BioMed Central Blog
Renal and bladder cancer: current trends and controversies
Urology and oncology specialists came together in London on the 26th–27th January to discuss new developments and controversial topics at the 3rd National Renal and Bladder Cancer conference. Around 80 specialists attended each day including surgeons, oncologists, radiologists and scientists.
An important theme linking many speakers’ presentations across both days was personalized cancer treatment, and how knowing more about patients’ individual genetic information will lead to tailored treatment and improved patient care. Mr Tim O’Brien from Guy’s and St Thomas’ NHS Foundation Trust opened discussions with an interesting presentation about how patient care is currently managed for renal cancer, and how we should move towards personalized medicine in the future. Dr Athena Matakidou from the Cancer Research UK Cambridge Institute continued with this theme by describing recent efforts to sequence the genes involved in renal cancer. In addition, Dr Nav Vasudev discussed CAGEKID, an internationally collaborative project aimed at clinically characterizing the genetic changes that occur in patients with renal cancer, which should lead to more individualized treatment in the future.
Prof Margaret Knowles kicked off the sessions on the second day with a discussion of the genetic biomarkers for bladder cancer and how they could be applied to predict patients’ responses to different treatments. Dr Tom Powles summarized recent and ongoing clinical trials for bladder cancer, highlighting the unique LaMB trial, which is the first to take into account patients’ genetic information for bladder cancer treatment.
A controversial topic in bladder cancer treatment is whether surgery or radiotherapy should be used as first-line therapy; Prof Nick James outlined the advantages and disadvantages of each approach, and discussed the importance of selecting patients who are likely to respond well to radiotherapy. An interesting debate involving many specialists followed, with some preferring surgery and others believing that radiotherapy should be given in the first instance. Mr Shamin Khan described a recent advance in surgery for bladder cancer, robotic cystectomy, which helps to reduce patient recovery time after the operation and could soon be used in hospitals across the country.
The conference highlighted how recent progress in identifying genes associated with both renal and bladder cancer will be translated into personalized treatment in the future. We should look out for exciting developments in validating genetic and protein biomarkers in the clinic, and eagerly await the results of the landmark LaMB trial.
Posted by Claire Tree-Booker at 10:32 Comments (0)
Norwegian attacks July 2011: The emergency medical service response report
The two horrific attacks on 22nd July 2011 of the car bombing at the Government district in Oslo, and the shooting of participants at a national Labour Party youth camp on nearby Utøya island, saw one of the worst massacres Norway has faced. The devastating actions of a single perpetrator left a total of 77 people dead, and a nation questioning the motives of such actions. The scale of these two attacks was unprecedented in Norway, and understandably required an enormous amount of effort and resources from the police and emergency medical service (EMS). Six months on, a study describing the immediate prehospital EMS response to these incidents and a corresponding commentary by Prof David Lockey have been published in Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine.
The Norwegian study objectively describes the two events separately, giving details of emergency medical service response times to the scene, triage procedures and scene descriptions. Co-author Dr Stephen Sollid, Consultant Anaesthesiologist at Oslo University Hospital, and Medical Advisor at the Norwegian Air Ambulance Foundation explained,
“It was quite impressive to experience the way personnel from different systems were able to establish a working casualty clearing system. This was probably in the spirit of everyone pulling their weight under the given circumstances, but it is an experience that will certainly stay with those of us that took part in the rescue work that day and should inspire - at least - other EMS systems in Norway”.
In the initial analysis following the attacks, the police were criticized for their response time to Utøya island, and the transport issues faced with lack of helicopters and boats. The Norwegian air ambulance service were able to provide sufficient support for the pre-hospital medical services, and with approximately 60 flights logged, it is clear that availability of these resources is paramount for emergency incidences.
The report will allow other EMS services to analyse and provide improved emergency responses to future incidents. Unfortunately it is near impossible to predict when such attacks will next occur, and a state of preparedness is all that is possible.
Posted by Shivani Patel at 15:27 Comments (0)
Ovarian cancer is the fifth most common cancer affecting women in the UK, and 6,500 women are diagnosed every year. Cisplatin is commonly used to treat ovarian cancer, but it is associated with side effects in some people, and some types of this cancer are resistant to cisplatin treatment. There is thus a pressing need for the development of new drugs that are effective against ovarian cancer in people who are less responsive to cisplatin.
