R-Biopharm Group recently announced a collaborative agreement with SSI, focusing on discovery and development of novel diagnostic approaches for the detection of tuberculosis infection. The development of new diagnostic assays in the area of infectious diseases is a priority for R-Biopharm, a company with 30 years of experience in providing testing solutions for Clinical Diagnostics and Food & Feed analysis. R-Biopharm Group operates in various countries including subsidiaries in the UK, USA, Italy, France, Latin America, Brazil, Spain, Belgium, Australia, India and China as well as by a worldwide extensive network of more than 120 distributors. “This collaborative agreement creates an opportunity to work with the world-leading scientists and inventors of novel biomarkers and vaccines in the area of tuberculosis research. Our Infectious Diseases Team is inspired to join efforts for the development of novel diagnostics for the tuberculosis patients throughout the world. At R-Biopharm we are concerned about rising numbers of tuberculosis cases and escalation of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). In cooperation with Statens Serum Institute we will have the potential to transform the current underserved market of tuberculosis diagnostics and provide alternative solutions for the detection of TB infection,” said Dr. Ralf Dreher, CEO and Founder of R-Biopharm Group. SSI is one of Denmark’s largest research institutions in the health sector with over a century of experience in research, development and manufacturing of biologics. Led by Professor Peter Andersen, the research and development team at SSI are at the forefront in the development of novel vaccines and diagnostic agents for major diseases affecting global health. The program has brought several novel vaccine candidates in clinical trial within TB and Chlamydia as well as provided the ground work for the current industry standard in diagnostic tests for tuberculosis infection (IGRAs). “We are excited for our collaboration with R-Biopharm, a leading industry partner in the field of infectious disease diagnostics. As a government research organization under the ministry of health, industrial involvement is pivotal to get our projects from the lab out to the benefit of patients. The strong research base at R-Biopharm is a great match for the SSI team and has been a fruitful synergy,” said Prof. Peter Andersen, Executive Vice President, Center for Vaccine Research at Statens Serum Institute. Under the agreement, R-Biopharm and SSI will collaborate on research and development and responsibility for the commercialization of potential products.
www.r-biopharm.com
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Siemens Healthineers is developing “The Enterprise Project” with the Hermes Pardini Group of Minas Gerais, Brazil. The Enterprise Project is the largest and most complex clinical analysis laboratory known to date and is expected to be capable of handling 110 million sample tubes per year upon completion. Siemens Healthineers, in collaboration with Inpeco, has designed and will deliver this fully automated multidisciplinary solution on an unprecedented scale, which will include at least 100 analysers—including more than 50 Atellica Solution clinical chemistry and immunoassay analysers from Siemens Healthineers, the largest IVD supplier in this project. The highly sophisticated solution will provide automation of clinical and operational workflow, from sample reception through testing to disposal. Sited in Vespasiano, Grande Belo Horizonte in Minas Gerais, the lab will occupy 3,500 square meters of floor space, will conduct operations 24 hours a day, and is expected to be fully operational during 2019. “The automation track will be more than 330 meters long upon completion and will be used to automatically transport and distribute sample tubes to specific analysers that can run the specific type of test requested by clinicians,” said Guilherme Collares, Chef Operations Officer of the Hermes Pardini Group. “Unlike conventional laboratory set-ups, where sample tubes have to be moved manually between different analysers, our enterprise lab is designed to employ a ‘one-touch, one workflow’ concept to eliminate the need for manual interventions, ensure sample traceability, and reduce the turnaround time to results. The Enterprise Project also will rely on Atellica Process Manager, an IT solution that delivers a 3D view of the laboratory configuration, to enable operators to manage alerts, control instruments and reagent monitoring remotely, and see test progression in real time. Siemens Healthineers will implement the first Laboratory Control Room, which will centralize management and provide holistic visibility of operations in the central Vespasiano laboratory, and other Hermes Pardini satellite lab units in São Paulo, Rio de Janeiro, Goiania, and Belo Horizonte.
https://tinyurl.com/y9h4mtgm
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A new blood test for pregnant women detects with 75-80 percent accuracy whether their pregnancies will end in premature birth. The technique can also be used to estimate a foetus’s gestational age — or the mother’s due date — as reliably as and less expensively than ultrasound. Developed by a team of scientists led by researchers at Stanford University, the tests could help reduce problems related to premature birth, which affects 15 million infants worldwide each year. Until now, doctors have lacked a reliable way to predict whether pregnancies will end prematurely, and have struggled to accurately predict delivery dates for all types of pregnancies, especially in low-resource settings. Stephen Quake, PhD, professor of bioengineering and of applied physics at Stanford, shares senior authorship with Mads Melbye, MD, visiting professor of medicine. The lead authors are former Stanford postdoctoral scholar Thuy Ngo, PhD, and Stanford graduate student Mira Moufarrej. The tests measure the activity of maternal, placental and foetal genes by assessing maternal blood levels of cell-free RNA, tiny bits of the messenger molecule that carry the body’s genetic instructions to its protein-making factories. The team used blood samples collected during pregnancy to identify which genes gave reliable signals about gestational age and prematurity risk. “We found that a handful of genes are very highly predictive of which women are at risk for preterm delivery,” said Melbye, who is also president and CEO of the Statens Serum Institute in Copenhagen. “I’ve spent a lot of time over the years working to understand preterm delivery. This is the first real, significant scientific progress on this problem in a long time.” The gestational-age test was developed by studying a cohort of 31 Danish women who gave blood weekly throughout their pregnancies. The women all had full-term pregnancies. The scientists used blood samples from 21 of them to build a statistical model, which identified nine cell-free RNAs produced by the placenta that predict gestational age, and validated the model using samples from the remaining 10 women. The estimates of gestational age given by the model were accurate about 45 percent of the time, which is comparable to 48 percent accuracy for first-trimester ultrasound estimates. This is the first real, significant scientific progress on this problem in a long time. Measuring cell-free RNA in mothers’ blood also could provide a wealth of new information about foetal growth, Ngo said. “This gives a super-high resolution view of pregnancy and human development that no one’s ever seen before,” she said. “It tells us a lot about human development in normal pregnancy.” To figure out how to predict preterm birth, the researchers used blood samples from 38 American women who were at risk for premature delivery because they had already had early contractions or had given birth to a preterm baby before. These women each gave one blood sample during the second or third trimester of their pregnancies. Of this group, 13 delivered prematurely, and the remaining 25 delivered at term. The scientists found that levels of cell-free RNA from seven genes from the mother and the placenta could predict which pregnancies would end early. “It’s mostly maternal genes,” Moufarrej said, noting that the