New hope for better treatment for a rising cancer

Poor diet, too much alcohol, smoking and increasing obesity could be leading to an epidemic of oesophageal and upper stomach cancer, according to a leading UK team of specialists at The University of Nottingham and Nottingham University Hospitals.

The Nottingham Gastro-Oesophageal Cancer Research Group has been carrying out intensive research over the past five years to try to improve the treatment of this cancer. A major part of the research is published today in the British Journal of Cancer. The work has been prompted by a large increase in the incidence of cancer of the oesophagus (gullet) and upper stomach over the past 40 years.

According to Cancer Research UK statistics, rates of oesophageal adenocarcinoma and gastro-oesophageal (GOJ) adenocarcinoma have been increasing in the UK. Since the 1970s the incidence of this cancer has increased by 50 per cent in men and 20 per cent in women. Indeed the reported rates for white men in the UK are now the highest in the world.

Doctors believe changes in diet and lifestyle are the key factors behind the rapid rise in the number of cases. This new research is aimed at providing a better treatment and prognosis for a cancer that is historically not survivable past five years from diagnosis. Current standard treatment for potentially operable cancer consists of a 12 week intensive course of powerful chemotherapy, followed by surgery if the tumour is operable, and then a second 12 week course of chemotherapy. This prolonged, intense course of chemotherapy treatment is potentially toxic, impacts on quality of life and is likely to be beneficial only in those patients who respond to chemotherapy.

The Nottingham-based research using molecular cancer pathology and DNA protein expression techniques on tumour samples from around 250 patients after surgery has shown that only between 40 per cent and 50 per cent of these adenocarcinomas actually respond to the chemotherapy. The research has effectively tested a very promising monitoring test during treatment so that doctors can assess whether and how far the tumour is regressing during chemotherapy. In addition, the research has also identified a promising protein marker involved in DNA repair in cancer cells that predicts resistance to chemotherapy in tumours.

The new information could empower doctors to decide whether to recommend a second course of powerful chemotherapy after surgery. The research also paves the way for wider and more specialised clinical trials for this cancer which will monitor patients in real-time, rather than using past samples, and which could lead to new combinations of chemotherapy, including the new breast cancer drug, Herceptin, which has recently been proven to be effective in gastro-oesophageal cancers.

Dr Srinivasan Madhusudan, Clinical Associate Professor & Consultant in Medical Oncology at Nottingham University Hospitals and the University’s School of Molecular Medical Sciences, said: “Recent scientific advances have given real hope for patients with gastro-oesophageal cancers. The Nottingham Upper Gastrointestinal Cancer Group is a multidisciplinary research team consisting of Oncologists, Surgeons, Pathologists and Radiologists. We aim to exploit the ‘new science’ for patient benefit. This study published online today in the British Journal of Cancer provides evidence that it may be possible to tailor gastro-oesophageal cancer treatments based on ‘new’ biology. We are planning a larger prospective multicentre study to confirm these findings and we believe will have major clinical impact on how we treat these aggressive tumours in the future.”

Source:http://communications.nottingham.ac.uk/News/

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Unravelling the health-giving properties of fruit and veg

Scientists at The University of Nottingham are to use their share of a unique £6.5m research award to discover which genes control the health promoting properties of fruit and vegetables.

As part of a cross-channel partnership to enhance international collaboration in Systems Biology Graham Seymour, Professor of Plant Biotechnology, and Charlie Hodgman, Director of the Centre for Plant Integrative Biology, will be working on a systems biology approach to understand the metabolic networks underlying health based quality traits in tomato fruit.

With their award of nearly £300,000 from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Agence Nationale de la Recherche (ANR) the bio-scientists will be working in collaboration with Royal Holloway University of London, the National Scientific Research Centre, Paris (CNRS) and the Plant Genomics Centre, INRA, Evry, near Paris.

Professor Seymour said: “The health promoting properties of diets rich in fruit and vegetables has been attributed to the synergistic effects of various phytochemicals in food such as vitamins, flavonoids and carotenoids.

"This project aims to study an experimental model tomato that has very high levels of these health-related compounds. The researchers aim to use a systems biology approach to integrate information at many different levels about the tomato and to produce a predictive model of how the formation of these phytochemicals is controlled.”

Professor Hodgman said: "The long-term intention of the Centre for Plant Integrative Biology which is funded by the BBSRC and the Engineering and Physical Sciences Research Council is to apply work and techniques developed on model plant organisms to crop species. This tomato work is a very welcome first step."

BBSRC and ANR, the leading public life-science funding agencies in the UK and France, are funding a total of 10 new projects involving 22 different universities and institutes in the UK and France.