The novel anti-cancer drug Diindolylmethane (DIM) has previously been shown to prevent the growth of ovarian cancer cells, without affecting normal cells. In a new study published by BMC Medicine, Kandala and Srivastava shed light on the mechanism by which DIM affects ovarian cancer cells. The authors show that DIM works by blocking production of the transcription factor STAT3, whose normal role is in cell growth and division. STAT3 is present at abnormally high levels in many types of cancer, and has been implicated in cisplatin resistance. They found that DIM blocks STAT3 activation by the immune system messenger interleukin 6 (IL-6), and also reduces the amount of IL-6 in ovarian cancer cells.
Importantly, Kandala and Srivastava also showed that DIM enhanced the anti-cancer effects of cisplatin in both human ovarian cancer cells and in mice, where a combination of both drugs reduced tumour growth by an extra 50% compared with cisplatin alone. DIM is an exciting potential future therapy for ovarian cancer, which could overcome the problems with cisplatin resistance in some women.
Posted by Claire Tree-Booker at 10:10 Comments (0)
Global lipid profiling provides clues to schizophrenia pathogenesis
Recent research published in Genome Medicine presents a comprehensive, global view of lipid abnormalities associated with schizophrenia, providing new pathophysiological insights into the disorder.
Following on from their earlier work published in Genome Medicine, which reported metabolites that differentiate schizophrenia from related disorders, Matej Orešič and colleagues from the VTT Technical Research Centre of Finland used metabolomics (a high-throughput method for detecting small metabolites) to determine the lipid profile of people with schizophrenia. In psychiatric research, several theories have been proposed to explain how brain function may be altered by changes in lipid composition, and this study sought to understand which specific pathways are affected in schizophrenia.
The group analyzed the lipid content of serum samples taken from monozygotic twins that are discordant for schizophrenia i.e. only one twin in each pair is affected. The advantage of this unique study design is that discordant twins are an ideal population for investigating the contribution of genetic factors to disease etiology. Age and gender matched healthy twin pairs were included as controls, and neurocognitive and magnetic resonance image data were available for selected twins.
Compared with healthy controls, individuals with schizophrenia had higher triglyceride levels and showed signs of insulin resistance, in line with earlier reports. However, the patients’ unaffected co-twins were also found to be insulin resistant, providing new evidence that this could be an inherited trait associated with predisposition to schizophrenia. Affected twins also had lower levels of phospholipid derivatives called lysophosphatidylcholines (lysoPCs). This change, which was not observed in healthy co-twins or controls, correlated with decreased cognitive speed. Because lysoPCs are involved in blood-brain barrier transport of polyunsaturated fatty acids, the authors conclude that a drop in their levels may be responsible for changes in neurotransmission and weaker cognitive performance. They also propose that lysoPC deficiency could make schizophrenia patients more susceptible to infections. These findings pave the way for further research into the role of lysoPCs in schizophrenia.
The mechanistic insights reported by Orešič and colleagues may be useful for the discovery of new drug targets for schizophrenia. In addition, the work demonstrates how a discordant twin study design can successfully uncouple genetic and environmental factors, allowing disease-specific inherited traits to be accurately defined.
Posted by Paraminder Dhillon at 13:49 Comments (0)
Therapy for Alzheimer's disease may cause side effects
Alzheimer’s disease (AD) affects an increasing number of people and research continues to develop new treatments, many of which are currently undergoing clinical trials. However, new research suggests that one such treatment using drugs to inhibit BACE1 may cause unwanted side effects.
Robert Vassar, lead author of the study recently published in Molecular Neurodegeneration, says “We are in desperate need of something that can treat or prevent Alzheimer’s disease, but at the same time we have to be on the lookout”. Vassar’s recent study is the first to identify a role of BACE1 in axon guidance, or the process by which axons connect and ensure communication between neurons. Defects result when the process of connecting axons goes awry.
Simply put, such defects in brain wiring can be likened to defects in the wiring of a house. “You have to wire correctly in order to get electricity into the house to turn on the lights, but if the wiring is not correct the lights won’t function,” Vassar said. “In humans, the brain automatically accomplishes correct wiring through axon guidance.”