genes that predict prematurity are different than those that give information about gestational age. “We think it’s mom sending a signal that she’s ready to pull the ripcord.” The scientists need to validate the new tests in larger cohorts of pregnant women before they can be made available for widespread use. The biological mechanism behind preterm birth is still a mystery, but the scientists plan to investigate the roles of the genes that signal prematurity to better understand why it happens. They also hope to identify targets for drugs that could delay premature birth. Other Stanford authors of the paper are graduate student Keli Liu; postdoctoral scholar Joan Camunas-Soler, PhD; research affiliates Wenying Pan, PhD, Jennifer Okamoto and Norma Neff, PhD; senior research scientist Ronald Wong; Robert Tibshirani, PhD, professor of biomedical data science and of statistics; Gary Shaw, DrPH, professor of pediatrics; and David Stevenson, MD, professor of pediatrics. This gives a super-high resolution view of pregnancy and human development Scientists from the Statens Serum Institute in Copenhagen, the University of Pennsylvania School of Medicine and the University of Alabama-Birmingham also contributed to the study. Quake, Tibshirani, Shaw and Stevenson are members of Stanford Bio-X; Tibshirani, Shaw and Stevenson are members of the Stanford Child Health Research Institute; Quake and Tibshirani are members of the Stanford Cancer Institute; Stevenson is an affiliate of the Stanford Woods Institute for the Environment; and Quake is a member of the Stanford Cardiovascular Institute, Stanford ChHEM-H and the Stanford Neurosciences Institute. The research was funded by the Bill and Melinda Gates Foundation, the March of Dimes Prematurity Research Center at Stanford University, the March of Dimes Prematurity Initiative Grant at the University of Pennsylvania and the Chan Zuckerberg Biohub, of which Quake is co-president. The Chan Zuckerberg Biohub has submitted a patent application for the new technology. Stanford’s departments of Bioengineering, Applied Physics and Pediatrics also supported the work. The Department of Bioengineering is jointly operated by the schools of Medicine and of Engineering.
Stanford Medicine med.stanford.edu/news/all-news/2018/06/blood-test-for-pregnant-women-can-predict-premature-birth.html
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Hip replacements relieve pain and restore mobility for hundreds of thousands of patients in the United States each year, but of the more than 400,000 hip replacements performed in the U.S. annually, about 10 percent will fail within 10 to 15 years. One main cause of this failure — which results in a need for a second hip replacement surgery (known as a revision surgery) — is the destruction of bone tissue around the replacement joint, a condition called osteolysis, which may cause the joint to loosen. Now a research team at Rush University Medical Center has identified a pair of biomarkers that indicate which patients are likely to develop osteolysis. The discovery could lead to tests that would enable surgeons to identify those patients in advance and adjust post-operative monitoring routines for them. It even might lead to treatments to prevent osteolysis in these patients. “We are hopeful that early biomarkers for implant loosening will alert surgeons to be especially vigilant in their follow-up of at-risk patients and may eventually lead to treatments delaying or avoiding the need for revision surgery,” said the paper’s senior author D. Rick Sumner, PhD, chairperson of the Department of Cell & Molecular Medicine in Rush Medical College and the Mary Lou Bell McGrew Presidential Professor for Medical Research. With the U.S. population aging, many individuals remaining very active late in life and others becoming heavier, hip replacements are projected to increase by 174 percent by 2030, with a projected 137 percent increase in the number of hip revision surgeries to fix or replace the failed implant over the same time period. “We need to find effective strategies to handle this demand. These joints need to last, if possible, for the rest of a patient’s life,” said Joshua Jacobs, MD, a co-investigator on the study. Jacobs is Rush University’s vice provost for research and the William A. Hark, MD/Susanne G. Swift Professor and chairperson of the Rush Department of Orthopedic Surgery. For their study, Sumner and his colleagues took what he calls “a candidate protein approach.” They drew on a previous review of medical literature they had conducted, which identified 40 possible biomarkers of future osteolysis development. They divided the markers into four groups based on their likelihood to predict osteolysis and focused on the two groups that were most likely. The researchers winnowed the field of candidate proteins by eliminating markers found in blood rather than urine and those for which tests weren’t readily available.
Two combined biomarkers provided strongest indication of risk Ultimately they tested for the presence of seven biomarkers and compared findings to the medical history of the patients – 16 of whom eventually had developed osteolysis. A biostatisican on the team then conducted an analysis to determine which combinations of the biomarkers correlated most with the osteolysis development. “We looked at each marker independently, but none of them worked that well by themselves. Then he looked at panels of markers,” Sumner explained. “When we did that, we found we got a much better discrimination between patients that developed osteolysis and those that did not.” The analysis found that a higher than normal levels of the connective tissue protein alpha CTX (a marker for bone resorption) and the immune response protein interleukin 6 (a marker of inflammation) were highly accurate in identifying patients at risk for osteolysis. The combination was detectable in patients up to six years before they were diagnosed with osteolysis.
Rush University www.rush.edu/news/press-releases/early-indicators-bone-loss-after-hip-replacement-discovered
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Greiner Bio-One had a successful business year in 2017, further reinforcing its market position thanks to strong growth, new sites and innovative product solutions. The takeover of its long-standing, exclusive distribution partners VACUETTE España and VACUETTE Portugal in March 2017 has enabled greater proximity to customers and targeted market cultivation. As a result of that takeover, Greiner Bio-One now has its own subsidiaries on two further key markets in Europe. In addition, the headquarters in Kremsmünster were expanded and an investment was made in a warehouse facility at the site in Hungary.
In July 2017, Greiner Bio-One acquired 90% of shares in Vigmed Holding AB, a listed technology and trade company based in Helsingborg, Sweden. That has enabled I.V. catheters with a safety mechanism to be added to the Preanalytics safety products range. Another innovation on the market is the MiniCollect Complete tube – a version in which the MiniCollect standard tube is irreversibly assembled in a carrier tube. That enhancement enables easier, more efficient and more hygienic handling, since both blood collection and subsequent analyses can be performed using the same sample vessel. In addition, Greiner eHealth Technologies (GeT) achieved a significant success in 2017 with the implementation of its digital, fully process-optimized system solution for preanalytical and postanalytical processes as a pilot project at the Styria General Hospital (Austria). By combining VACUETTE barcode tubes with a software solution, GeT plays an important part in optimizing preanalytical and postanalytical processes and ensuring enhanced data privacy, patient safety and quality. Thanks to the new and innovative NIMBUS and STARlet CX platforms of the BioScience division, all manual pipetting steps of the PapilloCheck HPV test can be automated and qualitative detection of HPV (human papillomavirus) is faster and more efficient. Together with technology provided by cooperation partner Nano3D Biosciences in Houston (USA), the CELL-STAR cell culture vessels with a cell-repellent service achieve particularly good results in the cultivation of 3D cell structures.
