Developed in Canada and conducted by researchers from the University of Ottawa Heart Institute, in partnership with Spartan Bioscience, the world’s first bedside genetic test has received acknowledgment by The Lancet. The article entitled ‘Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial’ reports on the use of a simple cheek swab test, the Spartan RX CYP2C19, performed by nurses at the patient’s bedside. This revolutionary technology allows patients with the genetic variant CYP2C19*2 to be rapidly identified. Cardiac stent patients with this variant are at risk of reacting poorly to standard anti-platelet therapy with Plavix (clopidogrel).
The study demonstrated that tailored drug treatment therapy made possible by genetic testing successfully protected all of the patients with the at-risk genetic variant from subsequent adverse events, while 30 per cent of patients treated with standard therapy did not receive adequate protection. The test is a significant step towards the realisation of personalised medicine.

Scientists from the University of Liverpool’s School of Environmental Sciences are working with computer modelling specialists from C-MMACS in India to predict areas of the country that are at most risk of malaria outbreaks, following changes in monsoon rainfall. The number of heavy rainfall events in India has increased over the past 50 years, but research has tended to focus on the impact this has on agriculture rather than the vector-borne diseases, such as malaria and Japanese encephalitis. The model could help inform early intervention methods to prevent the spread of malaria at key points in the seasonal monsoon cycle, reducing the economic and health impacts of the disease. It is already known that an anomalous season of heavy rainfall, when heat and humidity are high, allows mosquitoes to thrive and spread infection to humans. In order to prepare health services and prevent epidemics there is need for a way of predicting when these events are likely to occur in areas that are not accustomed to annual outbreaks of malaria. C-MMACS is rapidly developing its computer modelling capabilities using technology that can address the impacts of climate variability on agriculture and water systems. This knowledge, together with the Liverpool models of vector-borne diseases, will help develop systems to predict when changes in the monsoonal rain may occur and which areas are most likely to see an increase in malaria.

Fibroid uterine tumours affect an estimated 15 million women in the United States, causing irregular bleeding, anaemia, pain, and infertility. Despite the high prevalence of the tumours, which occur in 60 percent of women by age 45, the molecular cause has been unknown.
New Northwestern Medicine pre-clinical research has for the first time identified the molecular trigger of the tumour — a single stem cell that develops a mutation, starts to grow uncontrollably and activates other cells to join its frenzied expansion.
‘It loses its way and goes wild,’ said Serdar Bulun, MD, the chair of obstetrics and gynaecology at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital. ‘No one knew how these came about before. The stem cells make up only 1.5 percent of the cells in the tumour, yet they are the essential drivers of its growth.’
The stem cell initiating the tumour carries a mutation called MED12. Recently, mutations in the MED12 gene have been reported in the majority of uterine fibroid tissues. Once the mutation kicks off the abnormal expansion, the tumours grow in response to steroid hormones, particularly progesterone.
For the study, researchers examined the behaviour of human fibroid stem cells when grafted into a mouse, a novel model initiated by Northwestern scientist Takeshi Kurita, PhD, a research associate professor of obstetrics and gynaecology. The most important characteristic of fibroid stem cells is their ability to generate tumours. Tumours originating from the fibroid stem cell population grew 10 times larger compared to tumours initiated with the main cell population, suggesting a key role of these tumour stem cells is to initiate and sustain tumour growth.
‘Understanding how this mutation directs the tumor growth gives us a new direction to develop therapies,’ said Bulun, also the George H. Gardner Professor of Clinical Gynecology. University Feinberg School of Medicine

