Cancer rates in developing nations have climbed sharply in recent years, and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes, but screening approaches such as mammograms and colonoscopy, used in the developed world, are too costly to be implemented in settings with little medical infrastructure.
To address this gap, MIT engineers have developed a simple, cheap, paper test that could improve diagnosis rates and help people get treated earlier. The diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person has cancer. This approach has helped detect infectious diseases, and the new technology allows non-communicable diseases to be detected using the same strategy.
The technology, developed by MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, relies on nanoparticles that interact with tumour proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient’s urine.
‘When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis,’ says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. ‘For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.’
In 2012, Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumour proteins that would be hard to detect on their own. These proteins, known as matrix metalloproteinases (MMPs), help cancer cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.
The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumour sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.
In the original version of the technology, these peptides were detected using an instrument called a mass spectrometer, which analyses the molecular makeup of a sample. However, these instruments are not readily available in the developing world, so the researchers adapted the particles so they could be analysed on paper, using an approach known as a lateral flow assay — the same technology used in pregnancy tests.
To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.
In tests in mice, the researchers were able to accurately identify colon tumours, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients.
MIT
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Cancer cells have long been known to have higher rates of the energy-generating metabolic pathway known as glycolysis. This enhanced glycolysis, a phenomenon known as the Warburg effect, is thought to allow cancer cells to survive the oxygen-deficient conditions they experience in the centre of solid tumours. A study reveals how damaged cells normally switch off glycolysis as they shut down and shows that defects in this process may contribute to the early stages of tumour development.
Various stresses can cause cells to cease proliferating and enter an inactive state known as ‘senescence’ that prevents their transformation into tumour cells. In 2005, Hiroshi Kondoh and colleagues found that cells normally limit glycolysis as they enter senescence and that increasing the levels of the glycolytic enzyme PGAM can prevent cells from exiting the cell cycle. PGAM is increased in many tumours, stimulating glycolysis and other important pathways. But how cells regulate PGAM has been unclear.
Working at Kyoto University in Japan, Kondoh and colleagues followed up on their previous work and found that, in response to DNA damage or oncogene expression, PGAM was degraded, thereby inhibiting glycolysis as the cells entered senescence. The enzyme Mdm2 targeted PGAM for degradation in response to these senescence-inducing stresses.
‘Mdm2 can clearly, in some cases, act as a tumor suppressor by destabilizing PGAM,’ says Kondoh. Recent studies have emphasized the importance of PGAM as a therapeutic target for cancer management. Identifying the modulators of PGAM stability might open up new avenues for intervention.
EurekAlert
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The Icahn School of Medicine at Mount Sinai announced the launch of a more accurate carrier screening test for spinal muscular atrophy (SMA), one of the most common and severe autosomal recessive disorders. This new test will help prospective parents more effectively identify whether they carry the mutation that will affect their offspring. The test screens for genetic variation discovered by Mount Sinai researchers, which has been demonstrated to identify silent carriers of SMA in certain populations with higher accuracy and offers more accurate risk estimates than existing tests in all ethnic groups tested. Mount Sinai will be licensing the new test to other clinical laboratories to facilitate access to more accurate SMA carrier screening for as many people as possible.
SMA is an autosomal recessive disease that affects about 1 in 10,000 people and is one of the most deadly genetic diseases among infants and toddlers. It is transmitted by carrier parents who have no symptoms themselves; as many as 1 in 35 people may carry an SMN1 gene mutation, which is the gene that is defective in SMA. The disease kills nerve cells in the spinal cord, causing progressive degeneration among patients and diminishing capacity for walking, breathing, and swallowing. Severe forms of SMA are fatal, and there is currently no cure for the disease.
Scientists at the Mount Sinai Genetic Testing Laboratory recently used next-generation DNA sequencing to discover a new SMN1 genetic pattern that more accurately predicts the risk of having children with this disease. Current SMA carrier screening tests may result in false negative results due to their inability to detect silent carriers with two copies of the SMN1 gene on one chromosome and no copies on the other. The Mount Sinai Genetic Testing Laboratory’s patent-pending enhanced SMA test identifies a novel haplotype that successfully distinguishes those duplicated genes. This work significantly improves detection rates in the Ashkenazi Jewish population and improves risk estimates after a negative carrier screen for SMA in all ethnic groups.
‘People who choose to undergo carrier screening for spinal muscular atrophy do so to ensure that their future children will not suffer from this debilitating disease. It is important to provide patients with the most accurate risk estimates possible,’ said Lisa Edelmann, PhD, Director of the Mount Sinai Genetic Testing Laboratory. ‘Launching this enhanced test based on our recent scientific findings on SMN1 will provide more meaningful answers to these prospective parents, and it can also provide new information to people who have previously been screened with existing SMA carrier tests.’
The new test will be performed by the Genetic Testing Laboratory for all patients undergoing carrier screening for SMA. In addition, Mount Sinai will actively license the test to as many third-party clinical laboratories as possible.