Greiner Bio-One has set itself ambitious goals for 2018. One focus will be on expanding its market position in Asia and North America. In addition, it plans to establish new distribution subsidiaries outside of Europe. The further expansion of services and product training courses for customers will also play a key role this year. Production capacity will be increased at several sites worldwide. In Frickenhausen (Germany), construction of a new high-bay warehouse is set to be completed and work is scheduled to begin on the second phase of extending the office and production areas.
www.gbo.com/preanalytics
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A USC research team identified 150 proteins affecting cell activity and brain development that contribute to mental disorders, including schizophrenia, bipolar condition and depression. It’s the first time these molecules, which are associated with the disrupted-in-schizophrenia 1 (DISC1) protein linked to mental disorders, have been identified. The scientists developed new tools involving stem cells to determine chemical reactions the proteins use to influence cell functions and nerve growth in people. “This moves science closer to opportunities for treatment for serious mental illness,” said Marcelo P. Coba, the study author and professor of psychiatry at the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. Schizophrenia affects less than 1 percent of the U.S. population, but has an outsized impact on disability, suicide and premature deaths. The DISC1 gene was linked to schizophrenia nearly 20 years ago. It controls how nerve cells called neurons develop, as well as how the brain matures. DISC1 also directs a network of signals across cells that can contribute to the disease. Scientists say errors in these chemical reactions contribute to schizophrenia. But the identity of proteins that DISC1 can regulate is poorly understood, prompting the USC researchers and colleagues from the State University of New York Downstate Medical Center to undertake the research. The challenge was to simulate conditions inside the human brain, Coba explained. Using stem cells, they conducted assays resembling habitat where DISC1 does its work. They then used gene editing to insert a molecular tag on DISC1, allowing them to extract it from brain cells and identify the proteins with which it associates. Identifying the proteins that interact with DISC1 in brain cells could lead to understanding how the risk factors for psychiatric diseases are connected to specific molecular functions, Coba explained. The discovery enables researchers to determine specific processes that differ in patients suffering from specific mental illnesses. This gives researchers specific trails to follow within cells from both healthy patients and those diagnosed with disorders. Schizophrenia is one of the top 15 leading causes of disability worldwide. People with schizophrenia live an average of nearly 29 years less than those without the disorder, according to the National Institutes of Mental Health (NIMH). The illness is often accompanied by conditions such as heart disease and diabetes, which contribute to the high premature mortality rate among people with schizophrenia. About 5 percent of people with schizophrenia die by suicide, a rate far greater than the general population, with the highest risk in the early stages of illness, according to the NIMH.
University of Southern California news.usc.edu/144238/usc-scientists-discover-schizophrenia-gene-roles-in-brain-development/
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A group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer. “We currently test for liver cancer using ultrasound and a blood protein marker called alpha fetoprotein,” says John Kisiel, M.D., a gastroenterologist at Mayo Clinic. “Unfortunately, these tests are not very sensitive for curable stage liver cancers, and most patients who need this testing do not have it easily available or [are] not able to receive it often enough to be effective.” Dr. Kisiel and his colleagues developed a simple blood test using abnormal DNA markers that are known to exist in liver cancer tissues. They were able to confirm that the abnormal DNA markers were present in the overwhelming majority of blood samples that came from people with primary liver cancers. Simultaneously, these markers were absent in healthy individuals and individuals with cirrhosis of the liver but no evidence of tumours on their clinical follow-up. “We were most excited that our DNA markers were able to detect more than 90 percent of patients with curable stage tumours,” says Dr. Kisiel. “This is the main reason why we think a DNA test will make difference, compared to currently available tests.” Dr. Kisiel says the next step will be to validate these markers in blood testing on much larger patient cohorts.
Mayo Clinic Cancer Center newsnetwork.mayoclinic.org/discussion/mayo-clinic-researchers-take-a-step-closer-to-developing-a-dna-test-for-liver-cancer/
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As the result of a six-year long research process, Fredrick R. Schumacher, PhD, a cancer epidemiology researcher at Case Western Reserve University School of Medicine, and an international team of more than 100 colleagues have identified 63 new genetic variations that could indicate higher risk of prostate cancer in men of European descent. The findings contain significant implications for which men may need to be regularly screened because of higher genetic risk of prostate cancer. The new findings also represent the largest increase in genetic markers for prostate cancer since they were first identified in 2006. The changes, known as genetic markers or SNPs ("snips"), occur when a single base in the DNA differs from the usual base at that position. There are four types of bases: adenine (A), thymine (T), guanine (G), and cytosine (C). The order of these bases determines DNA’s instructions, or genetic code. They can serve as a flag to physicians that a person may be at higher risk for a certain disease. Previously, about 100 SNPs were associated with increased risk of prostate cancer. There are three billion base pairs in the human genome; of these, 163 have now been associated with prostate cancer. One in seven men will be diagnosed with prostate cancer during their lifetimes. “Our findings will allow us to identify which men should have early and regular PSA screenings and these findings may eventually inform treatment decisions,” said Schumacher. PSA is a blood test used to screen for prostate cancer. It measures the amount of prostate-specific antigen (PSA) in the blood. PSA is a protein produced by both cancerous and noncancerous tissue in the prostate. Adding the 63 new SNPs to the 100 that are already known allows for the creation of a genetic risk score for prostate cancer. In the new study, the researchers found that men in the top one percent of the genetic risk score had a six-fold risk-increase of prostate cancer compared to men with an average genetic risk score. Those who had the fewest number of these SNPs, or a low genetic risk score, had the lowest likelihood of having prostate cancer. In a meta-analysis that combined both previous and new research data, Schumacher, with colleagues from Europe and Australia, examined DNA sequences of about 80,000 men with prostate cancer and about 60,000 men who didn’t have the disease. They found that men with cancer had a higher frequency of 63 different SNPs (also known as single nucleotide polymorphisms) that men without the disease did not have. Additionally, the more of these SNPs that a man has, the more likely he is to develop prostate cancer. The researchers estimate that there are about 500-1,000 genetic variants possibly linked to prostate cancer, not all of which have yet been identified. “We probably only need to know ten percent to twenty percent of these to provide relevant screening guidelines,” continued Schumacher, who is an associate professor in the Department of Population and Quantitative Health Sciences at Case Western Reserve School of Medicine. Currently, researchers don’t know which of the SNPs are the most predictive of increased prostate cancer risk. Schumacher and a number of colleagues are working to rank those most likely to be linked with prostate cancer, especially with aggressive forms of the disease that require surgery, as opposed to slowly developing versions that call for “watchful waiting” and monitoring. The research lays a foundation for determining who and how often men should undergo PSA tests. “In the future, your genetic risk score may be highly indicative of your prostate cancer risk, which will determine the intensity of PSA screening,” said Schumacher. “We will be working to determine that precise genetic risk score range that would trigger testing. Additionally, if you have a low score, you may need screening less frequently such as every 2-5 years.” A further implication of the findings of the new study is the possibility of precise treatments that do not involve surgery. “Someday it may be feasible to target treatments based on a patient’s prostate cancer genetic risk score,” said Schumacher.
