancer research today, covering blood vessels, cancer spread and inflammation.

Watch out for them over the coming weeks, to find out more about this fascinating and important area.

Marianne

• Marianne Baker did her PhD at Barts Cancer Institute, funded by Cancer Research UK