Mount Sinai Health System
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An antibody found in the blood of people with multiple sclerosis (MS) may be present long before the onset of the disease and its symptoms, according to a study. ‘If our results can be replicated in larger populations, our findings may help to detect MS earlier in a subgroup of patients,’ said study author Viola Biberacher, MD, with Technical University in Munich, Germany. ‘Finding the disease before symptoms appear means we can better prepare to treat and possibly even prevent those symptoms. This finding also demonstrates that the antibody development to the KIR4.1 protein, a protein found in some people with MS, precedes the clinical onset of disease suggesting a role of the autoantibody in how the disease develops.’ For the study, 16 healthy blood donors who were later diagnosed with MS were compared to 16 healthy blood donors of the same age and sex who did not develop MS. Scientists looked for a specific antibody to KIR4.1. Samples were collected between two and nine months before the first symptoms of MS appeared. Next, researchers looked at antibody levels in the blood at additional time points up to six years before and then after disease onset in those who had the KIR4.1 antibody in their blood. All of the healthy controls tested negative for the KIR4.1 antibody. Of those who later developed MS, seven people tested positive for the antibodies, two showed borderline activity and seven were negative. In the study, KIR4.1 antibodies were found in the people with pre-clinical MS several years before the first clinical attack. Concentrations of the antibody varied at different time points during pre-MS in individual people. ‘The next step is to confirm these findings in larger groups and determine how many years before onset of disease the antibody response develops,’ said Biberacher
American Academy of Neurology
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An international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH) has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.
The current study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease. In the new study, researchers describe the genetic analysis of 150,000 patients showing that rare mutations in a gene called SLC30A8 reduce risk of type 2 diabetes by 65 percent. The results were seen in patients from multiple ethnic groups, suggesting that a drug that mimics the effect of these mutations might have broad utility around the globe. The protein encoded by SLC30A8 had previously been shown to play an important role in the insulin-secreting beta cells of the pancreas, and a common variant in that gene was known to slightly influence the risk of type 2 diabetes. However, it was previously unclear whether inhibiting or activating the protein would be the best strategy for reducing disease risk — and how large an effect could be expected.
‘This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions — knowing which targets to go after,’ said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital.
The use of human genetics to identify protective mutations holds great potential. Mutations in a gene called CCR5 were found to protect against infection with HIV, the virus that causes AIDS; drugs have been developed that block the CCR5 protein. A similar protective association for heart disease set off a race to discover new cholesterol-lowering drugs when mutations in the gene PCSK9 were found to lower cholesterol levels and heart disease risk. The new type 2 diabetes study suggests that CCR5 and PCSK9 are likely just the beginning but that it will take large numbers of samples and careful sleuthing to find additional genes with similar protective properties.
The study grew out of a research partnership that started in 2009 involving the Broad Institute, Massachusetts General Hospital, Pfizer Inc., and Lund University Diabetes Centre in Sweden, which set out to find mutations that reduce a person’s risk of type 2 diabetes. The research team selected people with severe risk factors for diabetes, such as advanced age and obesity, who never developed the disease and in fact had normal blood sugar levels. They focused on a set of genes previously identified as playing a role in type 2 diabetes and used next-generation sequencing to search for rare mutations.
The team identified a genetic mutation that appeared to abolish function of the SLC30A8 gene and that was enriched in non-diabetic individuals studied in Sweden and Finland. The protection was surprising, because studies in mice had suggested that mutations in SLC30A8 might have the opposite effect — increasing rather than decreasing risk of type 2 diabetes. However, because this particular genetic variation was exceedingly rare outside of Finland, it proved difficult to obtain additional evidence to corroborate the initial discovery by the Broad/MGH/Pfizer Inc./Lund team.
Then, in 2012, these unpublished results were shared with deCODE genetics, who uncovered a second mutation in an Icelandic population that also appeared to abolish function of the gene SLC30A8. That mutation independently reduced risk for type 2 diabetes and also lowered blood sugar in non-diabetics without any evident negative consequences.
‘This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk,’ said Kari Stefannson, CEO of deCODE genetics.
Finally, the team set out to ask if the effects of SLC30A8 protective mutations were limited to the two mutations found in populations in Finland and Iceland. As part of the NIH-funded T2D-GENES Project, chaired by Mike Boehnke at the University of Michigan, the Broad Institute had performed sequencing of 13,000 samples drawn from multiple ethnicities. The T2D-GENES Project joined the collaboration, found ten more mutations in the same gene, and again saw a protective effect. Combining all the results confirmed that inheriting one copy of a defective version of SLC30A8 led to a 65 percent reduction in risk of diabetes.
‘Through this partnership, we have been able to identify genetic mutations related to loss of gene function, which are protective against type 2 diabetes,’ said Tim Rolph, Vice President and Chief Scientific Officer of Cardiovascular, Metabolic & Endocrine Disease Research at Pfizer Inc. ‘Such genetic associations provide important new insights into the pathogenesis of diabetes, potentially leading to the discovery of drug targets, which may result in a novel medicine.’
Broad Institute
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In most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, Columbia researchers report.
The toxin is produced by star-shaped cells called astrocytes and kills nearby motor neurons. In ALS, the death of motor neurons causes a loss of control over muscles required for movement, breathing, and swallowing. Paralysis and death usually occur within 3 years of the appearance of first symptoms.
The report follows the researchers’ previous study, which found similar results in mice with a rare, genetic form of the disease, as well as in a separate study from another group that used astrocytes derived from patient neural progenitor cells. The current study shows that the toxins are also present in astrocytes taken directly from ALS patients.
‘I think this is probably the best evidence we can get that what we see in mouse models of the disease is also happening in human patients,’ said the study’s senior author, Serge Przedborski, MD, PhD, the Page and William Black Professor of Neurology (in Pathology and Cell Biology), Vice Chair for Research in the department of Neurology, and co-director of Columbia’s Motor Neuron Center.
The findings also are significant because they apply to the most common form of ALS, which affects about 90 percent of patients. Scientists do not know why ALS develops in these patients; the other 10 percent of patients carry one of 27 genes known to cause the disease.
‘Now that we know that the toxin is common to most patients, it gives us an impetus to track down this factor and learn how it kills the motor neurons,’ Dr. Przedborski said. ‘Its identification has the potential to reveal new ways to slow down or stop the destruction of the motor neurons.’
In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.
Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.