Cape Western Reserve University School of Medicine casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1297&news_category=8
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High levels of cytoskeleton-associated protein 4 (CKAP4) have been identified in the blood of patients with lung cancer. In a novel study investigators found that CKAP4 levels were significantly higher in patients with lung cancer than in healthy individuals. They further determined that CKAP4 levels are already elevated in the blood of patients with stage I disease, making it a potential non-invasive diagnostic marker that could change current practices in the diagnosis and treatment of some types of lung cancer, including non-small-cell lung cancer and squamous cell carcinoma, and improve patient outcomes.
Lung cancer is the leading cause of cancer deaths in both men and women in the United States and worldwide. The disease is associated with a poor prognosis because most lung cancers are only diagnosed at an advanced stage.
"The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis," explained Yuichi Sato, PhD, Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan, who led the study. "We need better biomarkers for early diagnosis."
Current biomarkers for lung cancer include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), squamous cell carcinoma (SCC) antigen, and cytokeratin fragment (CYFRA) 21-1, but these are not sensitive enough to detect tumors early, according to co-investigator Ryo Nagashio, PhD, from the Kitasato University School of Allied Health Sciences. "The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer."
Researchers performed reverse-phase protein array analysis using a monoclonal antibody designated as KU-Lu-1 antibody on the blood of 271 lung cancer patients and 100 healthy individuals. KU-Lu-1 reacted only with tumor cells and tumor stromal fibroblasts in lung cancer tissues and not with normal lung tissues. Using immunoprecipitation and mass spectrometry, they confirmed that the KU-Lu-1 antibody recognized CKAP4 in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. In addition, a validation set consisting of samples from 100 patients with lung cancer and 38 healthy controls was also studied.
CKAP4 was recently identified as a receptor of Dickkopf1 (DKK1). Expressions of DKK1 and CKAP4 were frequently observed in tumor lesions of human pancreatic and lung cancers, and the simultaneous expression of both proteins in tumor tissues was inversely correlated with prognosis and relapse-free survival.
Across disease stages I-IV, the sensitivities of serum CEA, CYFRA, and SCCA are reported with 30 to 52, 17 to 82, and 24 to 39 percent, respectively. In this study, the sensitivity of serum CKAP4 was 81 percent in the training set and 69 percent in the validation set. These rates are higher than those of the current sero-diagnostic markers. Furthermore, the sensitivity of serum CKAP4 was also high even in stage I non-small-cell lung cancer and squamous cell carcinoma.
"The use of CKAP4 as a biomarker could change current practices regarding the treatment of lung cancer patients, and the diagnostic accuracies may be markedly improved by the combination of CKAP4 and conventional markers," concluded Dr. Sato.
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Mutations in the gene ANT1 may confer a risk for bipolar disorder through a complex interplay between serotonin and mitochondrial signalling in the brain. These two pathways have been separately implicated in bipolar disorder, but the link between levels of the neurotransmitter serotonin and mitochondrial dysfunction had not been established. Researchers at the RIKEN Center for Brain Science (CBS) in Japan now report that mitochondrial dysfunction affects the activity of serotonergic neurons in mice with mutations of ANT1. Mitochondria are the vital organelles that deliver energy to all cells and mitochondrial damage has been found, for example, in brain imaging of bipolar patients and in post-mortem brains. Roughly 20% of patients with mitochondrial disease also have bipolar disorder, a major psychiatric disease characterized by manic and depressive episodes. Altered serotonin functioning, on the other hand, seems to be involved in bipolar disorder because drugs that target serotonin levels can effectively treat the condition. "Our study suggests that mitochondrial dysfunction can alter activity of serotonergic neurons in bipolar disorder, and this is the first time these two lines of evidence have been linked," says Tadafumi Kato, research group leader at CBS. The study started by identifying ANT1 mutations in patients with bipolar disorder. Kato and colleagues then looked at mice lacking the ANT1 gene in the brain only. Compared with non-mutant mice, the mitochondria in these knockout mice could not retain calcium and had leakier pores. The ANT1-mutant mice also showed lower impulsivity in behaviour tests, and consistent with this, their brains showed elevated serotonin turnover. This hyper-serotonergic state is likely a result of a cascade of changes that starts with the loss of the ANT1 gene and the resulting dysfunctional mitochondria. Enhanced serotonergic activity may then further impair mitochondria in a vicious cycle. Serotonergic neurons were found to deteriorate in a brain area called the dorsal raphe, which is a region also affected in Parkinson’s disease–another condition that may have its roots in mitochondrial dysfunction. The ANT1 mutation does not cause bipolar disorder, says Kato, but is associated with elevated risk. The implication of this research is that emerging therapies for the underlying mitochondrial dysfunction could one day treat bipolar disorder more successfully than today’s variable serotonin-targeting drugs.
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R-Biopharm Group enters into collaboration with SSI (DK) in the field of tuberculosis diagnostics
, /in E-News /by 3wmediaR-Biopharm Group recently announced a collaborative agreement with SSI, focusing on discovery and development of novel diagnostic approaches for the detection of tuberculosis infection.
The development of new diagnostic assays in the area of infectious diseases is a priority for R-Biopharm, a company with 30 years of experience in providing testing solutions for Clinical Diagnostics and Food & Feed analysis. R-Biopharm Group operates in various countries including subsidiaries in the UK, USA, Italy, France, Latin America, Brazil, Spain, Belgium, Australia, India and China as well as by a worldwide extensive network of more than 120 distributors.