However, BACE1 inhibitors may impede this normal process as evidenced by the researchers’ discovery of wiring mistakes in the brains of animal models. By using the olfactory system as a model of axon guidance, the researchers showed that when BACE1 is genetically removed from mice, axons of olfactory sensory neurons were not able to wire properly to the olfactory bulb of the brain. Such findings demonstrate the role of BACE1 in axon guidance, and how inhibiting BACE1 “could cause unwanted side effects or defects in the wiring of the brain or peripheral nervous system.”
While researchers speculate that there may be other neuron systems that require the activity of BACE1 for proper wiring, understanding the molecular basis of new physiological functions for BACE1 may eventually aid in the development of therapies with workarounds for side effects.
Posted by Sian Jones at 12:32 Comments (0)
Emergency medicine specialists convene in London
This week, BMC Medicine attended the 4th Annual Emergency Medicine conference in London, where key themes and hot topics in the field of emergency medicine were discussed. The meeting was attended by around 70 delegates, including consultants in emergency and acute medicine, paramedics, and specialists in trauma and orthopedics.
The presentations were thematically diverse and covered all aspects of emergency medicine. Popular topics included simulation training in a pre-hospital environment, as well as recognition and clinical management of novel recreational drugs - the so called ‘legal-highs’.
Changes afoot in terms of ambulance commissioning in the UK were debated, with an excellent presentation by Neil Kennett-Brown, the director of London Ambulance Service Commissioning, who discussed the background to these changes in care pathways, which aim to increase emergency department efficiency.
Of particular interest given the forthcoming Olympics in London was a session focused on sports medicine, led by Laurence Gant who is a Consultant and Clinical Director in Emergency Medicine at Homerton Hospital. Dr Gant, who is involved in the planning of medical care for athletes and spectators for the London Olympics, highlighted the challenges and solutions in organizing a large scale international event. Mike Carmont, a consultant trauma and orthopedic surgeon, discussed emergency assessment of sports injuries, and Jonathan Hanson provided an in-depth presentation on the causes, management and prevention of sudden cardiac arrest in athletes.
The core themes discussed at this conference will provide researchers and clinicians with deeper background knowledge and practical skills to advance the field of emergency medicine.
Posted by Lin Lee at 16:33 Comments (0)
The December issue of Genome Medicine highlights the growing potential of genomics research for the development of personalized medicine, particularly for improving the effectiveness of anticancer therapeutics.
In a Research article, Matthias Schwab and colleagues demonstrate for the first time that decreased expression of an organic cation transporter SLC22A1 in hepatocellular carcinoma (liver cancer) correlates with increased methylation of the encoding gene. Their findings suggest that aberrant DNA methylation could be used for early detection of the disease, and that demethylating agents could be used for treatment. 
Continuing the theme of cancer therapy, Ram Ganapathi and Ronald Bukowski discuss recent progress in predicting response or toxicity following sunitinib treatment in patients with renal cell cancer, and make suggestions for improving future trials.
In a report on the 2011 Wellcome Trust Pharmacogenomics and Personalized Medicine meeting, Mia Wadelius and Ana Alfirevic highlight other examples of pharmacogenomics research and its increasing presence in the clinic. This report has already been highly accessed, emphasizing the growing interest in this area.
The importance of post-genomic technologies is described in a Research Highlight from Frank Kooy and colleagues, which focuses on a novel metabolomics approach to understanding Fragile X syndrome. Our upcoming special issue on “Disease Metabolomics” will expand on this theme and provide insights from experts in this field. 
The issue wraps up with two Reviews on vastly different areas of research. The first, from Leonard Zon and colleagues, discusses recent advances in hematopoiesis research that are facilitated by the zebrafish model.
Finally, Melanie Myers addresses the important issue of direct-to-consumer (DTC) genetic testing and advertising in terms of the impact on health care providers.
Genome Medicine wishes you a happy new year and looks forward to bringing you the best in genomic medicine in 2012. Look out for our upcoming Editorial to read our Section Editors’ views on how the field had changed over the past year.