The researchers confirmed that the cause of the motor neurons’ death was a toxin released into the environment by immersing healthy motor neurons in the astrocytes’ culture media. The presence of the media, even without astrocytes, killed the motor neurons.
The researchers have not yet identified the toxin released by the astrocytes. But they did discover the nature of the neuronal death process triggered by the toxin. The toxin triggers a biochemical cascade in the motor neurons that essentially causes them to undergo a controlled cellular explosion.
Drs. Przedborski, Re, and Le Verche found that they could prevent astrocyte-triggered motor neuron death by inhibiting one of the key components of this molecular cascade.
These findings may lead to a way to prevent motor neuron death in patients and potentially prolong life. But the therapeutic potential of such inhibition is far from clear. ‘For example, we don’t know if this would leave patients with living but dysfunctional neurons,’ Dr. Przedborski said. The researchers are now testing the idea of inhibition in animal models of ALS.
The development of new therapies for ALS has been disappointing, with more than 30 clinical trials ending with no new treatments since the 1995 FDA approval of riluzole.
The lack of progress may be partly because animal models used to study ALS do not completely recreate the human disease. The new all-human cell model of ALS created for the current study may improve scientists’ ability to identify useful drug targets, particularly for the most common form of the disease.
‘Although there are many neuro-degenerative disorders, only for a handful do we have access to a simplified model that is relevant to the disease and can therefore potentially be used for high-throughput drug screening. So this model is quite special,’ Dr. Przedborski said. ‘Here we have a spontaneous disease phenotype triggered by the relevant tissue that causes human illness. That’s one important thing. The other important thing is that this model is derived entirely from human elements. This is probably the closest, most natural model of human ALS that we can get in a dish.’
Columbia University Medical Center
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Neuroblastoma is one of the most common and lethal types of childhood cancers. A researcher at the University of Texas Health Science Center at San Antonio unveils the important role of microRNAs in regulating neuroblastoma development, pointing to new therapeutic possibilities.
Neuroblastomas, which account for 15 percent of childhood cancer deaths, happen when some cells do not differentiate and grow as they should. A promising type of therapy called differentiation therapy targets these malignant cells so that they can resume the process of differentiating into mature cells.
Unlike conventional chemotherapies, this new approach to cancer therapy has fewer toxic side effects, and gives hope for a cancer treatment that is gentler on young bodies. But so far only a few differentiation agents have been successfully used to treat neuroblastoma, and more than half of the young patients treated with such agents still see their cancer return.
To find new treatments, researchers needed improved laboratory screening techniques, and now one has been developed by Liqin Du, Ph.D., an assistant professor in the Department of Cellular and Structural Biology, and her team at the Greehey Children’s Cancer Research Institute at the UT Health Science Center.
MicroRNAs are small RNA molecules involved in gene expression, and play an important role in cell development. This screening approach revealed several microRNA molecules that induce the process of cell differentiation, and those are key to developing new drugs.
‘Development of new agents for treating neuroblastoma has been greatly hampered by the lack of efficient high-throughput screening approaches,’ Dr. Du said. ‘In our study, we applied a novel high-content screening approach that we recently developed to investigate the role of microRNAs in neuroblastoma differentiation.
‘We identified a set of novel microRNAs that are potent inducers of neuroblastoma cell differentiation and found that mimics (synthetic fragments of nucleic acid used to raise microRNA levels in cells) of some of the identified microRNAs are much more potent in inducing neuroblastoma cell differentiation than the current differentiation treatments.
‘These mimics are promising new drugs for neuroblastoma differentiation therapy,’ Dr. Du said. ‘We look forward to investigating this further in the future.’
UT Health Science Center San Antonio
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Before doctors like Matthias Kretzler can begin using the results of molecular research to treat patients, they need science to find an effective way to match genes with the specific cells involved in disease. As Kretzler explains, finding that link would eventually let physicians create far more effective diagnostic tools and treatments.
‘Among many uses, it would allow us to develop cell-type targeted therapies,’ said Kretzler, a University of Michigan professor of internal medicine and computational medicine and bioinformatics. He recently collaborated with Princeton University professor Olga Troyanskaya on a way to match genes to cells. ‘If you identify a [disease] that is in the liver or in the kidney, you could target those areas and not affect other parts of the body,’ he said.
Although scientists have decoded the human genome — the list of all the genes in human cells — they still have great difficulty determining the specific genes that are activated to make a kidney cell as opposed to a liver or heart cell.
In theory, an easy way to link genes to cells would be to isolate a cell and test it. However, solid human tissue is so closely packed that even the finest surgical techniques cannot separate types of cells efficiently enough for analysis. A kidney biopsy, for example, produces a mix of several different types of cells that Kretzler dismisses as ‘kidney soup.’
Princeton University and University of Michigan researchers have developed a system that allows computers to ‘virtually dissect’ a kidney in a way that surgery cannot. The machine uses data from an array of gene-activity measurements in patients’ kidney biopsies to mathematically separate cells and identify genes that are turned on in a specific cell type. The researchers identified 136 genes involved in the creation of a critical kidney cell called a podocyte, tiny cells that serve as filters in the kidneys and are frequently involved in kidney disease.
‘We call it in-silico nano-dissection,’ said Troyanskaya, a professor of computer science and the Lewis-Sigler Institute for Integrative Genomics. Using a large database of such gene-activity measurements to track genetic lineage allows scientists to refine their analysis through thousands of measurements, something that would be impossible with individual cell cultures, she said.
The method has proven far faster and significantly more effective than current techniques. Researchers from Kretzler’s lab at Michigan and Troyanskaya’s at Princeton reported that they had identified 136 genes involved in the creation of a critical kidney cell called a podocyte. In decades of research, only 46 had been previously identified.
