Thermo Fisher Scientific has established new collaborations of the Thermo Fisher Precision Medicine Science Center (PMSC) with AstraZeneca and the University of Nebraska Medical Center as part of its ongoing development of innovative solutions for unmet needs in clinical biomarker discovery. The new alliances strengthen the PMSC’s mission of creating standardized workflows with pharma and academic partners to streamline the transition from biomarker research to clinical implementation, creating new opportunities for precision medicine.
Ongoing and planned studies with both AstraZeneca and the University of Nebraska Medical Center will utilize standardized plasma protein profiling workflows, including Thermo Fisher’s newly developed ultra-high throughput plasma protein profiling (uHTPPP) workflow, for biomarker discovery, for a range of conditions. The standardized workflows consist of automated sample preparation for untargeted and targeted methods in combination with the Thermo Scientific Orbitrap Exploris 480 and Thermo Scientific Orbitrap Exploris 240 mass spectrometers.
“Precision medicine is becoming a greater area of interest across a range of different diseases and has, therefore, faced challenges effectively scaling to meet clinical needs,” said Emily Chen, senior director, PMSC. “The goal of the Precision Medicine Science Center is to construct end-to-end workflow solutions that generate impactful data from discovery studies with large human cohorts and to harness the power of molecular profiling to improve the outcomes of patient care. Our ongoing work with AstraZeneca and the University of Nebraska Medical Center are paramount to realizing the potential of these technologies.”
Ventzi Hristova, senior scientist, dynamic omics, antibody discovery and protein engineering, R&D at AstraZeneca, said: “Powered by technological innovation, omics is proving to be one of the richest sources of data in all of science. Clinical proteomics is an emerging field aimed at improving patient care through the development of sensitive, high-throughput methods for in-depth proteomic characterization of clinical samples. This collaboration aims to evaluate and establish a model for clinical proteomics, using advanced sample processing and downstream analytical applications, that has the potential to help us identify new drug targets and biomarkers.”

Continuing a series of groundbreaking discoveries begun in 2010 about the genetic causes of the third most common form of inherited muscular dystrophy, an international team of researchers led by a scientist at Fred Hutchinson Cancer Research Center has identified the genes and proteins that damage muscle cells, as well as the mechanisms that can cause the disease.
The discovery could lead to a biomarker-based test for diagnosing facioscapulohumeral muscular dystrophy (FSHD), and the findings have implications for developing future treatments as well as for cancer immunotherapies in general.
The work establishes a viable roadmap for how the expression of the DUX4 gene can cause FSHD. Whether this is the sole cause of FSHD is not known; however, the latest findings ‘are about as strong of evidence as you can get’ of the genetic link, said corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center’s Human Biology Division.
Tapscott and colleagues sought answers to the questions about what the DUX4 protein does both normally in the body and in the FSHD disease process. In the latest study, they identified that the DUX4 protein regulates many genes that are normally expressed in the male germ line but are abnormally expressed in FSHD muscle. Germ line cells are inherited from parents and passed down to their offspring.
‘This study is a significant step forward by solidifying that the DUX4 transcription factor causes this disease, while offering a number of viable mechanisms for why the muscle is damaged,’ Tapscott said. Transcription factors are tools that cells use to control gene expression. Genes that are ‘turned on’ in the body are ‘transcribed,’ or translated, into proteins.
Now that scientists know that targets for DUX4 are expressed in skeletal muscle, an antibody- or RNA-based test could be developed to diagnose FSHD by examining muscle tissue from a biopsy, Tapscott said. Such biomarker-based tests also could be used to determine how well new treatments are working to suppress FSHD.
The study also discovered that DUX4 regulates cancer/testis antigens. Cancer/testis antigens are encoded by genes that are normally expressed only in the human germ line, but are also abnormally expressed in various tumour types, including melanoma and carcinomas of the bladder, lung and liver.
‘This knowledge now gives us a way to manipulate the expression of cancer/ testis antigens, potentially opening the opportunity to use these antigens in a cancer vaccine,’ Tapscott said. Fred Hutchinson Cancer Research Center

Today, heterosexuals in Europe are at particular risk of carrying HIV for so long that they remain undiagnosed until their immune system starts to fail and they become ill.