“This collaborative agreement creates an opportunity to work with the world-leading scientists and inventors of novel biomarkers and vaccines in the area of tuberculosis research. Our Infectious Diseases Team is inspired to join efforts for the development of novel diagnostics for the tuberculosis patients throughout the world. At R-Biopharm we are concerned about rising numbers of tuberculosis cases and escalation of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). In cooperation with Statens Serum Institute we will have the potential to transform the current underserved market of tuberculosis diagnostics and provide alternative solutions for the detection of TB infection,” said Dr. Ralf Dreher, CEO and Founder of R-Biopharm Group.
SSI is one of Denmark’s largest research institutions in the health sector with over a century of experience in research, development and manufacturing of biologics. Led by Professor Peter Andersen, the research and development team at SSI are at the forefront in the development of novel vaccines and diagnostic agents for major diseases affecting global health. The program has brought several novel vaccine candidates in clinical trial within TB and Chlamydia as well as provided the ground work for the current industry standard in diagnostic tests for tuberculosis infection (IGRAs).
“We are excited for our collaboration with R-Biopharm, a leading industry partner in the field of infectious disease diagnostics. As a government research organization under the ministry of health, industrial involvement is pivotal to get our projects from the lab out to the benefit of patients. The strong research base at R-Biopharm is a great match for the SSI team and has been a fruitful synergy,” said Prof. Peter Andersen, Executive Vice President, Center for Vaccine Research at Statens Serum Institute.
Under the agreement, R-Biopharm and SSI will collaborate on research and development and responsibility for the commercialization of potential products.
www.r-biopharm.com
Siemens, Hermes Pardini Group to create automated lab featuring the Atellica Solution
, /in E-News /by 3wmediaSiemens Healthineers is developing “The Enterprise Project” with the Hermes Pardini Group of Minas Gerais, Brazil. The Enterprise Project is the largest and most complex clinical analysis laboratory known to date and is expected to be capable of handling 110 million sample tubes per year upon completion. Siemens Healthineers, in collaboration with Inpeco, has designed and will deliver this fully automated multidisciplinary solution on an unprecedented scale, which will include at least 100 analysers—including more than 50 Atellica Solution clinical chemistry and immunoassay analysers from Siemens Healthineers, the largest IVD supplier in this project. The highly sophisticated solution will provide automation of clinical and operational workflow, from sample reception through testing to disposal. Sited in Vespasiano, Grande Belo Horizonte in Minas Gerais, the lab will occupy 3,500 square meters of floor space, will conduct operations 24 hours a day, and is expected to be fully operational during 2019.
“The automation track will be more than 330 meters long upon completion and will be used to automatically transport and distribute sample tubes to specific analysers that can run the specific type of test requested by clinicians,” said Guilherme Collares, Chef Operations Officer of the Hermes Pardini Group. “Unlike conventional laboratory set-ups, where sample tubes have to be moved manually between different analysers, our enterprise lab is designed to employ a ‘one-touch, one workflow’ concept to eliminate the need for manual interventions, ensure sample traceability, and reduce the turnaround time to results. The Enterprise Project also will rely on Atellica Process Manager, an IT solution that delivers a 3D view of the laboratory configuration, to enable operators to manage alerts, control instruments and reagent monitoring remotely, and see test progression in real time. Siemens Healthineers will implement the first Laboratory Control Room, which will centralize management and provide holistic visibility of operations in the central Vespasiano laboratory, and other Hermes Pardini satellite lab units in São Paulo, Rio de Janeiro, Goiania, and Belo Horizonte.
https://tinyurl.com/y9h4mtgm
Blood test for pregnant women can predict premature birth
, /in E-News /by 3wmediaA new blood test for pregnant women detects with 75-80 percent accuracy whether their pregnancies will end in premature birth. The technique can also be used to estimate a foetus’s gestational age — or the mother’s due date — as reliably as and less expensively than ultrasound.
Developed by a team of scientists led by researchers at Stanford University, the tests could help reduce problems related to premature birth, which affects 15 million infants worldwide each year. Until now, doctors have lacked a reliable way to predict whether pregnancies will end prematurely, and have struggled to accurately predict delivery dates for all types of pregnancies, especially in low-resource settings.
Stephen Quake, PhD, professor of bioengineering and of applied physics at Stanford, shares senior authorship with Mads Melbye, MD, visiting professor of medicine. The lead authors are former Stanford postdoctoral scholar Thuy Ngo, PhD, and Stanford graduate student Mira Moufarrej.
The tests measure the activity of maternal, placental and foetal genes by assessing maternal blood levels of cell-free RNA, tiny bits of the messenger molecule that carry the body’s genetic instructions to its protein-making factories. The team used blood samples collected during pregnancy to identify which genes gave reliable signals about gestational age and prematurity risk.
“We found that a handful of genes are very highly predictive of which women are at risk for preterm delivery,” said Melbye, who is also president and CEO of the Statens Serum Institute in Copenhagen. “I’ve spent a lot of time over the years working to understand preterm delivery. This is the first real, significant scientific progress on this problem in a long time.”
The gestational-age test was developed by studying a cohort of 31 Danish women who gave blood weekly throughout their pregnancies. The women all had full-term pregnancies. The scientists used blood samples from 21 of them to build a statistical model, which identified nine cell-free RNAs produced by the placenta that predict gestational age, and validated the model using samples from the remaining 10 women. The estimates of gestational age given by the model were accurate about 45 percent of the time, which is comparable to 48 percent accuracy for first-trimester ultrasound estimates.
This is the first real, significant scientific progress on this problem in a long time.
Measuring cell-free RNA in mothers’ blood also could provide a wealth of new information about foetal growth, Ngo said. “This gives a super-high resolution view of pregnancy and human development that no one’s ever seen before,” she said. “It tells us a lot about human development in normal pregnancy.”
To figure out how to predict preterm birth, the researchers used blood samples from 38 American women who were at risk for premature delivery because they had already had early contractions or had given birth to a preterm baby before. These women each gave one blood sample during the second or third trimester of their pregnancies. Of this group, 13 delivered prematurely, and the remaining 25 delivered at term. The scientists found that levels of cell-free RNA from seven genes from the mother and the placenta could predict which pregnancies would end early.
“It’s mostly maternal genes,” Moufarrej said, noting that the genes that predict prematurity are different than those that give information about gestational age. “We think it’s mom sending a signal that she’s ready to pull the ripcord.”