‘The potential for this is huge,’ said Behzad Najafian, a University of Washington assistant professor of pathology who specializes in renal pathology. ‘I believe this novel technique, which is a significant improvement in cell lineage-specific gene-expression analysis, will not only help us understand the pathophysiology of kidney diseases better through biopsy studies, but also provides a strong tool for discovery or validation of cell-specific urine or plasma biomarkers.’
Princeton University
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A team of researchers from UCLA’s Henry Samueli School of Engineering and Applied Science has developed a Google Glass application and a server platform that allow users of the wearable, glasses-like computer to perform instant, wireless diagnostic testing for a variety of diseases and health conditions.
With the new UCLA technology, Google Glass wearers can use the device’s hands-free camera to capture pictures of rapid diagnostic tests (RTDs), small strips on which blood or fluid samples are placed and which change colour to indicate the presence of HIV, malaria, prostate cancer or other conditions. Without relying on any additional devices, users can upload these images to a UCLA-designed server platform and receive accurate analyses — far more detailed than with the human eye — in as little as eight seconds.
The new technology could enhance the tracking of dangerous diseases and improve public health monitoring and rapid responses in disaster-relief areas or quarantine zones where conventional medical tools are not available or feasible, the researchers said.
‘This breakthrough technology takes advantage of gains in both immunochromatographic rapid diagnostic tests and wearable computers,’ said principal investigator Aydogan Ozcan, the Chancellor’s Professor of Electrical Engineering and Bioengineering at UCLA and associate director of UCLA’s California NanoSystems Institute. ‘This smart app allows for real-time tracking of health conditions and could be quite valuable in epidemiology, mobile health and telemedicine.’
In addition to designing the custom RDT–reader app for Google Glass, Ozcan’s team implemented server processes for fast and high-throughput evaluation of test results coming from multiple devices simultaneously. Finally, the researchers developed a web portal where users can view test results, maps charting the geographical spread of various diseases and conditions, and the cumulative data from all the tests they have submitted over time.
To submit images for test results, Google Glass users only need to take photos of RTD strips or other commonly available in-home tests, then upload the images wirelessly through the device to the UCLA-designed web portal. The technology permits quantified reading of the results to a few-parts-per-billion level of sensitivity — far greater than that of the naked eye — thus eliminating the potential for human error in interpreting results, which is a particular concern if the user is a health care worker who routinely deals with many different types of tests.
To gauge the accuracy and efficiency of the technology, the UCLA team used an in-home HIV test designed by OraSure Technologies and a prostate-specific antigen test made by JAJ International. The researchers took images of tests under normal, indoor, fluorescent-lit room conditions. They submitted more than 400 images of the two tests, and the RDT reader and server platform were able to read the images 99.6 percent of the time. In every case in which the technology successfully read the images, it returned accurate and quantified test results, according to the team.
The researchers also tested more than 300 blurry images or images of the testing device taken under various natural-usage scenarios and achieved a read rate of 96.6 percent.
The UCLA Henry Samueli School of Engineering and Applied Science
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Significance: Understanding more about how the different types of cells in breast tissue develop improves our knowledge of breast cancer. TAZ represents a potential new target for drug therapies to treat aggressive types of breast cancer.
Background: In cancer, normal cells can become unpredictable or aggressive and thus difficult to treat with anti-cancer drugs. This is especially true in breast cancer. By identifying the genes responsible for this change in cells from breast tissue, researchers hope to identify a way to stop or reverse it.
In breast tissue, there are two main types of cells: luminal cells and basal cells. Normally luminal cells are ‘programmed’ by a particular class of proteins (transcription factors), which prevent them from becoming basal cells, and vice-versa.
Previous work led by Charlotte Kuperwasser, principal investigator, determined that some common forms of breast cancer originate from luminal cells while some rarer forms of breast cancer originate from basal cells.
Findings: The research team identified a gene, TAZ, which controls whether breast cells behave more like basal cells or more like luminal cells, information that might be important in understanding and potentially treating certain difficult-to-treat forms of breast cancer. TAZ helps to regulate how different genes operate in different cell types.
How the Study Was Conducted: The research team identified TAZ by testing the function of more than 1,000 genes to determine which were involved in ‘reprogramming’ luminal and basal cells, therefore reversing lineage commitment.
To further identify the role of TAZ, the research team studied breast tissue at different stages of development using two groups of mice: a control group with the TAZ gene and an experimental group of knock-out mice with the TAZ gene deleted. (Cells in breast tissue are renewed/developed during puberty, pregnancy, and nursing.)
The team also looked at the levels of the TAZ gene in tumours from women with either luminal or basal tumours.
Results: The research team found that the experimental group had an imbalance of cell populations in breast tissue: too many luminal and too few basal. The control group had a normal ratio of luminal to basal cells. In breast tissue from women with cancer, they found high levels of TAZ in basal but not luminal tumours.
Discussion: First author Adam Skibinski, M.D./Ph.D. student at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University:
‘We’ve known for a long time that breast cells can lose their normal identity when they become cancerous, but we are now realising that normal cells can change their characteristics as well in response to transcription factors like TAZ. This might be a factor in the development of breast cancer.’
Tufts University
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A paper diagnostic for cancer
, /in E-News /by 3wmediaCancer rates in developing nations have climbed sharply in recent years, and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes, but screening approaches such as mammograms and colonoscopy, used in the developed world, are too costly to be implemented in settings with little medical infrastructure.
To address this gap, MIT engineers have developed a simple, cheap, paper test that could improve diagnosis rates and help people get treated earlier. The diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person has cancer. This approach has helped detect infectious diseases, and the new technology allows non-communicable diseases to be detected using the same strategy.
