A new blood test allowing doctors to predict which ovarian cancer patients will respond to particular types of treatment is a step closer following a new study by Manchester scientists.
Researchers from The University of Manchester and The Christie NHS Foundation Trust – both part of Manchester Cancer Research Centre – say the test could be developed and used in hospitals within the next few years.

It would mean medics could see which patients could benefit from blood vessel-targeting drugs – such as bevacizumab – in addition to conventional therapy. Meanwhilehile others who are not going to benefit would be spared the time and side effects associated with having the drug.  The test would also help to reduce the cost to the NHS.

Ovarian cancer has seen little increase in survival rates over the last few decades and scientists are seeking new treatment strategies to improve the standard approach of surgery and chemotherapy.

A recent advance has been to target the development of new blood vessels within the tumour – preventing the cancer from receiving the nutrients it needs to grow.

Bevacizumab, one of the blood vessel-targeting drugs, has shown significant but modest improvements in patient survival so doctors are seeking ways to predict which patients are most likely to gain an advantage from this type of drug.

The research team looked at blood samples from patients enrolled in an international trial of bevacizumab. These patients received either standard chemotherapy treatment alone or chemotherapy plus the blood vessel-targeting drug.

Professor Gordon Jayson, Professor of Medical Oncology at The University of Manchester and Honorary Consultant at The Christie who jointly led the study, said: ‘We are keen to identify predictive biomarkers – measures that can indicate how well a patient will respond to treatment – so we can better target these drugs to patients most likely to benefit.
‘We investigated levels of a range of proteins in patients’ pre-treatment blood samples to see if any were associated with improved survival.’

The findings show that two particular proteins – Ang1 and Tie2 – could be used in combination to predict patient response. Patients with high levels of Ang1 and low levels of Tie2 were most likely to benefit from bevacizumab. Both these proteins are involved in controlling the formation of new blood vessels. Conversely, they found that patients with high levels of both proteins did not benefit from the additional drug.

Study co-author Professor Caroline Dive, from the Cancer Research UK Manchester Institute based at The University of Manchester, added: ‘We will now look to further explore the potential of using a blood test to personalise treatment for ovarian cancer patients. Moving towards a more individualised treatment plan specific for each patient and their particular tumour is key to improving outcomes for patients while sparing those unlikely to benefit from potential side effects of therapy.’ University of Manchester

People with blood type AB may be more likely to develop memory loss in later years than people with other blood types, according to a study published by Kristine Alexander, Ph.D., postdoctoral fellow in medicine, Mary Cushman, M.D., M.Sc., professor of medicine at the University of Vermont College of Medicine, and colleagues.

AB is the least common blood type, found in only about four percent of the U.S. population. The study found that people with AB blood were 82 percent more likely to develop the thinking and memory problems that can lead to dementia than people with other blood types. Previous studies have shown that people with type O blood have a lower risk of heart disease and stroke, factors that can increase the risk of memory loss and dementia.

The study was part of a larger study (the REasons for Geographic And Racial Differences in Stroke, or REGARDS Study) of more than 30,000 people followed for an average of 3.4 years. In those who had no memory or thinking problems at the beginning, the study identified 495 participants who developed thinking and memory problems, or cognitive impairment, during the study. They were compared to 587 people with no cognitive problems.

People with AB blood type made up 6 percent of the group who developed cognitive impairment, which is higher than the 4 percent found in the population.

“Our study looks at blood type and risk of cognitive impairment, but several studies have shown that factors such as high blood pressure, high cholesterol and diabetes increase the risk of cognitive impairment and dementia,” says Alexander. “Blood type is also related to other vascular conditions like stroke, so the findings highlight the connections between vascular issues and brain health. More research is needed to confirm these results.”

In the study, researchers also looked at blood levels of factor VIII, a protein that helps blood to clot. High levels of factor VIII were related to higher risk of cognitive impairment. People in this study with higher levels of factor VIII were 24 percent more likely to develop thinking and memory problems than people with lower levels of the protein. People with AB blood had a higher average level of factor VIII than people with other blood types.

“For stroke, we found that about half of the association of blood type AB with stroke was due to differences between people in levels of clotting Factor VIII, but our current study of cognitive impairment did show this finding,” says Cushman, who adds that the differences in the findings of the two studies suggests that other reasons – not yet understood – are likely playing a role in explaining the impact on of blood type AB on cognitive function. Further research is needed to determine those details. University of Vermont

Scientists could soon better predict a man’s risk of getting prostate cancer after a worldwide team of researchers carried out the largest-ever analysis of the cancer’s genetic biomarkers.
QUT Institute of Health and Biomedical Innovation’s Dr Jyotsna Batra and Distinguished Professor Judith Clements, who led the Australian researchers in the large consortia of research hubs around the world, said the teams analysed more than 10 million genetic markers in 80,000 men.
‘It’s the largest analysis of genetic biomarkers ever done. We found another 23 new prostate cancer risk loci (sites) on the genome in addition to the 76 identified previously,’ Dr Batra said.
‘We now have 100 genetic regions and no other cancer has had this many loci identified to be associated with it. What we are looking for is the combination effect of how these loci work together and how much they can explain the heritability of prostate cancer.
‘The indications are that these genetic variants explain 33 per cent of the familial risk of the disease.