Posted by Paraminder Dhillon at 15:17 Comments (0)
The field of medicine as a whole has progressed
substantially in recent years owing to advances in technology as well as
improved diagnostic techniques and therapies. In particular, progress in
neuroimaging and other neurophysiological techniques, developments in
behavioural sciences and psychotherapies, and developments in psychiatric
genetics have substantially expanded our knowledge of mental illnesses. As a
result, the profession and practice of psychiatry is evolving, and so there is
a need to review how current practices should be revised, updated and
monitored. This is reflected by the imminent release of the revised Diagnostic
and Statistical Manual (DSM-5) by the American Psychiatric Association, which is expected to improve the clinical
utility of the manual and also ensure more consistency in how psychiatric
disorders are classified and diagnosed.
However,
other factors also affect the scope and conduct
of the psychiatric field. Socio-cultural and economic forces have an influence,
as the structure of societies are changing worldwide. The profession of
psychiatry is becoming increasingly globalized and continuously confronts new
challenges, as international ethnic, religious and political beliefs and
behaviours are becoming more prominant.
In the cross-journal thematic series ‘Towards a new psychiatry: Philosophical and ethical issues in classification, diagnosis and care’, edited by Prof James Giordano (Editor-in-Chief of Philosophy, Ethics, and Humanities in Medicine), the issues arising from these socio-cultural
changes and scientific advances are explored. The main themes and aims of the
thematic series, as well as key papers that the series has been launched with,
are discussed in the editorial, and Prof Giordano also comments on the impact of
the changes in psychiatry in his blog. The thematic issue runs until December 2012, and submissions addressing these themes are invited to the following journals for inclusion: BMC Medicine; BMC Medical Ethics; BMC Psychiatry; BMC Neuroscience; BMC Neurology; Genome Medicine and Philosophy, Ethics, and Humanities in Medicine.
Posted by Liz Hoffman at 14:44 Comments (0)
Stem Cell Educator for diabetes
Type 1 diabetes is a form of diabetes mellitus that is caused by the body’s own immune system attacking its pancreatic islet β cells. These cells would normally produce insulin, which regulates glucose metabolism. Therefore, type 1 diabetic patients require life-long daily insulin injections in order to avoid health complications such as atherosclerosis, neuropathy and kidney disease.
Affecting around 10% of all diabetes patients, type 1 diabetes is far less common than type 2 diabetes, but its incidence has doubled in the past 20 years. This, in combination with the current, often inconvenient management of type 1 diabetes, has led researchers to develop alternative treatment strategies.
This resulted in regeneration of islet β cells that were then able to produce insulin again, so that 12 weeks after treatment all the patients who received the therapy had improved β cell function. This continued to improve and was maintained to the end of the study. Interestingly, this also meant that the daily dose of insulin required to maintain patients’ blood glucose levels could be reduced.
These remarkable results may provide a new approach to overcome the autoimmunity underlying type 1 diabetes, and may have important implications for other autoimmune and inflammation-related diseases.
Posted by Lin Lee at 17:46 Comments (0)
DNA methylation of drug transporter gene might explain chemoresistance in liver cancer
Hepatocellular carcinoma is the third highest cause of cancer-related
death world-wide. Although several treatments are available – and many more are
undergoing clinical trials – drug resistance is a problem in some cases.
In the latest issue of Genome Medicine, Matthias Schwab and colleagues show for the first time that there is a link between the level of expression of the chemotherapy drug transporter SLC22A and DNA methylation. This finding might explain reduced drug responses in liver cancer and provide a new approach for treating patients.
The team looked at the methylation patterns in the 5' end of
three genes encoding organic cation transporters (SLC22A1, SLC22A2 and SLC22A3)
in liver samples taken from people with hepatocellular carcinoma and compared
them with normal livers. A
state-of-the-art mass spectrometry approach was used to examine DNA
methylation.
They found that decreased expression of SLC22A1 in hepatocellular carcinoma correlated with increased methylation of the SLC22A1 gene, and suggests that SLC22A1 is epigenetically regulated.
The good news is that epigenetic modifications are reversible and so pretreatment with a chemical to reduce methylation might result in improved chemotherapy.
Posted by Maria Hodges at 13:53 Comments (0)
"Launched in 2003 with financial backing from the Bill and Melinda
Gates Foundation, Avahan is the world’s largest HIV prevention programme.
‘Learning
from large scale prevention efforts – findings from Avahan’ is a newly
published supplement in BMC Public Health, Edited by Lalit Dandona and
Eric Benotsch, that documents the role of the initiative in the fight against
HIV/AIDS in India.