The technology, developed by MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, relies on nanoparticles that interact with tumour proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient’s urine.
‘When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis,’ says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. ‘For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.’
In 2012, Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumour proteins that would be hard to detect on their own. These proteins, known as matrix metalloproteinases (MMPs), help cancer cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.
The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumour sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.
In the original version of the technology, these peptides were detected using an instrument called a mass spectrometer, which analyses the molecular makeup of a sample. However, these instruments are not readily available in the developing world, so the researchers adapted the particles so they could be analysed on paper, using an approach known as a lateral flow assay — the same technology used in pregnancy tests.
To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.
In tests in mice, the researchers were able to accurately identify colon tumours, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients. MIT
Mdm2 suppresses tumours by pulling the plug on glycolysis
, /in E-News /by 3wmediaCancer cells have long been known to have higher rates of the energy-generating metabolic pathway known as glycolysis. This enhanced glycolysis, a phenomenon known as the Warburg effect, is thought to allow cancer cells to survive the oxygen-deficient conditions they experience in the centre of solid tumours. A study reveals how damaged cells normally switch off glycolysis as they shut down and shows that defects in this process may contribute to the early stages of tumour development.
Various stresses can cause cells to cease proliferating and enter an inactive state known as ‘senescence’ that prevents their transformation into tumour cells. In 2005, Hiroshi Kondoh and colleagues found that cells normally limit glycolysis as they enter senescence and that increasing the levels of the glycolytic enzyme PGAM can prevent cells from exiting the cell cycle. PGAM is increased in many tumours, stimulating glycolysis and other important pathways. But how cells regulate PGAM has been unclear.
Working at Kyoto University in Japan, Kondoh and colleagues followed up on their previous work and found that, in response to DNA damage or oncogene expression, PGAM was degraded, thereby inhibiting glycolysis as the cells entered senescence. The enzyme Mdm2 targeted PGAM for degradation in response to these senescence-inducing stresses.
‘Mdm2 can clearly, in some cases, act as a tumor suppressor by destabilizing PGAM,’ says Kondoh. Recent studies have emphasized the importance of PGAM as a therapeutic target for cancer management. Identifying the modulators of PGAM stability might open up new avenues for intervention. EurekAlert
Laboratory launches more accurate carrier screening test for spinal muscular atrophy
, /in E-News /by 3wmediaThe Icahn School of Medicine at Mount Sinai announced the launch of a more accurate carrier screening test for spinal muscular atrophy (SMA), one of the most common and severe autosomal recessive disorders. This new test will help prospective parents more effectively identify whether they carry the mutation that will affect their offspring. The test screens for genetic variation discovered by Mount Sinai researchers, which has been demonstrated to identify silent carriers of SMA in certain populations with higher accuracy and offers more accurate risk estimates than existing tests in all ethnic groups tested. Mount Sinai will be licensing the new test to other clinical laboratories to facilitate access to more accurate SMA carrier screening for as many people as possible.
SMA is an autosomal recessive disease that affects about 1 in 10,000 people and is one of the most deadly genetic diseases among infants and toddlers. It is transmitted by carrier parents who have no symptoms themselves; as many as 1 in 35 people may carry an SMN1 gene mutation, which is the gene that is defective in SMA. The disease kills nerve cells in the spinal cord, causing progressive degeneration among patients and diminishing capacity for walking, breathing, and swallowing. Severe forms of SMA are fatal, and there is currently no cure for the disease.
Scientists at the Mount Sinai Genetic Testing Laboratory recently used next-generation DNA sequencing to discover a new SMN1 genetic pattern that more accurately predicts the risk of having children with this disease. Current SMA carrier screening tests may result in false negative results due to their inability to detect silent carriers with two copies of the SMN1 gene on one chromosome and no copies on the other. The Mount Sinai Genetic Testing Laboratory’s patent-pending enhanced SMA test identifies a novel haplotype that successfully distinguishes those duplicated genes. This work significantly improves detection rates in the Ashkenazi Jewish population and improves risk estimates after a negative carrier screen for SMA in all ethnic groups.
‘People who choose to undergo carrier screening for spinal muscular atrophy do so to ensure that their future children will not suffer from this debilitating disease. It is important to provide patients with the most accurate risk estimates possible,’ said Lisa Edelmann, PhD, Director of the Mount Sinai Genetic Testing Laboratory. ‘Launching this enhanced test based on our recent scientific findings on SMN1 will provide more meaningful answers to these prospective parents, and it can also provide new information to people who have previously been screened with existing SMA carrier tests.’
The new test will be performed by the Genetic Testing Laboratory for all patients undergoing carrier screening for SMA. In addition, Mount Sinai will actively license the test to as many third-party clinical laboratories as possible. Mount Sinai Health System
Antibody may be detectable in blood years before MS symptoms appear
, /in E-News /by 3wmediaAn antibody found in the blood of people with multiple sclerosis (MS) may be present long before the onset of the disease and its symptoms, according to a study. ‘If our results can be replicated in larger populations, our findings may help to detect MS earlier in a subgroup of patients,’ said study author Viola Biberacher, MD, with Technical University in Munich, Germany. ‘Finding the disease before symptoms appear means we can better prepare to treat and possibly even prevent those symptoms. This finding also demonstrates that the antibody development to the KIR4.1 protein, a protein found in some people with MS, precedes the clinical onset of disease suggesting a role of the autoantibody in how the disease develops.’ For the study, 16 healthy blood donors who were later diagnosed with MS were compared to 16 healthy blood donors of the same age and sex who did not develop MS. Scientists looked for a specific antibody to KIR4.1. Samples were collected between two and nine months before the first symptoms of MS appeared. Next, researchers looked at antibody levels in the blood at additional time points up to six years before and then after disease onset in those who had the KIR4.1 antibody in their blood. All of the healthy controls tested negative for the KIR4.1 antibody. Of those who later developed MS, seven people tested positive for the antibodies, two showed borderline activity and seven were negative. In the study, KIR4.1 antibodies were found in the people with pre-clinical MS several years before the first clinical attack. Concentrations of the antibody varied at different time points during pre-MS in individual people. ‘The next step is to confirm these findings in larger groups and determine how many years before onset of disease the antibody response develops,’ said Biberacher American Academy of Neurology
Study pinpoints protective mutations for type 2 diabetes
, /in E-News /by 3wmediaAn international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH) has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.