‘These are low-risk gene variants but what we have learnt is you can’t rely on just one gene to predict risk. You have to look at the total of the 100.
‘The top one per cent of men with these variants have a 5.7-fold relative risk compared with the population average.’
Dr Batra said that, in addition to family history, incorporating information regarding carrier status of these 100 risk variants could be valuable in defining risk levels in targeted screening and prevention programs for prostate cancer.
She said the multi-ethnic analysis of 80,000 individuals with prostate cancer found some risk variants were more common in different ethnic populations.
‘The aggressive form is prevalent in Africa and we found some risk genes specific to African populations,’ she said.
‘Of the 23 new variants we found 15 were in men of European ancestry and seven in the multi-ethnic analyses.’
Dr Batra said the sufferers of the non-aggressive form of prostate cancer outnumbered those with the aggressive form in the sample of 80,000 men.
‘Only 10 per cent of prostate cancers were the aggressive form in the current analysis,’ she said.
‘So far, we haven’t identified the loci for the aggressive form of the disease – research is ongoing on this. The next sample set will have more than 100,000 people with prostate cancer,’ she said.
‘Being able to predict the aggressive form before it goes on to spread is a goal of the future research because even after the prostate is removed a few cells can go on to kill the person.’ Queensland University of Technology

Researchers have identified a genetic/molecular network that fuels a high-risk and aggressive form of Acute Myeloid Leukaemia (AML) and its precursor disease Myelodysplastic Syndrome (MDS) – providing a possible therapeutic strategy for an essentially untreatable form of the blood cancer.

The specific forms of AML and MDS in the current study involve deletions on the arm of a specific chromosome in blood cells (del(5q). In patients with less aggressive forms of del(5q) MDS, the percentage of bone marrow blasts in their blood (the earliest, most immature cells of the myeloid cell line) is less than 5 percent. This means treatment prognosis for those patients typically is good, according to the study’s lead investigator, Daniel Starczynowski PhD, a researcher in the division of Experimental Hematology and Cancer Biology, part of the CBDI at Cincinnati Children’s.

“Unfortunately, a large portion of del(5q) AML and MDS patients have increased number of bone marrow blasts and additional chromosomal mutations,” Starczynowski said. “These patients have very poor prognosis because the disease is very resistant to available treatments such as chemotherapy and radiation. Finding new therapies is important and this study identifies new therapeutic possibilities.”

The researchers conducted their study in human AML/MDS cells and mouse models of del(5q) AML/MDS. They found that reduced expression of a certain gene in blood cells (miR-146a) led to activation of a molecular signalling network involving several components of NF-kB, one of which involved a protein called p62 – a critical regulator of cell metabolism, cellular remodelling and certain cancers.

Deletion of the miR-146a gene led to overexpression of p62, which caused sustained activation of what researchers identified as an NF-kB signalling network. This fuelled the survival and aggressive growth of leukemic cells in cells and in mouse models.

Earlier attempts in previous studies to directly inhibit NF-kB (a key molecular facilitator to the leukemic process) have not proven successful, according to investigators on the current paper. So the authors performed follow-up laboratory tests to look for possible vulnerabilities to NF-kB and a potential workaround by targeting instead p62 within the NF-kB signalling network.
The researcher next tested inhibiting/knocking down p62 as an experimental treatment strategy in mouse models of leukaemia and in human cells.  The authors reported that targeting p62 prevented expansion of leukemic cells in mouse models and reduced the number of leukaemia cell colonies by 80 percent in human AML/MDS cells.

Starczynowski stressed that significant additional research is needed to further verify the findings and learn more about the molecular processes involved. He also cautioned that laboratory results in mouse models do not necessarily translate to humans, and it isn’t known at this time how the findings might be directly applicable to clinical treatment. Cincinnati Children’s Hospital Medical Center

The first assay to meet the new CLSI H59-A* standards for exclusion of pulmonary embolism

03/09/2014 – Stago has received approval from the US Food and Drug Administration (FDA) for the reagent STA^® _–Liatest^® D-Di, in the exclusion of pulmonary embolism (PE) in patients with low or moderate risk, presenting at an emergency unit.
FDA requirements for D-dimer assays for exclusion are now based on the new and more restrictive standards established and published by the Clinical Laboratory Standards Institute (CLSI, H59-A). Stago’s rapid, automated and highly sensitive D-Dimer is thus the first test to comply with these new requirements.

In order to comply with the new CLSI guidelines, Stago performed a 2-years international prospective study similar to clinical studies performed in the pharmaceutical field (9 sites, 5 countries, more than 1100 patients, including evaluation of clinical pretest probability, imaging and 3 months of follow-up): a first in the field of Haemostasis diagnostics.

As its coordinator Prof. Gilles Pernod (Grenoble University Hospital, France) pointed out: 
“As well as providing the results required to validate this test for the exclusion of PE, this study brought to light some significant evolutions in clinical practice and shifts in prevalence. In fact, these findings will be presented in some interesting upcoming publications”.

This study also confirmed the excellent diagnostic performance of the STA^® -Liatest^® D-Di assay, with a very high negative predictive value (NPV) for the exclusion of PE, far exceeding FDA requirements (>99.7% versus 97%), and excellent sensitivity (>97% versus 95%).

The second part of this international clinical study, concerning deep vein thrombosis (DVT), is underway and due to be completed in the next few months. Let us hope that it provides the scientific community with as much relevant data as this first essential phase.

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