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3D hi-res bone scanner study helps osteoporosis sufferers
The Evelyn Trust funded the country's first 3D high resolution Xtreme bone scanner, in a collaboration between Ken Poole, based in the NIHR Cambridge Biomedical Research Centre musculoskeletal theme, and Kate Ward of the nearby MRC Human Nutrition Research laboratory. In addition, the NIHR Cambridge BRC funded both Paul Mayhew (a researcher with skills in advance bone image analysis) and a linked Xtreme computer at Addenbrooke's Hospital to analyse the 3D images.
3D high resolution Xtreme bone scanner
Alongside the University Engineering for Clinical Practice team of Graham Treece and Andrew Gee, they were then able to study women suffering from severe osteoporosis and discover exactly where bone was regenerated in response to bone-stimulating therapy, thanks to grant funding from Arthritis Research UK. The osteoporotic women generated new bone at several of the commonest sites of fracture, which is good news. The team now aim to discover the precise effects of targeted exercise on bone health, and to study the spine, a common site of osteoporotic fracture.
Siblings' brain scans could hold the key to drug addiction
Researchers funded by the Medical Research Council (MRC) at the University of Cambridge have identified a brain abnormality which is found in drug-dependent individuals as well as their siblings who have had no history of drug addiction. The brain abnormality identified by researchers makes it more difficult for individuals to exercise self-control. This research will help understanding about why some people with a family history of drug abuse are at a higher risk of addiction than others. Led by Dr Karen Ersche, the researchers scanned the brains of 50 pairs of brothers and sisters, of whom one was dependent on cocaine while the other did not abuse drugs or alcohol. Their brains were compared with those of 50 unrelated healthy volunteers who had no personal or family history of drug addiction.
The researchers found that both drug-dependent and their non-dependent siblings shared the same abnormality in the parts of the brain associated with how we control our behaviour known as the fronto-striatal systems. This kind of abnormality is typically seen in people who struggle with drug addiction.
Dr Ersche commented: 'It has long been known that not everyone who takes drugs becomes addicted, and that people at risk for drug dependence typically have deficits in self-control. Our findings now shed light on why the risk for becoming addicted to drugs is increased in people with a family history of drug or alcohol dependence: parts of their brain underlying self-control abilities work less efficiently.' The next step will be to explore how siblings who don't take drugs manage to overcome their brain abnormality in their daily life.
The findings are published in Science.
For more information about this research go to www.psychiatry.cam.ac.uk.uk/addiction
7 February 2012
Cambridge scientists identify the first patient with a thyroid receptor alpha defect
26 January 2012
Researchers from the Cambridge BRC have described the first person with a defect in the thyroid hormone receptor alpha gene (THRA). The findings boost our understanding of the relative roles of alpha and beta thyroid receptors in different tissues, and should help inform the development of drugs specific to each receptor type.
The team, which included Professors Krishna Chatterjee and Sadaf Farooqi from the Diabetes, Obesity, Metabolism and Endocrinology Theme, studied a six-year-old girl with classical signs of low levels of thyroid hormone (hypothyroidism), including delayed growth and development. Unexpectedly, she had near-normal circulating levels of thyroid hormone.
The researchers sequenced the patient’s DNA and identified a de novo mutation (not seen in either parent) in THRA. By computer modelling the corresponding protein structure, they found that this mutation – a change from one amino acid to another at position 403 – caused the receptor to be shortened. This, in turn, means that an inhibitor of the receptor stays bound to it, leaving the receptor permanently ‘off’ and unable to bind thyroid hormone.
On why the patient’s hormone levels were not more deranged, Prof Chatterjee says, “Our observations support the notion that marked hypothyroidism in selected tissues can be present, even when only small changes in circulating thyroid hormone levels are seen, reflecting the divergent roles of alpha and beta receptors.”
This work is published in the following article:
Bochukova E et al. A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012;366(3):243-9.
Reprogrammed oestrogen binding linked to more aggressive breast cancer
4 January 2012
SCIENTISTS based at Cancer Research UK’s Cambridge Research Institute have discovered how receptors for the female sex hormone oestrogen attach to a different part of the DNA in breast cancer patients who are more likely to relapse, according to a study published in Nature on 4th January*.
Crucially, they also found that within these more aggressive breast cancers, the oestrogen receptor (ER) was being ‘redirected’ to a different part of the genome by a protein called FOXA1. So drugs that specifically block FOXA1 could help treat patients who do not respond to conventional hormone treatments, such as tamoxifen.
The researchers used state of the art technology, called ChIP sequencing, to analyse ER-genome interactions in frozen breast tumour samples** and create a map of all of the sites in the human genome where ER attaches itself to the DNA and switches on particular genes.
This map was used to compare where in the genome ER attached in tumours from people that responded well to treatment, versus those that went on to relapse or were resistant to treatment from the start.
This revealed almost 500 contact points that were common across all the samples analysed, but also a distinct set of contact points specific to patients with different clinical outcomes – of which 599 were associated with good response to treatment and 1,192 with poor response.
Studying patterns of gene activity in these two areas of the genome allowed the researchers to identify a subset of genes that are more active in tumours that return and spread.
Cancer Research UK’s Dr Jason Carroll, who jointly led the study with Professor Carlos Caldas, said: “These findings suggest that ER binds to different regions of the genome DNA in breast cancer patients that respond to treatment, compared to those that relapse and whose cancer spreads.