The current study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease. In the new study, researchers describe the genetic analysis of 150,000 patients showing that rare mutations in a gene called SLC30A8 reduce risk of type 2 diabetes by 65 percent. The results were seen in patients from multiple ethnic groups, suggesting that a drug that mimics the effect of these mutations might have broad utility around the globe. The protein encoded by SLC30A8 had previously been shown to play an important role in the insulin-secreting beta cells of the pancreas, and a common variant in that gene was known to slightly influence the risk of type 2 diabetes. However, it was previously unclear whether inhibiting or activating the protein would be the best strategy for reducing disease risk — and how large an effect could be expected.
‘This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions — knowing which targets to go after,’ said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital.
The use of human genetics to identify protective mutations holds great potential. Mutations in a gene called CCR5 were found to protect against infection with HIV, the virus that causes AIDS; drugs have been developed that block the CCR5 protein. A similar protective association for heart disease set off a race to discover new cholesterol-lowering drugs when mutations in the gene PCSK9 were found to lower cholesterol levels and heart disease risk. The new type 2 diabetes study suggests that CCR5 and PCSK9 are likely just the beginning but that it will take large numbers of samples and careful sleuthing to find additional genes with similar protective properties.
The study grew out of a research partnership that started in 2009 involving the Broad Institute, Massachusetts General Hospital, Pfizer Inc., and Lund University Diabetes Centre in Sweden, which set out to find mutations that reduce a person’s risk of type 2 diabetes. The research team selected people with severe risk factors for diabetes, such as advanced age and obesity, who never developed the disease and in fact had normal blood sugar levels. They focused on a set of genes previously identified as playing a role in type 2 diabetes and used next-generation sequencing to search for rare mutations.
The team identified a genetic mutation that appeared to abolish function of the SLC30A8 gene and that was enriched in non-diabetic individuals studied in Sweden and Finland. The protection was surprising, because studies in mice had suggested that mutations in SLC30A8 might have the opposite effect — increasing rather than decreasing risk of type 2 diabetes. However, because this particular genetic variation was exceedingly rare outside of Finland, it proved difficult to obtain additional evidence to corroborate the initial discovery by the Broad/MGH/Pfizer Inc./Lund team.
Then, in 2012, these unpublished results were shared with deCODE genetics, who uncovered a second mutation in an Icelandic population that also appeared to abolish function of the gene SLC30A8. That mutation independently reduced risk for type 2 diabetes and also lowered blood sugar in non-diabetics without any evident negative consequences.
‘This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk,’ said Kari Stefannson, CEO of deCODE genetics.
Finally, the team set out to ask if the effects of SLC30A8 protective mutations were limited to the two mutations found in populations in Finland and Iceland. As part of the NIH-funded T2D-GENES Project, chaired by Mike Boehnke at the University of Michigan, the Broad Institute had performed sequencing of 13,000 samples drawn from multiple ethnicities. The T2D-GENES Project joined the collaboration, found ten more mutations in the same gene, and again saw a protective effect. Combining all the results confirmed that inheriting one copy of a defective version of SLC30A8 led to a 65 percent reduction in risk of diabetes.
‘Through this partnership, we have been able to identify genetic mutations related to loss of gene function, which are protective against type 2 diabetes,’ said Tim Rolph, Vice President and Chief Scientific Officer of Cardiovascular, Metabolic & Endocrine Disease Research at Pfizer Inc. ‘Such genetic associations provide important new insights into the pathogenesis of diabetes, potentially leading to the discovery of drug targets, which may result in a novel medicine.’ Broad Institute
Toxin from brain cells triggers neuron loss in human ALS model
, /in E-News /by 3wmediaIn most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, Columbia researchers report.
The toxin is produced by star-shaped cells called astrocytes and kills nearby motor neurons. In ALS, the death of motor neurons causes a loss of control over muscles required for movement, breathing, and swallowing. Paralysis and death usually occur within 3 years of the appearance of first symptoms.
The report follows the researchers’ previous study, which found similar results in mice with a rare, genetic form of the disease, as well as in a separate study from another group that used astrocytes derived from patient neural progenitor cells. The current study shows that the toxins are also present in astrocytes taken directly from ALS patients.
‘I think this is probably the best evidence we can get that what we see in mouse models of the disease is also happening in human patients,’ said the study’s senior author, Serge Przedborski, MD, PhD, the Page and William Black Professor of Neurology (in Pathology and Cell Biology), Vice Chair for Research in the department of Neurology, and co-director of Columbia’s Motor Neuron Center.
The findings also are significant because they apply to the most common form of ALS, which affects about 90 percent of patients. Scientists do not know why ALS develops in these patients; the other 10 percent of patients carry one of 27 genes known to cause the disease.
‘Now that we know that the toxin is common to most patients, it gives us an impetus to track down this factor and learn how it kills the motor neurons,’ Dr. Przedborski said. ‘Its identification has the potential to reveal new ways to slow down or stop the destruction of the motor neurons.’