Each project has at least one UK and one French partner institution and the initiative aims to build European collaboration in Systems Biology. BBSRC has already invested over £70m in UK and European Systems Biology initiatives and the UK is one of the world leaders in this new and growing approach to tackling bioscience problems.

Systems biology is a revolution in the way bioscientists think and work. It brings together researchers across different disciplines, combining theory, computer modelling and experiments. Systems biology will make the outputs of bioscience research more useful and easier to apply in the real world, as well as advancing our understanding of biological processes.

The new projects will give the researchers involved access to complementary expertise and skills and will help develop the field of Systems Biology by coordinating BBSRC and ANR resources.

Mr Steve Visscher, BBSRC Interim Chief Executive, said: “Systems Biology holds great promise for delivering real, practical advances in healthcare, biotechnology and environmental research much faster than traditional biology. Collaborative initiatives with international partners enable us to increase the impact of our funding and the impact of the research being done by our scientists.

“We have been pleased to see that not only has the partnership between BBSRC and ANR resulted in a successful initiative but that the range and quality of the projects funded is also broadening the areas being studied by Systems Biology.”

Mrs Jacqueline Lecourtier, ANR General Manager, said: “As a young agency created in 2005, this was the first bilateral call undertaken within the Health & Biology Department. By answering this call, Systems Biology growing communities showed that they were ready to share their views and expertises. Moreover, this initiative allowed BBSRC and ANR to fund high quality and cross-disciplinary proposals, which is one of our missions.

“ANR and BBSRC cooperation was very successful on both levels, management and scientific. Future collaborations involving additional countries are already on their way through the ERANET ERASysBio.”

Source:http://communications.nottingham.ac.uk/News/

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New insights into mushroom-derived drug promising for cancer treatment

A promising cancer drug, first discovered in a mushroom commonly used in Chinese medicine, could be made more effective thanks to researchers who have discovered how the drug works. The research, carried out by The University of Nottingham, was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

In research to be published in the Journal of Biological Chemistry, Dr Cornelia de Moor and her team, in the School of Pharmacy, investigated a drug called cordycepin, which was originally extracted from a rare kind of wild mushroom called cordyceps — a strange parasitic mushroom that grows on caterpillars (see image and notes on use of image) — and is now prepared from a cultivated form.

Dr de Moor said: “Our discovery will open up the possibility of investigating the range of different cancers that could be treated with cordycepin. We have also developed a very effective method that can be used to test new, more efficient or more stable versions of the drug in the Petri dish. This is a great advantage as it will allow us to rule out any non-runners before anyone considers testing them in animals.”

Properties attributed to cordyceps mushroom in Chinese medicine made it interesting to investigate and it has been studied for some time. In fact, the first scientific publication on cordycepin was in 1950. The problem was that although cordycepin was a promising drug, it was quickly degraded in the body. It can now be given with another drug to help combat this, but the side effects of the second drug are a limit to its potential use.

Dr de Moor continued: “Because of technical obstacles and people moving on to other subjects, it’s taken a long time to figure out exactly how cordycepin works on cells. With this knowledge, it will be possible to predict what types of cancers might be sensitive and what other cancer drugs it may effectively combine with. It could also lay the groundwork for the design of new cancer drugs that work on the same principle.”

The team has observed two effects on the cells: at a low dose cordycepin inhibits the uncontrolled growth and division of the cells and at high doses it stops cells from sticking together, which also inhibits growth. Both of these effects probably have the same underlying mechanism, which is that cordycepin interferes with how cells make proteins. At low doses cordycepin interferes with the production of mRNA, the molecule that gives instructions on how to assemble a protein. And at higher doses it has a direct impact on the making of proteins.

Professor Janet Allen, BBSRC Director of Research, said: “Research to understand the underlying bioscience of a problem is always important. This project shows that we can always return to asking questions about the fundamental biology of something in order to refine the solution or resolve unanswered questions. The knowledge generated by this research demonstrates the mechanisms of drug action and could have an impact on one of the most important challenges to health.”

An image of cordyceps mushroom growing on a moth pupa is at: http://www.bbsrc.ac.uk/media/releases/2009/091223-new-insights-mushroom-derived-drug-for-cancer.html.  Please note that you are permitted to use this image to accompany this story only. Additional usage is not permitted under the associated licence.

The research is due to be published in The Journal of Biological Chemistry and is available via early online publication at: http://www.jbc.org/cgi/doi/10.1074/jbc.M109.071159

Source:http://communications.nottingham.ac.uk/News/

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