An international study under the leadership of the HIV in Europe initiative has now revealed that a number of diseases, including herpes zoster and certain forms of cancer, should be on the list of indicators for having HIV – and thus serve to prompt health care professionals to suggest an HIV-test to their patients.
The new results and guidelines are to be debated at a major international HIV conference in Copenhagen on 19th-20th March.
‘At the HIV in Europe conference we will be discussing how to disseminate knowledge of the new HIV indicator diseases to non-HIV doctors and health care professionals across Europe,’ says Jens Lundgren, Co-chair of the HIV in Europe initiative.
He’s also a Professor of Viral Diseases at Rigshospitalet and the Faculty of Health and Medical Sciences at the University of Copenhagen, where he heads the Copenhagen HIV Programme, one of the leading HIV/AIDS centres in the world.
Half of all people living with HIV are diagnosed very late in the course of their chronic HIV infection. People infected through heterosexual transmission now comprise 42 per cent of these late presenters, as a study of 90,000 Europeans tested HIV positive since 2.000 shows.
UNAIDS has estimated that 2,5 million Europeans carry an HIV infection, and as many as 900 000 of these, are still unaware of this. Inside EU the numbers are 800.000 infected with 250.000 undiagnosed.
Ton Coenen, co-chair of the HIV in Europe initiative, Director of Aids Funds and Soa AIDS Nederland suggests that since the HIV/AIDS issue is no longer high on the agenda in many European countries, and since people have to actively choose to be HIV-tested, many perhaps no longer consider going for a test if they have had unsafe sex.
However, the sooner HIV-infected individuals receive a diagnosis and start therapy, the greater are their chances of survival and their quality of life. And new research also shows therapy lowers the risk of passing the infection on to someone else.
‘The currently situation shows that we need more effective testing strategies and guidelines,’ Ton Coenen continues. ‘More than 300 doctors, health care professionals, NGOs and health politicians from 40 European countries will be discussing this need at the conference on 19th and 20th of March, so we have the ideal forum for it.’
‘We already have a list of Aids defining diseases, the vast majority of which indicate a weak immune system. This is a symptom of HIV and should lead to an immediate HIV test,’ Professor Lundgren explains. ‘We nned to find people living with HIV sooner than is currently the case, but to do so requires that doctors and other health care professionals offer tests to people presenting with diseases indicative of a hidden and undiagnosed HIV infection earlier in the course of the disease.’
The HIV in Europe initiative took up this challenge in 2009 and started the HIDES study (HIV Indicator Diseases Across Europe), which investigated eight new diseases and how often they proved to be signs of an undiagnosed HIV infection among the 3588 patients in the study.
‘We could see that if an adult had a sexually transmitted infection, malignant lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B or C, ongoing mononucleosis-like illness, inexplicable, persistent decline in the number of circulating white blood cells, or seborrheic dermatitis/exanthema, the risk of HIV infection was so high that it would be cost-effectiveness for society to routinely offer them a test,’ Professor Lundgren says. He also emphasises that the new indicator diseases do not necessarily mean that the patient has HIV.
‘But the incidence of HIV is greater for these eight indicator diseases and they should encourage health care professionals to offer the patient an HIV test. Draft guidelines on how to ensure this throughout Europe are one of the topics we need to debate and decide on, before they can be implemented.’ University of Copenhagen

A malignancy-risk gene signature developed for breast cancer has been found to have predictive and prognostic value for patients with early stage non-small cell lung cancer. The advancement was made by researchers at Moffitt Cancer Center in Tampa.
According to corresponding author Dung-Tsa Chen, Ph.D., associate member with the Moffitt Biostatistics program, non-small cell lung cancer (NSCLC) accounts for 80-90 percent of all lung cancers. Patients with NSCLC have a 30-50 percent relapse rate after surgery and a 40-70 percent five-year survival rate. Although adjuvant chemotherapy (ACT) has increased survival rates and has become standard treatment for NSCLC, a proportion of patients do not derive any benefit from it.