In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.
Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.
The researchers confirmed that the cause of the motor neurons’ death was a toxin released into the environment by immersing healthy motor neurons in the astrocytes’ culture media. The presence of the media, even without astrocytes, killed the motor neurons.
The researchers have not yet identified the toxin released by the astrocytes. But they did discover the nature of the neuronal death process triggered by the toxin. The toxin triggers a biochemical cascade in the motor neurons that essentially causes them to undergo a controlled cellular explosion.
Drs. Przedborski, Re, and Le Verche found that they could prevent astrocyte-triggered motor neuron death by inhibiting one of the key components of this molecular cascade.
These findings may lead to a way to prevent motor neuron death in patients and potentially prolong life. But the therapeutic potential of such inhibition is far from clear. ‘For example, we don’t know if this would leave patients with living but dysfunctional neurons,’ Dr. Przedborski said. The researchers are now testing the idea of inhibition in animal models of ALS.
The development of new therapies for ALS has been disappointing, with more than 30 clinical trials ending with no new treatments since the 1995 FDA approval of riluzole.
The lack of progress may be partly because animal models used to study ALS do not completely recreate the human disease. The new all-human cell model of ALS created for the current study may improve scientists’ ability to identify useful drug targets, particularly for the most common form of the disease.
‘Although there are many neuro-degenerative disorders, only for a handful do we have access to a simplified model that is relevant to the disease and can therefore potentially be used for high-throughput drug screening. So this model is quite special,’ Dr. Przedborski said. ‘Here we have a spontaneous disease phenotype triggered by the relevant tissue that causes human illness. That’s one important thing. The other important thing is that this model is derived entirely from human elements. This is probably the closest, most natural model of human ALS that we can get in a dish.’ Columbia University Medical Center
Improved lab screening technique opens door for new pediatric neuroblastoma therapies
, /in E-News /by 3wmediaNeuroblastoma is one of the most common and lethal types of childhood cancers. A researcher at the University of Texas Health Science Center at San Antonio unveils the important role of microRNAs in regulating neuroblastoma development, pointing to new therapeutic possibilities.
Neuroblastomas, which account for 15 percent of childhood cancer deaths, happen when some cells do not differentiate and grow as they should. A promising type of therapy called differentiation therapy targets these malignant cells so that they can resume the process of differentiating into mature cells.
Unlike conventional chemotherapies, this new approach to cancer therapy has fewer toxic side effects, and gives hope for a cancer treatment that is gentler on young bodies. But so far only a few differentiation agents have been successfully used to treat neuroblastoma, and more than half of the young patients treated with such agents still see their cancer return.
To find new treatments, researchers needed improved laboratory screening techniques, and now one has been developed by Liqin Du, Ph.D., an assistant professor in the Department of Cellular and Structural Biology, and her team at the Greehey Children’s Cancer Research Institute at the UT Health Science Center.
MicroRNAs are small RNA molecules involved in gene expression, and play an important role in cell development. This screening approach revealed several microRNA molecules that induce the process of cell differentiation, and those are key to developing new drugs.
‘Development of new agents for treating neuroblastoma has been greatly hampered by the lack of efficient high-throughput screening approaches,’ Dr. Du said. ‘In our study, we applied a novel high-content screening approach that we recently developed to investigate the role of microRNAs in neuroblastoma differentiation.
‘We identified a set of novel microRNAs that are potent inducers of neuroblastoma cell differentiation and found that mimics (synthetic fragments of nucleic acid used to raise microRNA levels in cells) of some of the identified microRNAs are much more potent in inducing neuroblastoma cell differentiation than the current differentiation treatments.
‘These mimics are promising new drugs for neuroblastoma differentiation therapy,’ Dr. Du said. ‘We look forward to investigating this further in the future.’ UT Health Science Center San Antonio
Tracking genes on the path to genetic treatment
, /in E-News /by 3wmediaBefore doctors like Matthias Kretzler can begin using the results of molecular research to treat patients, they need science to find an effective way to match genes with the specific cells involved in disease. As Kretzler explains, finding that link would eventually let physicians create far more effective diagnostic tools and treatments.
‘Among many uses, it would allow us to develop cell-type targeted therapies,’ said Kretzler, a University of Michigan professor of internal medicine and computational medicine and bioinformatics. He recently collaborated with Princeton University professor Olga Troyanskaya on a way to match genes to cells. ‘If you identify a [disease] that is in the liver or in the kidney, you could target those areas and not affect other parts of the body,’ he said.
Although scientists have decoded the human genome — the list of all the genes in human cells — they still have great difficulty determining the specific genes that are activated to make a kidney cell as opposed to a liver or heart cell.
In theory, an easy way to link genes to cells would be to isolate a cell and test it. However, solid human tissue is so closely packed that even the finest surgical techniques cannot separate types of cells efficiently enough for analysis. A kidney biopsy, for example, produces a mix of several different types of cells that Kretzler dismisses as ‘kidney soup.’
Princeton University and University of Michigan researchers have developed a system that allows computers to ‘virtually dissect’ a kidney in a way that surgery cannot. The machine uses data from an array of gene-activity measurements in patients’ kidney biopsies to mathematically separate cells and identify genes that are turned on in a specific cell type. The researchers identified 136 genes involved in the creation of a critical kidney cell called a podocyte, tiny cells that serve as filters in the kidneys and are frequently involved in kidney disease.
‘We call it in-silico nano-dissection,’ said Troyanskaya, a professor of computer science and the Lewis-Sigler Institute for Integrative Genomics. Using a large database of such gene-activity measurements to track genetic lineage allows scientists to refine their analysis through thousands of measurements, something that would be impossible with individual cell cultures, she said.