“We know from previous studies involving breast cancer cells growing in the lab that a protein called FOXA1 is needed for oestrogen receptors to interact with the DNA and switch on genes that fuel cancer growth. But this is the first time we’ve examined frozen tumour samples and shown that FOXA1 redirects ER to different locations within the DNA in patients with different outcomes. This switches on different sets of genes, which in turn affect the outcome of the patient. We now hope to develop ways of blocking FOXA1 to help treat patients who no longer respond to standard treatments.”
Carlos Caldas, Professor of Cancer Medicine at the Department of Oncology at the University of Cambridge and the Cancer Research UK Cambridge Research Institute said: “Some breast cancers are treated with hormone treatments, such as tamoxifen, which work by blocking oestrogen receptors. But we know that about a third of patients either fail to respond to this type of treatment, or go on to relapse at a later date.
“Understanding the genetic differences that determine who will or won’t respond to a given treatment is a vital step in being able to choose the right drugs for individual patients. The next step will be to see if these findings can be repeated in larger groups of patients.”
* Ross-Innes et al., Differential oestrogen receptor binding is associated with clinical outcome in breast cancer (2011), Nature, DOI: 10.1038/nature10730.
** Tumour samples were obtained with support from NIHR Cambridge Biomedical Research Centre and Cancer Research UK’s Cambridge Experimental Cancer Medicine Centre.
About the Cambridge Research Institute
The Cancer Research UK Cambridge Research Institute is a major new research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. The Institute is a unique partnership between the University of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge University, Cancer Research UK, The Atlantic Philanthropies and a range of other donors. For more information visit www.cambridgecancer.org.uk
About Cancer Research UK
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org
International recognition for BRC Scientific Director
Professor Stephen O'Rahilly, Scientific Director of the Cambridge BRC, has been elected as a Foreign Associate of the National Academy of Sciences of the United States of America. The National Academy is the USA's premier scientific academy. Each year it elects 72 new members and 18 Foreign Associates from all scientific disciplines in recognition of their distinguished and continuing achievements in original research. Professor O'Rahilly is distinguished for his research in metabolic and endocrine disease and for his leadership in clinical science.
David Ron, Professor of Cellular Pathophysiology and Clinical Biochemistry, has been selected to present the 2011 Edwin B. Astwood Award Lecture at the 2011 Annual Meeting of the US Endocrine Society. This is awarded in recognition of Prof Ron's outstanding research in endocrinology. Professor Ron is an international authority on endoplasmic reticulum (ER) stress. His research programme involves the development of novel therapeutic agents designed to modify ER stress to ameliorate metabolic disease.
Establishment of new 4 Year PhD Programme
19 October 2011
A new BRC funded 4 Year PhD Programme has been established. The aim of this programme is to attract students with a mathematical, chemistry, biological or physical sciences background into biomedical research.
The research themes of the NIHR Biomedical Research Centre (BRC) are Cancer, Diabetes, Obesity and Metabolic Disorders, Neuroscience, Transplantation, Cardiovascular Medicine, Infection and Immunity, Genetics and Genomics, Mental Health, Women's Health, Musculoskeletal Disorders and Imaging.
The initial year of training will include either a taught MPhil (in either Epidemiology, Public Health or Computational Biology) or an MRes made up of mini projects as described above. Students then select an area for in-depth doctoral study in years 2-4. This exciting new scheme will include studentships that involve collaboration between departments covering these themes, the Institute of Public Health and University of Cambridge faculties of biological sciences and physical sciences.
Further details available from http://www.cimr.cam.ac.uk/study/brc/index.html
Young Investigator Award
4 September 2011
The American Society of Bone and Mineral Research (ASBMR) has awarded ARC Clinical Scientist Fellow, Ken Poole, a young investigator award for his work on hip fractures. Dr Poole said: "This was a team achievement - only possible because of the Engineering for Clinical Practice initiative which is supported locally by the Evelyn Trust, the NIHR BRC and nationally by my Arthritis Research UK award". At the ASBMR's San Diego meeting the Japanese Bone Society also invited Dr Poole as one of the best four oral presentations to expand their findings at a special event in Tokyo in February 2011.
In addition, the Evelyn Trust has awarded Tom Turmezei, a member of Dr Poole's group, an ACF Clinical fellowship to apply these techniques further in osteoarthritis.
Synopsis: By 2050, the number of people suffering a hip fracture will exceed 6 million per year. Here we report a remarkable discovery which will substantially alter the way that clinicians and scientists think about fragility fractures of the hip. We have discovered a thumbnail-sized patch of focal osteoporosis in the hips of older women with femoral neck fracture, distinct from the generalised thinning and porosity reported previously. What is more, the focal osteoporosis coincides with the part of the femur that cracks during a fracture. These discoveries were made in patients using a beautiful new way of examining the skeleton in life, 3D cortical bone mapping from CT scans. We previously used the technique in severely osteoporotic women to demonstrate bone regeneration in critical parts of the femur in response to bone-active therapy.
News from the Cancer theme
Bertie Gottgens: Blood cancer research in Cambridge was recognised last year as a centre of national excellence. Read more at http://www.beatbloodcancers.org/news-media/cambridge-unveiled-centre-excellence-blood-cancer-research
Upper GI research lead Rebecca Fitzgerald and her team have just been selected as the finalist in the early cancer detection of the NHS innovation awards for the Cytosponge. The overall winner will be announced in the next few weeks.
Official Launch of the Cambridge Pancreatic Cancer Centre: http://www.oncology.cam.ac.uk/home/news_2011.html#CPCC
http://www.bbc.co.uk/news/uk-england-cambridgeshire-12907946
Highlights
Clinical Trials and Lung (Tim Eisen)
The Cambridge Cancer Trials Centre is a collaboration between Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK and the University of Cambridge.