Avahan involved 134 local non-governmental organizations that implemented the project in 6 regions of India, targeting individuals most at risk of contracting HIV. This included female sex workers and their clients, men who have sex with men, truck drivers and injecting drug users. The programme of prevention was tailored to the specific needs of the population in India and implemented a number of evidence-based interventions: peer-led outreach and behavior change communication; services for STI testing and care and condom promotion and distribution; and harm reduction for intravenous drug users.
Of paramount importance to the success of Avahan was creating an enabling environment in the communities where the programme operated; for example, police harassment or violence against women, which might discourage uptake of services or use of condoms was addressed, a cash transfer system with cell phones for the sex workers was implemented, and shower facilities for were truck drivers built. Thus Avahan employed a combination of evidence-based and common sense interventions, and to great effect.
Garung et al report that more than 331,000 female sex workers, 89,000 men who have sex with men and transgenders, and 10,000 injecting drug users visited sexually transmitted infection clinics through Avahan between 2005 and 2009, and the rate of diagnosis of sexually transmitted infections decreased substantially over this period. Overall it has been estimated that Avahan averted more than 100,000 new HIV infections in a 5 years period between 2003 and 2008.
As Bea Vuylsteke and Marie Laga state in their Commentary: “For the first time, it has been shown, with a prospective design, that a large scale targeted HIV prevention programme, including standardized programme packages reinforced with community mobilization approaches, is possible and works.”
Posted by Ian Ward at 11:16 Comments (1)
Simple blood test for bowel cancer
Bowel cancer (also known as colorectal cancer or colon cancer) is the third most common cancer, and is responsible for over 16 000 deaths in the UK every year. The sooner bowel cancer is detected, the more easily it can be treated; approximately 90% of people survive for over 5 years if diagnosed at the earliest stage (known as Dukes A).
Screening programmes can identify people with the disease before any symptoms develop and so are important for successful treatment. However, compliance with screening, which typically involves a colonoscopy, is a problem. Less invasive procedures for bowel cancer detection are likely to improve compliance and could lead to earlier diagnosis and treatment.
Detection of bowel cancer biomarkers by a blood test is an attractive prospect; a blood test is less invasive than a colonoscopy, and can be easily carried out at GP surgeries and many healthcare systems already offer routine blood tests. In 2008, three blood-based biomarkers for bowel cancer were identified, including septin 9 (SEPT9) methylated DNA.
In a recent study published by BMC Medicine as part of the Clinical Biomarkers thematic series, Jorga Warren and 
colleagues describe a blood-based bowel cancer screening test for SEPT9 methylated DNA with better sensitivity and specificity than previous tests for this biomarker. The study showed that 90% of all bowel cancers from different locations and stages can be detected by the SEPT9 blood test. Detection of this biomarker in the blood could provide an alternative to colonoscopy for screening, leading to improved compliance and further reductions in deaths from bowel cancer.
Posted by Lin Lee at 16:21 Comments (0)
November highlights from Genome Medicine: miRNA as a biomarker, RNA-seq, diabetes and more
November’s
issue of Genome Medicine reflects the
excitement in the field about the potential for RNA to act as a biomarker for
disease and to help researchers unravel the underlying disease mechanism.
MicroRNAs, which
are short RNAs of around 22 nucleotides, are attracting a lot of interest for
detecting and predicting the outcome of a disease. In a Research Highlight,
Florian Kuchenbauer and colleagues reflect on the recent finding that microRNAs
are expressed at different levels in blood in different diseases, which could
lead to blood-based diagnosis of disease. This issue also features a Research
Article by Rotem Ben-Hamo and Sol Efroni, which indicates a role for
microRNA hsa-miR-9, along with the p38 network, in predicting the prognosis of patients with the brain cancer
glioblastoma multiforme (see blog to find out more).
The other Research Highlight this month examines a new assay, termed CaptureSeq, that enriches low-level RNA transcripts for high-throughput RNA sequencing (RNA-Seq).
Recently, Genome Medicine has highlighted the increasing clinical impact of pharmacogenomic research, and in a Review Article by Jose Florez and Chunmei Huang the authors look at insights emerging from the pharmacogenetic and pharmacogenomic studies of type 2 diabetes.