The scientists need to validate the new tests in larger cohorts of pregnant women before they can be made available for widespread use.
The biological mechanism behind preterm birth is still a mystery, but the scientists plan to investigate the roles of the genes that signal prematurity to better understand why it happens. They also hope to identify targets for drugs that could delay premature birth.
Other Stanford authors of the paper are graduate student Keli Liu; postdoctoral scholar Joan Camunas-Soler, PhD; research affiliates Wenying Pan, PhD, Jennifer Okamoto and Norma Neff, PhD; senior research scientist Ronald Wong; Robert Tibshirani, PhD, professor of biomedical data science and of statistics; Gary Shaw, DrPH, professor of pediatrics; and David Stevenson, MD, professor of pediatrics.
This gives a super-high resolution view of pregnancy and human development
Scientists from the Statens Serum Institute in Copenhagen, the University of Pennsylvania School of Medicine and the University of Alabama-Birmingham also contributed to the study.
Quake, Tibshirani, Shaw and Stevenson are members of Stanford Bio-X; Tibshirani, Shaw and Stevenson are members of the Stanford Child Health Research Institute; Quake and Tibshirani are members of the Stanford Cancer Institute; Stevenson is an affiliate of the Stanford Woods Institute for the Environment; and Quake is a member of the Stanford Cardiovascular Institute, Stanford ChHEM-H and the Stanford Neurosciences Institute.
The research was funded by the Bill and Melinda Gates Foundation, the March of Dimes Prematurity Research Center at Stanford University, the March of Dimes Prematurity Initiative Grant at the University of Pennsylvania and the Chan Zuckerberg Biohub, of which Quake is co-president.
The Chan Zuckerberg Biohub has submitted a patent application for the new technology.
Stanford’s departments of Bioengineering, Applied Physics and Pediatrics also supported the work. The Department of Bioengineering is jointly operated by the schools of Medicine and of Engineering.
Stanford Medicine
med.stanford.edu/news/all-news/2018/06/blood-test-for-pregnant-women-can-predict-premature-birth.html
Early Indicators of Bone Loss After Hip Replacement Discovered
, /in E-News /by 3wmediaHip replacements relieve pain and restore mobility for hundreds of thousands of patients in the United States each year, but of the more than 400,000 hip replacements performed in the U.S. annually, about 10 percent will fail within 10 to 15 years. One main cause of this failure — which results in a need for a second hip replacement surgery (known as a revision surgery) — is the destruction of bone tissue around the replacement joint, a condition called osteolysis, which may cause the joint to loosen.
Now a research team at Rush University Medical Center has identified a pair of biomarkers that indicate which patients are likely to develop osteolysis.
The discovery could lead to tests that would enable surgeons to identify those patients in advance and adjust post-operative monitoring routines for them. It even might lead to treatments to prevent osteolysis in these patients.
“We are hopeful that early biomarkers for implant loosening will alert surgeons to be especially vigilant in their follow-up of at-risk patients and may eventually lead to treatments delaying or avoiding the need for revision surgery,” said the paper’s senior author D. Rick Sumner, PhD, chairperson of the Department of Cell & Molecular Medicine in Rush Medical College and the Mary Lou Bell McGrew Presidential Professor for Medical Research.
With the U.S. population aging, many individuals remaining very active late in life and others becoming heavier, hip replacements are projected to increase by 174 percent by 2030, with a projected 137 percent increase in the number of hip revision surgeries to fix or replace the failed implant over the same time period.
“We need to find effective strategies to handle this demand. These joints need to last, if possible, for the rest of a patient’s life,” said Joshua Jacobs, MD, a co-investigator on the study. Jacobs is Rush University’s vice provost for research and the William A. Hark, MD/Susanne G. Swift Professor and chairperson of the Rush Department of Orthopedic Surgery.
For their study, Sumner and his colleagues took what he calls “a candidate protein approach.” They drew on a previous review of medical literature they had conducted, which identified 40 possible biomarkers of future osteolysis development.
They divided the markers into four groups based on their likelihood to predict osteolysis and focused on the two groups that were most likely. The researchers winnowed the field of candidate proteins by eliminating markers found in blood rather than urine and those for which tests weren’t readily available.
Two combined biomarkers provided strongest indication of risk
Ultimately they tested for the presence of seven biomarkers and compared findings to the medical history of the patients – 16 of whom eventually had developed osteolysis. A biostatisican on the team then conducted an analysis to determine which combinations of the biomarkers correlated most with the osteolysis development.
“We looked at each marker independently, but none of them worked that well by themselves. Then he looked at panels of markers,” Sumner explained. “When we did that, we found we got a much better discrimination between patients that developed osteolysis and those that did not.”
The analysis found that a higher than normal levels of the connective tissue protein alpha CTX (a marker for bone resorption) and the immune response protein interleukin 6 (a marker of inflammation) were highly accurate in identifying patients at risk for osteolysis. The combination was detectable in patients up to six years before they were diagnosed with osteolysis.
Rush University
www.rush.edu/news/press-releases/early-indicators-bone-loss-after-hip-replacement-discovered
Greiner Bio-One looks back on successful year
, /in E-News /by 3wmediaGreiner Bio-One had a successful business year in 2017, further reinforcing its market position thanks to strong growth, new sites and innovative product solutions. The takeover of its long-standing, exclusive distribution partners VACUETTE España and VACUETTE Portugal in March 2017 has enabled greater proximity to customers and targeted market cultivation. As a result of that takeover, Greiner Bio-One now has its own subsidiaries on two further key markets in Europe. In addition, the headquarters in Kremsmünster were expanded and an investment was made in a warehouse facility at the site in Hungary.
In July 2017, Greiner Bio-One acquired 90% of shares in Vigmed Holding AB, a listed technology and trade company based in Helsingborg, Sweden. That has enabled I.V. catheters with a safety mechanism to be added to the Preanalytics safety products range. Another innovation on the market is the MiniCollect Complete tube – a version in which the MiniCollect standard tube is irreversibly assembled in a carrier tube. That enhancement enables easier, more efficient and more hygienic handling, since both blood collection and subsequent analyses can be performed using the same sample vessel.
In addition, Greiner eHealth Technologies (GeT) achieved a significant success in 2017 with the implementation of its digital, fully process-optimized system solution for preanalytical and postanalytical processes as a pilot project at the Styria General Hospital (Austria). By combining VACUETTE barcode tubes with a software solution, GeT plays an important part in optimizing preanalytical and postanalytical processes and ensuring enhanced data privacy, patient safety and quality.