The method has proven far faster and significantly more effective than current techniques. Researchers from Kretzler’s lab at Michigan and Troyanskaya’s at Princeton reported that they had identified 136 genes involved in the creation of a critical kidney cell called a podocyte. In decades of research, only 46 had been previously identified.
‘The potential for this is huge,’ said Behzad Najafian, a University of Washington assistant professor of pathology who specializes in renal pathology. ‘I believe this novel technique, which is a significant improvement in cell lineage-specific gene-expression analysis, will not only help us understand the pathophysiology of kidney diseases better through biopsy studies, but also provides a strong tool for discovery or validation of cell-specific urine or plasma biomarkers.’ Princeton University
Google Glass app for instant medical diagnostic test results
, /in E-News /by 3wmediaA team of researchers from UCLA’s Henry Samueli School of Engineering and Applied Science has developed a Google Glass application and a server platform that allow users of the wearable, glasses-like computer to perform instant, wireless diagnostic testing for a variety of diseases and health conditions.
With the new UCLA technology, Google Glass wearers can use the device’s hands-free camera to capture pictures of rapid diagnostic tests (RTDs), small strips on which blood or fluid samples are placed and which change colour to indicate the presence of HIV, malaria, prostate cancer or other conditions. Without relying on any additional devices, users can upload these images to a UCLA-designed server platform and receive accurate analyses — far more detailed than with the human eye — in as little as eight seconds.
The new technology could enhance the tracking of dangerous diseases and improve public health monitoring and rapid responses in disaster-relief areas or quarantine zones where conventional medical tools are not available or feasible, the researchers said.
‘This breakthrough technology takes advantage of gains in both immunochromatographic rapid diagnostic tests and wearable computers,’ said principal investigator Aydogan Ozcan, the Chancellor’s Professor of Electrical Engineering and Bioengineering at UCLA and associate director of UCLA’s California NanoSystems Institute. ‘This smart app allows for real-time tracking of health conditions and could be quite valuable in epidemiology, mobile health and telemedicine.’
In addition to designing the custom RDT–reader app for Google Glass, Ozcan’s team implemented server processes for fast and high-throughput evaluation of test results coming from multiple devices simultaneously. Finally, the researchers developed a web portal where users can view test results, maps charting the geographical spread of various diseases and conditions, and the cumulative data from all the tests they have submitted over time.
To submit images for test results, Google Glass users only need to take photos of RTD strips or other commonly available in-home tests, then upload the images wirelessly through the device to the UCLA-designed web portal. The technology permits quantified reading of the results to a few-parts-per-billion level of sensitivity — far greater than that of the naked eye — thus eliminating the potential for human error in interpreting results, which is a particular concern if the user is a health care worker who routinely deals with many different types of tests.
To gauge the accuracy and efficiency of the technology, the UCLA team used an in-home HIV test designed by OraSure Technologies and a prostate-specific antigen test made by JAJ International. The researchers took images of tests under normal, indoor, fluorescent-lit room conditions. They submitted more than 400 images of the two tests, and the RDT reader and server platform were able to read the images 99.6 percent of the time. In every case in which the technology successfully read the images, it returned accurate and quantified test results, according to the team.
The researchers also tested more than 300 blurry images or images of the testing device taken under various natural-usage scenarios and achieved a read rate of 96.6 percent. The UCLA Henry Samueli School of Engineering and Applied Science
Study identifies gene important to breast development and breast cancer
, /in E-News /by 3wmediaSignificance: Understanding more about how the different types of cells in breast tissue develop improves our knowledge of breast cancer. TAZ represents a potential new target for drug therapies to treat aggressive types of breast cancer.
Background: In cancer, normal cells can become unpredictable or aggressive and thus difficult to treat with anti-cancer drugs. This is especially true in breast cancer. By identifying the genes responsible for this change in cells from breast tissue, researchers hope to identify a way to stop or reverse it.
In breast tissue, there are two main types of cells: luminal cells and basal cells. Normally luminal cells are ‘programmed’ by a particular class of proteins (transcription factors), which prevent them from becoming basal cells, and vice-versa.
Previous work led by Charlotte Kuperwasser, principal investigator, determined that some common forms of breast cancer originate from luminal cells while some rarer forms of breast cancer originate from basal cells.
Findings: The research team identified a gene, TAZ, which controls whether breast cells behave more like basal cells or more like luminal cells, information that might be important in understanding and potentially treating certain difficult-to-treat forms of breast cancer. TAZ helps to regulate how different genes operate in different cell types.
How the Study Was Conducted: The research team identified TAZ by testing the function of more than 1,000 genes to determine which were involved in ‘reprogramming’ luminal and basal cells, therefore reversing lineage commitment.
To further identify the role of TAZ, the research team studied breast tissue at different stages of development using two groups of mice: a control group with the TAZ gene and an experimental group of knock-out mice with the TAZ gene deleted. (Cells in breast tissue are renewed/developed during puberty, pregnancy, and nursing.)
The team also looked at the levels of the TAZ gene in tumours from women with either luminal or basal tumours.
Results: The research team found that the experimental group had an imbalance of cell populations in breast tissue: too many luminal and too few basal. The control group had a normal ratio of luminal to basal cells. In breast tissue from women with cancer, they found high levels of TAZ in basal but not luminal tumours.
Discussion: First author Adam Skibinski, M.D./Ph.D. student at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University:
‘We’ve known for a long time that breast cells can lose their normal identity when they become cancerous, but we are now realising that normal cells can change their characteristics as well in response to transcription factors like TAZ. This might be a factor in the development of breast cancer.’ Tufts University