Atrial fibrillation (AF) is a heart condition that causes an irregular, and often rapid, heart rate. It increases the risk of developing strokes, heart failure, and even dementia. Although it can be associated with aging, high blood pressure, diabetes, heart valve problems, etc, about one-third of patients with AF have no symptoms until they suffer a stroke. Therefore, a means of identifying or predicting AF with the aim of starting preventative therapy is highly desirable.
AF is associated with several factors that maintain its progression, including inflammation, electrical disturbances, and structural changes in the heart’s upper chambers (the atria). Moreover, several different short sequences of RNA known as microRNAs (miRNAs) have been linked with AF pathology. miRNAs control gene expression after the transcription stage, and have been suggested as possible markers for some cardiovascular diseases because of their stability in the bloodstream. However, it remains unknown whether the miRNAs shown to be related to AF are suitable as predictive biomarkers of disease.
A team of researchers from Tokyo Medical and Dental University (TMDU) addressed this issue by comparing miRNA expression in AF patients and healthy controls, and between control mice and those with a similar abnormal heart rhythm to AF. They showed that four miRNAs not previously associated with AF were significantly upregulated in the serum of AF patients and diseased mice, indicating their potential use as AF biomarkers. The study results were recently published in Circulation Journal.
Initially, human serum and mouse atrial tissue were screened for 733 and 672 miRNAs, respectively. These were eventually narrowed down to four by excluding non-detectable and non-specific miRNAs, and focusing on the quantification of their expression.
“One of the miRNAs, miR-214-3p, is implicated in inflammation, so we wondered whether this might be the underlying mechanism of miRNA-induced AF pathology,” first author Yu Natsume says. “We compared miRNA expression with levels of a serum inflammatory factor but found no correlation suggestive of an association.”
Statistical analysis of diagnostic ability showed that miR-214-3p and miR-342-5p had the highest accuracy as individual biomarkers at predicting AF, but that a combined analysis of all four miRNAs slightly improved this accuracy.
“The same two miRNAs showed increased expression in a subset of patients with intermittent AF and another subset with chronic AF,” corresponding author Tetsuo Sasano says. “The increases were in comparison both with healthy controls of the same age and young healthy controls, suggesting these miRNAs may predict AF regardless of the age of the individual.”
Tokyo Medical and Dental University (TMDU)www.tmd.ac.jp/english/press-release/20180313/index.html

Orion Corporation (“Orion”) had announced last January that it was evaluating strategic alternatives of the Group’s Orion Diagnostica business division and had decided to investigate the possible sale of Orion Diagnostica as one alternative. Orion has now signed an agreement on the sale of all shares in Orion Diagnostica Oy (i.e. the Orion Diagnostica business division) to an investment fund managed by Axcel Management A/S, a leading Nordic private equity investment company (“Axcel”). The closing of the transaction is expected to take place during the second quarter of 2018. The closing is not conditional upon the parties obtaining approvals from competition law or other authorities or fulfilment of other preconditions.
The fixed purchase price is approximately EUR 163 million. In addition, Orion has a possibility to receive a variable component of EUR 60 million maximum. The payment of this variable component is based on return on investment for Axcel at the time of their exit. Orion estimates a capital gain of about EUR 128 million in other operating income for 2018. Due to the uncertainty relating to the variable component, the estimated capital gain does not include any part of the variable component.
“Orion Diagnostica has operated as an independent business and it has no material business synergies with Orion’s other operations. The sale of the division will allow us to further focus on growth and achieving our financial goals. Orion is currently working on numerous projects that target growth in our core area of the pharmaceuticals business. For example, we are actively evaluating late stage in-licensing opportunities. We also continue to invest in our own research and development activities, with new clinical trials, for example. The capital gain from the transaction will strengthen our equity position and maintain our ability to achieve our dividend distribution objective”, says Timo Lappalainen, President and CEO of Orion.
“Together with Orion Diagnostica’s management and employees, we intend to further develop the company into an even stronger operator in the global diagnostics market. On the back of an attractive customer proposition and a strong market position, we see great opportunity to grow Orion Diagnostica further both geographically and by expanding its product offering”, says Thomas Blomqvist, Partner at Axcel.
www.oriondiagnostica.com