Thanks to the new and innovative NIMBUS and STARlet CX platforms of the BioScience division, all manual pipetting steps of the PapilloCheck HPV test can be automated and qualitative detection of HPV (human papillomavirus) is faster and more efficient. Together with technology provided by cooperation partner Nano3D Biosciences in Houston (USA), the CELL-STAR cell culture vessels with a cell-repellent service achieve particularly good results in the cultivation of 3D cell structures.
Greiner Bio-One has set itself ambitious goals for 2018. One focus will be on expanding its market position in Asia and North America. In addition, it plans to establish new distribution subsidiaries outside of Europe. The further expansion of services and product training courses
for customers will also play a key role this year. Production capacity will be increased at several sites worldwide. In Frickenhausen (Germany), construction of a new high-bay warehouse is set to be completed and work is scheduled to begin on the second phase of extending the office and production areas. www.gbo.com/preanalytics
Scientists discover schizophrenia gene roles in brain development
, /in E-News /by 3wmediaA USC research team identified 150 proteins affecting cell activity and brain development that contribute to mental disorders, including schizophrenia, bipolar condition and depression.
It’s the first time these molecules, which are associated with the disrupted-in-schizophrenia 1 (DISC1) protein linked to mental disorders, have been identified. The scientists developed new tools involving stem cells to determine chemical reactions the proteins use to influence cell functions and nerve growth in people.
“This moves science closer to opportunities for treatment for serious mental illness,” said Marcelo P. Coba, the study author and professor of psychiatry at the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC.
Schizophrenia affects less than 1 percent of the U.S. population, but has an outsized impact on disability, suicide and premature deaths.
The DISC1 gene was linked to schizophrenia nearly 20 years ago. It controls how nerve cells called neurons develop, as well as how the brain matures. DISC1 also directs a network of signals across cells that can contribute to the disease. Scientists say errors in these chemical reactions contribute to schizophrenia.
But the identity of proteins that DISC1 can regulate is poorly understood, prompting the USC researchers and colleagues from the State University of New York Downstate Medical Center to undertake the research. The challenge was to simulate conditions inside the human brain, Coba explained.
Using stem cells, they conducted assays resembling habitat where DISC1 does its work. They then used gene editing to insert a molecular tag on DISC1, allowing them to extract it from brain cells and identify the proteins with which it associates.
Identifying the proteins that interact with DISC1 in brain cells could lead to understanding how the risk factors for psychiatric diseases are connected to specific molecular functions, Coba explained. The discovery enables researchers to determine specific processes that differ in patients suffering from specific mental illnesses.
This gives researchers specific trails to follow within cells from both healthy patients and those diagnosed with disorders.
Schizophrenia is one of the top 15 leading causes of disability worldwide. People with schizophrenia live an average of nearly 29 years less than those without the disorder, according to the National Institutes of Mental Health (NIMH).
The illness is often accompanied by conditions such as heart disease and diabetes, which contribute to the high premature mortality rate among people with schizophrenia. About 5 percent of people with schizophrenia die by suicide, a rate far greater than the general population, with the highest risk in the early stages of illness, according to the NIMH.
University of Southern California
news.usc.edu/144238/usc-scientists-discover-schizophrenia-gene-roles-in-brain-development/
Researchers take a step closer to developing a DNA test for liver cancer
, /in E-News /by 3wmediaA group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer.
“We currently test for liver cancer using ultrasound and a blood protein marker called alpha fetoprotein,” says John Kisiel, M.D., a gastroenterologist at Mayo Clinic. “Unfortunately, these tests are not very sensitive for curable stage liver cancers, and most patients who need this testing do not have it easily available or [are] not able to receive it often enough to be effective.”
Dr. Kisiel and his colleagues developed a simple blood test using abnormal DNA markers that are known to exist in liver cancer tissues. They were able to confirm that the abnormal DNA markers were present in the overwhelming majority of blood samples that came from people with primary liver cancers. Simultaneously, these markers were absent in healthy individuals and individuals with cirrhosis of the liver but no evidence of tumours on their clinical follow-up.
“We were most excited that our DNA markers were able to detect more than 90 percent of patients with curable stage tumours,” says Dr. Kisiel. “This is the main reason why we think a DNA test will make difference, compared to currently available tests.” Dr. Kisiel says the next step will be to validate these markers in blood testing on much larger patient cohorts.
Mayo Clinic Cancer Center
newsnetwork.mayoclinic.org/discussion/mayo-clinic-researchers-take-a-step-closer-to-developing-a-dna-test-for-liver-cancer/
Dozens of new gene changes that point to elevated of prostate cancer risk
, /in E-News /by 3wmediaAs the result of a six-year long research process, Fredrick R. Schumacher, PhD, a cancer epidemiology researcher at Case Western Reserve University School of Medicine, and an international team of more than 100 colleagues have identified 63 new genetic variations that could indicate higher risk of prostate cancer in men of European descent. The findings contain significant implications for which men may need to be regularly screened because of higher genetic risk of prostate cancer. The new findings also represent the largest increase in genetic markers for prostate cancer since they were first identified in 2006.
The changes, known as genetic markers or SNPs ("snips"), occur when a single base in the DNA differs from the usual base at that position. There are four types of bases: adenine (A), thymine (T), guanine (G), and cytosine (C). The order of these bases determines DNA’s instructions, or genetic code. They can serve as a flag to physicians that a person may be at higher risk for a certain disease. Previously, about 100 SNPs were associated with increased risk of prostate cancer. There are three billion base pairs in the human genome; of these, 163 have now been associated with prostate cancer.
One in seven men will be diagnosed with prostate cancer during their lifetimes.
“Our findings will allow us to identify which men should have early and regular PSA screenings and these findings may eventually inform treatment decisions,” said Schumacher. PSA is a blood test used to screen for prostate cancer. It measures the amount of prostate-specific antigen (PSA) in the blood. PSA is a protein produced by both cancerous and noncancerous tissue in the prostate.
Adding the 63 new SNPs to the 100 that are already known allows for the creation of a genetic risk score for prostate cancer. In the new study, the researchers found that men in the top one percent of the genetic risk score had a six-fold risk-increase of prostate cancer compared to men with an average genetic risk score. Those who had the fewest number of these SNPs, or a low genetic risk score, had the lowest likelihood of having prostate cancer.