Stuart Orkin, Guest Editor of our Focus on Stem Cells, and Jonghwan Kim have provided a Review on embryonic stem cell-specific
signatures in cancer.
Meeting
reports in the journal are proving to be popular, and this month is no
exception. Have a look at the Report of the Wellcome Trust meeting on Epigenomics of common disease and the Cold Spring Harbor Laboratory Report on Personal Genomes.
If you missed last month’s issue, you can look at it here. Elad Ziv and colleagues’ Research Article attracted a lot of interest, as the first report that doctors do change prescriptions for patients with breast cancer when they receive genotyping information. David Gurwitz and Jeantine Lunshof discuss this study and the implications for personalized medicine in an associated Research Highlight.
Other highly accessed articles from last month include Alan Wright’s Report on the Wellcome Trust conference on the Genomics of Common Diseases, Huck-Hui Ng’s review article on transcriptomic analysis of stem cells, and Wyeth Wasserman’s Review of the methods and software for predicting functional variation within the cis-regulatory sequences.
Posted by Maria Hodges at 16:57 Comments (0)
Group therapy delays progression of dementia
Dementia describes a set of progressive neurodegenerative symptoms resulting in serious impairment of cognitive ability beyond what might be expected from the normal ageing process. Several conditions and diseases may cause dementia, the most common of which is Alzheimer’s disease. Dementia mainly affects people over the age of 65 and the prevalence of this condition in our ageing population is increasing. Estimates suggest a global dementia prevalence of 24.3 million, with 4.6 million new cases of dementia every year. This number is speculated to double every 20 years to 81.1 million cases by 2040. Currently, there are no preventative or curative treatments for dementia, although medications (e.g. acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor blockers) are usually prescribed to treat the behavioural and cognitive symptoms of dementia. There is therefore a real need for further research into the treatment of this debilitating condition.In an article published by BMC Medicine, Elmar Graessel and colleagues, tested the impact of a non-pharmacological intervention on patients from five nursing homes in Bavaria, Germany. All patients suffered from mild to moderate dementia, and maintained their normal treatment and regular activities provided by the nursing home throughout the study. Half of the patients were randomly selected for the therapy sessions
.The intervention had a striking effect. The sessions consisted of participation in two hours of group therapy a day, six days a week, and combined physical activity (including playing sports and balancing exercises), cognitive tasks (such as individual and group puzzles) and active discussion. One year later, those who took part in the intervention were shown to have postponed their decline in cognitive function. In addition, they were able to maintain their ability to carry out daily activities, unlike those who just received usual care. Remarkably, this intervention appears to be as effective as anti-dementia drugs at stabilizing cognitive function. These results may encourage greater social participation and activity within a nursing home environment to stave off the effects of dementia.
Posted by Lin Lee at 16:05 Comments (0)
A transcription network at the core of brain cancer
Research published this week in Genome Medicine provides new insights
into the molecular pathways underlying brain cancer (glioblastoma multiforme). Sol
Efroni and Rotem Ben-Hamo from Bar IIan University in Israel analyzed gene
expression and clinical data for a large number of patients, with the aim of
identifying prognostic biomarkers and new therapeutic targets.
Glioblastoma multiforme is a common, aggressive form of brain cancer associated with extremely low survival rates. The disease is usually fatal even following therapy, highlighting the need for early diagnosis and the development of more effective drug regimes. In this study, Efroni and Ben-Hamo applied a series of computational algorithms to five independent microarray datasets to identify gene expression networks that correlate with poor prognosis. As part of their analysis, data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database and The National Cancer Institute’s Pathway Interaction Database (PID) were merged, representing a uniquely powerful “systems biology” approach to biomarker discovery.
This integrated approach revealed that the expression of one pathway, the p38/MAPK transcription network, significantly affiliates with poor survival. This network was shown to be regulated by a microRNA, hsa-miR-9, implicating another important biomarker for the disease. Interestingly, analysis of DrugBank data showed that patients who had received drugs targeting the p38/MAPK pathway displayed higher survival rates compared with patients who had been treated with other drugs. These results suggest that the p38/MAPK network is critical in glioblastoma multiforme progression and should form the focus of future clinical studies of the disease.
Posted by Paraminder Dhillon at 10:01 Comments (0)