Patients with gallbladder cancer often show few or no symptoms for long periods of time. As a result, the tumours are only detected at a late stage of the disease when treatment is often no longer possible. Working in collaboration with pathologists at the University of Magdeburg, Sonja M. Kessler, a research pharmacist in the group led by Professor Alexandra K. Kiemer at Saarland University, has identified a new pathway that may allow improved prognosis and treatment of the disease. Kessler has discovered a protein that is linked with tumour growth and that functions as a prognostic marker, thus providing an indication of how the cancer may progress.
The three proteins usually targeted by pharmacist Sonja M. Kessler in her research work are known to play an important role in embryos in the womb. These proteins help to ensure the rapid growth and development of the unborn child. After birth, however, these proteins typically play no further role. ‘All of these proteins are switched off after birth and they are no longer copied from the child’s genetic blueprint,’ explains licenced pharmacist Dr. Sonja M. Kessler, who is carrying out research at Saarland University in the group run by Professor Alexandra K. Kiemer for her Habilitation – the advanced research degree that entitles the holder to teach at professorial level within the German higher education system. However, it turns out that this family of proteins with the unremarkable names IMP1 to 3 can be switched on again. And if that happens, they can cause a lot of harm. Of the three proteins, IMP2 is particularly hostile: ‘Because IMP2 promotes cell division and proliferation, it also drives the growth of tumours,’ explains Kessler.
Research pharmacist Kessler has now succeeded in linking the protein group to gallbladder cancer. ‘We were able to identify the proteins in a large number of tissue samples from gallbladder patients. We were also able to show that the tumour grows faster when the cells contain larger amounts of the IMP2 protein. And in those cases patient prognosis is poorer,’ says Kessler.
This result from a basic research programme may in future help to improve gallbladder treatment. ‘Up until now there have been very few prognostic markers for this tumour,’ says Sonja Kessler. Prognostic markers are substances in blood or tissue samples that indicate that a malignant cancer is likely to have a poor outcome for the patient. Currently available treatment options can therefore be tailored more closely to the patient’s needs, which may help to improve clinical outcomes. IMP2 represents an important and potentially useful prognostic marker for gallbladder cancer. The results of Kessler’s research may also provide the basis for new effective drug treatments. Once the participating protein has been identified, research can be undertaken to influence, slow or even completely prevent the harmful processes that are set in motion by the protein.
University of Saarlandes
www.uni-saarland.de/nc/en/news/article/nr/18177.html

A study by the University of Tampere in Finland used protein profiling to find new prostate cancer mechanisms that are not shown by aberrations at the genomic level. Several new potential biomarkers of prostate cancer were also found.
Genes that affect prostate cancer evolution have been studied for a long time. However, changes in the protein levels are not well known.
The Center for Prostate Cancer Research and the Center for Proteomics and Personalized Medicine at the University of Tampere cooperated to profile the protein expression of prostate cancer by using mass spectrometry for the first time. The researchers compared protein expression to genomic and messenger RNAs in the same samples.
The result was that the changes in gene copy numbers and DNA methylation largely explain messenger RNA expression but not the changes on the protein level. The association between messenger RNA expression and protein levels was also weak. The study thus uncovered such mechanisms of prostate cancer that are not indicated by the alterations at the genomic level.
“In particular, changes in the citric acid cycle emerged in our analyses,” Adjunct Professor Leena Latonen says.
“The results enable exploring the significance of these changes," Latonen continues.
In addition to the disease mechanisms, protein profiling revealed several potential new biomarkers.
According to Professor Tapio Visakorpi, biomarkers able to recognize the aggressive forms of prostate cancer would be especially useful. That is one of the aspects on which the researchers will focus next.
“Discovering these protein biomarkers was enabled by the long-term interdisciplinary work of the research groups on the Kauppi campus of the University of Tampere,” says Professor Hannu Uusitalo, Director of the Center for Proteomics and Personalized Medicine.
University of Tamperewww.uta.fi/en/news/story/proteins-reveal-new-mechanisms-prostate-cancer

Two patients with mycosis fungoides (MF) can appear to have identical diseases upon first diagnosis but can have radically different outcomes. MF in an unusual cancer of the T lymphocyte that begins in the skin rather than in the lymph nodes, with the first sign often being a rash. Most patients with MF, the most common type of cutaneous T cell lymphoma (CTCL), have a very slow-growing disease and often have normal life expectancies. But a subset of patients will develop an aggressive, deadly form of the disease that can spread throughout the skin and beyond, becoming untreatable. If identified early, patients with this aggressive form of MF may be eligible for a stem cell transplant to cure the disease, but once MF progresses and becomes treatment resistant, it is nearly impossible to achieve the complete remission required for a successful stem cell transplant.
A tool to accurately determine which early-stage patients are at risk of dying from MF and which patients are likely to only require conventional therapy is desperately needed. Investigators from Brigham and Women’s Hospital have found that next-generation, high-throughput sequencing of a specific gene (T-cell receptor beta or TCRB) is a stronger predictor of which early-stage patients will develop aggressive, progressive MF than any other established factor.
“We are excited to bring precision medicine to the management of MF patients,” said senior author Thomas Kupper, MD, chair of the BWH Department of Dermatology. “While more work needs to be done, we think this approach has the potential to prospectively identify a subgroup of patients who are destined to develop aggressive, life-threatening disease, and treat them in a more aggressive fashion with the intent to better manage, and ideally cure, their cancer.”

Brigham and Women’s Hospitalwww.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=3009