Resistances to drugs are the main reason why breast cancer cannot effectively be fought in many patients. Scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now succeeded in restoring the sensitivity of resistant breast cancer cells to tamoxifen using a tiny RNA molecule. These snippets of RNA repress production of a protein that enhances cancer growth. In tissue samples of breast tumours, the investigators found clues that they also play a clinically relevant role.
Many breast cancer patients are treated with a drug called tamoxifen. The substance blocks the effect of oestrogen and thus suppresses the growth signals of this hormone in cancer cells. When resistance to the drug develops, tumour cells change their growth program: They change their behaviour and shape, become more mobile and also adopt the ability to invade surrounding tissue. Scientists working with PD (Associate Professor) Dr. Stefan Wiemann of the German Cancer Research Center (DKFZ) have now also observed these changes in tamoxifen resistant breast cancer cells.
‘Resistances to drugs are the main reason why therapies fail and disease progresses in many cancers,’ Wiemann explains. ‘We want to understand what goes on in the cells when this happens so we can develop better therapies in the future.’ Wiemann’s co-worker, Dr. Özgür Sahin, suspects that tiny pieces of RNA known as microRNAs play a role in resistance development. ‘These minuscule RNA snippets control many cellular processes by attaching themselves to target gene transcripts and thus repressing protein production.’
By treating breast cancer cells in vitro with regular doses of tamoxifen, Sahin’s team induced resistance of these cells to the drug. As resistance developed, the cancer cells switched to the development program that makes them grow even more invasively and more malignantly. Checking the complete spectrum of microRNAs in the resistant tumour cells, the investigators noticed that production of microRNA 375 was more strongly reduced than others. When they boosted the production of microRNA 375, the cells started responding again to tamoxifen and switched back to their normal growth program. ‘This strongly suggests that a lack of microRNA 375 both increases malignancy and contributes to resistance development,’ says Özgür Sahin.
If microRNA 375 levels are low, breast cancer cells increase the production of metadherin. Apparently, microRNA 375 suppresses the production of this cancer-promoting protein in healthy cells. In patients receiving tamoxifen therapy the team found that high metadherin levels in the cancer cells go along with a high risk of recurrence. This suggests that microRNA 375 and metadherin are involved in the development of resistance to tamoxifen.
‘The analysis of microRNAs in breast cancer has put us on the track of metadherin. We will possibly be able to specifically influence the cancer-promoting properties of this protein in the future,’ says Wiemann describing the goal of further research. The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Researchers in the University of Leicester’s Department of Cell Physiology and Pharmacology have identified a cellular mechanism that could underlie the development of tinnitus following exposure to loud noises. The discovery could lead to novel tinnitus treatments, and investigations into potential drugs to prevent tinnitus are currently underway.
Tinnitus is a sensation of phantom sounds, usually ringing or buzzing, heard in the ears when no external noise is present. It commonly develops after exposure to loud noises (acoustic over-exposure), and scientists have speculated that it results from damage to nerve cells connected to the ears.
Although hearing loss and tinnitus affect around ten percent of the population, there are currently no drugs available to treat or prevent tinnitus.
University of Leicester researcher Dr Martine Hamann, who led the study said: ‘We need to know the implications of acoustic over exposure, not only in terms of hearing loss but also what’s happening in the brain and central nervous system. It’s believed that tinnitus results from changes in excitability in cells in the brain – cells become more reactive, in this case more reactive to an unknown sound.’
Dr Hamann and her team, including PhD student Nadia Pilati, looked at cells in an area of the brain called the dorsal cochlear nucleus – the relay carrying signals from nerve cells in the ear to the parts of the brain that decode and make sense of sounds. Following exposure to loud noises, some of the nerve cells (neurons) in the dorsal cochlear nucleus start to fire erratically, and this uncontrolled activity eventually leads to tinnitus.
Dr Hamann said ‘We showed that exposure to loud sound triggers hearing loss a few days after the exposure to the sound. It also triggers this uncontrolled activity in the neurons of the dorsal cochlear nucleus. This is all happening very quickly, in a matter of days’
In a key breakthrough in collaboration with GSK who sponsored Dr Pilati’s PhD, the team also discovered the specific cellular mechanism that leads to the neurons’ over-activity. Malfunctions in specific potassium channels that help regulate the nerve cell’s electrical activity mean the neurons cannot return to an equilibrium resting state.
Ordinarily, these cells only fire regularly and therefore regularly return to a rest state. However, if the potassium channels are not working properly, the cells cannot return to a rest state and instead fire continuously in random bursts, creating the sensation of constant noise when none exists.
Dr Hamann explained: ‘In normal conditions the channel helps to drag down the cellular electrical activity to its resting state and this allows the cell to function with a regular pattern. After exposure to loud sound, the channel is functioning less and therefore the cell is constantly active, being unable to reach its resting state and displaying those irregular bursts.’
Although many researchers have investigated the mechanisms underlying tinnitus, this is the first time that cellular bursting activity has been characterised and linked to specific potassium channels. Identifying the potassium channels involved in the early stages of tinnitus opens up new possibilities for preventing tinnitus with early drug treatments.
Dr Hamann’s team is currently investigating potential drugs that could regulate the damaged cells, preventing their erratic firing and returning them to a resting state. If suitable drug compounds are discovered, they could be given to patients who have been exposed to loud noises to protect them against the onset of tinnitus. University of Leicester