‘Better prognostic tools have been needed to identify both patients with a high probability of relapse and those who would benefit from adjuvant chemotherapy,’ said Chen.
He added that the Moffitt researchers are confident that their newly tested malignancy-risk gene signature for NSCLC will provide that tool because their malignancy-risk gene signature is a proliferative gene signature, one associated with both cancer risk and progression.
According to the researchers, their findings suggest a ‘transferability’ of the malignancy-risk gene signature between breast cancer and NSCLC, a ‘unique feature not seen in other gene signatures derived for various tumor types.’
‘To the best of our knowledge, our study is the first to show a high consistency of the gene signature on both breast cancer and NSCLC,’ said Chen. ‘The gene signature demonstrated a statistically significant association with overall survival and other clinical predictors in NSCLC.’
Originally, the malignancy-risk signature gene was designed to distinguish between normal breast tissues and breast cancer tissues by identifying abnormal molecular structure. The Moffitt research team further applied the signature to tissue samples from 442 NSCLC patients in the Director’s Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.
‘Additionally, the malignancy-risk gene signature has demonstrated the potential to identify early-stage NSCLC patients who would be likely to benefit from adjuvant chemotherapy,’ explained Chen. ‘This malignancy-risk gene signature may provide an additional tool to help identify a subset of patients at high-risk for low overall survival and who may benefit from ACT.’
Study results revealed a predictive feature of the malignancy-risk gene signature with an ability to predict overall survival in NSCLC patients. Further, the malignancy-risk gene signature was able to consistently distinguish between low and high malignancy risk groups and correlate the groups by good to poor overall survival rates. Moffitt Cancer Center

‘The overactive bladder syndrome has become an accepted way to simplify a complex array of symptoms and leads people to believe that an overactive bladder is an independent disease in itself. However, the truth is not as simple as this, as there are usually several factors at work explaining the symptoms. This is also one of the reasons why so called overactive bladder medications often do not bring the hoped result,’ says Kari Tikkinen, MD, PhD, from the HUCS Department of Urology.
The article on overactive bladder syndrome, which was co-written by Tikkinen, who currently holds a senior researcher post at the McMaster University in Canada, and Anssi Auvinen, Professor of Epidemiology from the University of Tampere, was recently published. For the article, the researchers systematically reviewed the studies on overactive bladder and the channels through which these studies have been funded.
The authors argue that the symptoms of an ‘overactive bladder’ ought to be studied individually and not as an ambiguous constellation of symptoms. This way the underlying causes of the symptoms can be better understood and more effective treatments can be developed.
The expression ‘overactive bladder’ was coined at an industry-sponsored symposium held in 1997. The following year, the FDA approved the first drug for the treatment of ‘symptoms of overactive bladder’, after which the pharmaceutical industry launched high-profile, worldwide promotional campaigns for drugs aimed at treatment of the syndrome.
According to the current definition, overactive bladder (OAB) syndrome is defined as the presence of urinary urgency with or without urgency incontinence, usually with increased daytime frequency and nocturia in the absence of infection or other obvious pathology.
‘The definition is vague and ambiguous because it includes unspecific terms, such as ‘usually’ and ‘with or without’, and the unclear expression ‘other obvious pathology’,’ Tikkinen says and continues, ‘For the pharmaceutical industry this definition is probably quite useful, as it is partly the reason why one medicine can be prescribed to a large number of patients.’
Research into overactive bladder has increased significantly over the past ten years and the pharmaceutical industry has invested heavily in it. ‘It has previously been shown that research funded by commercial actors often ends up unpublished if the results don’t serve the interests of the company,’ Tikkinen points out.
Tikkinen and Auvinen also bring to the fore that in many studies on prevalence of overactive bladder, very mild symptoms have been classified as abnormal.
‘More independent, non-commercially funded research on the subject is needed. There are, in the end, a huge number of people who suffer from urinary urgency and increased urinary frequency, and current treatments are not bringing sufficient relief,’ Tikkinen says. EurekAlert