In a meta-analysis that combined both previous and new research data, Schumacher, with colleagues from Europe and Australia, examined DNA sequences of about 80,000 men with prostate cancer and about 60,000 men who didn’t have the disease. They found that men with cancer had a higher frequency of 63 different SNPs (also known as single nucleotide polymorphisms) that men without the disease did not have. Additionally, the more of these SNPs that a man has, the more likely he is to develop prostate cancer.
The researchers estimate that there are about 500-1,000 genetic variants possibly linked to prostate cancer, not all of which have yet been identified. “We probably only need to know ten percent to twenty percent of these to provide relevant screening guidelines,” continued Schumacher, who is an associate professor in the Department of Population and Quantitative Health Sciences at Case Western Reserve School of Medicine.
Currently, researchers don’t know which of the SNPs are the most predictive of increased prostate cancer risk. Schumacher and a number of colleagues are working to rank those most likely to be linked with prostate cancer, especially with aggressive forms of the disease that require surgery, as opposed to slowly developing versions that call for “watchful waiting” and monitoring.
The research lays a foundation for determining who and how often men should undergo PSA tests. “In the future, your genetic risk score may be highly indicative of your prostate cancer risk, which will determine the intensity of PSA screening,” said Schumacher. “We will be working to determine that precise genetic risk score range that would trigger testing. Additionally, if you have a low score, you may need screening less frequently such as every 2-5 years.” A further implication of the findings of the new study is the possibility of precise treatments that do not involve surgery. “Someday it may be feasible to target treatments based on a patient’s prostate cancer genetic risk score,” said Schumacher.
Cape Western Reserve University School of Medicine
casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1297&news_category=8
New biomarker identified for early diagnosis of lung cancer
, /in E-News /by 3wmediaHigh levels of cytoskeleton-associated protein 4 (CKAP4) have been identified in the blood of patients with lung cancer. In a novel study investigators found that CKAP4 levels were significantly higher in patients with lung cancer than in healthy individuals. They further determined that CKAP4 levels are already elevated in the blood of patients with stage I disease, making it a potential non-invasive diagnostic marker that could change current practices in the diagnosis and treatment of some types of lung cancer, including non-small-cell lung cancer and squamous cell carcinoma, and improve patient outcomes.
Lung cancer is the leading cause of cancer deaths in both men and women in the United States and worldwide. The disease is associated with a poor prognosis because most lung cancers are only diagnosed at an advanced stage.
"The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis," explained Yuichi Sato, PhD, Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan, who led the study. "We need better biomarkers for early diagnosis."
Current biomarkers for lung cancer include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), squamous cell carcinoma (SCC) antigen, and cytokeratin fragment (CYFRA) 21-1, but these are not sensitive enough to detect tumors early, according to co-investigator Ryo Nagashio, PhD, from the Kitasato University School of Allied Health Sciences. "The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer."
Researchers performed reverse-phase protein array analysis using a monoclonal antibody designated as KU-Lu-1 antibody on the blood of 271 lung cancer patients and 100 healthy individuals. KU-Lu-1 reacted only with tumor cells and tumor stromal fibroblasts in lung cancer tissues and not with normal lung tissues. Using immunoprecipitation and mass spectrometry, they confirmed that the KU-Lu-1 antibody recognized CKAP4 in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. In addition, a validation set consisting of samples from 100 patients with lung cancer and 38 healthy controls was also studied.
CKAP4 was recently identified as a receptor of Dickkopf1 (DKK1). Expressions of DKK1 and CKAP4 were frequently observed in tumor lesions of human pancreatic and lung cancers, and the simultaneous expression of both proteins in tumor tissues was inversely correlated with prognosis and relapse-free survival.
Across disease stages I-IV, the sensitivities of serum CEA, CYFRA, and SCCA are reported with 30 to 52, 17 to 82, and 24 to 39 percent, respectively. In this study, the sensitivity of serum CKAP4 was 81 percent in the training set and 69 percent in the validation set. These rates are higher than those of the current sero-diagnostic markers. Furthermore, the sensitivity of serum CKAP4 was also high even in stage I non-small-cell lung cancer and squamous cell carcinoma.
"The use of CKAP4 as a biomarker could change current practices regarding the treatment of lung cancer patients, and the diagnostic accuracies may be markedly improved by the combination of CKAP4 and conventional markers," concluded Dr. Sato.
EurekAlert
www.eurekalert.org/pub_releases/2018-05/e-nbi050718.php
Mutation links bipolar disorder to mitochondrial disease
, /in E-News /by 3wmediaMutations in the gene ANT1 may confer a risk for bipolar disorder through a complex interplay between serotonin and mitochondrial signalling in the brain. These two pathways have been separately implicated in bipolar disorder, but the link between levels of the neurotransmitter serotonin and mitochondrial dysfunction had not been established. Researchers at the RIKEN Center for Brain Science (CBS) in Japan now report that mitochondrial dysfunction affects the activity of serotonergic neurons in mice with mutations of ANT1.
Mitochondria are the vital organelles that deliver energy to all cells and mitochondrial damage has been found, for example, in brain imaging of bipolar patients and in post-mortem brains. Roughly 20% of patients with mitochondrial disease also have bipolar disorder, a major psychiatric disease characterized by manic and depressive episodes. Altered serotonin functioning, on the other hand, seems to be involved in bipolar disorder because drugs that target serotonin levels can effectively treat the condition. "Our study suggests that mitochondrial dysfunction can alter activity of serotonergic neurons in bipolar disorder, and this is the first time these two lines of evidence have been linked," says Tadafumi Kato, research group leader at CBS.
The study started by identifying ANT1 mutations in patients with bipolar disorder. Kato and colleagues then looked at mice lacking the ANT1 gene in the brain only. Compared with non-mutant mice, the mitochondria in these knockout mice could not retain calcium and had leakier pores. The ANT1-mutant mice also showed lower impulsivity in behaviour tests, and consistent with this, their brains showed elevated serotonin turnover. This hyper-serotonergic state is likely a result of a cascade of changes that starts with the loss of the ANT1 gene and the resulting dysfunctional mitochondria. Enhanced serotonergic activity may then further impair mitochondria in a vicious cycle.
Serotonergic neurons were found to deteriorate in a brain area called the dorsal raphe, which is a region also affected in Parkinson’s disease–another condition that may have its roots in mitochondrial dysfunction. The ANT1 mutation does not cause bipolar disorder, says Kato, but is associated with elevated risk. The implication of this research is that emerging therapies for the underlying mitochondrial dysfunction could one day treat bipolar disorder more successfully than today’s variable serotonin-targeting drugs.
EurekAlert
www.eurekalert.org/pub_releases/2018-06/r-mlb060818.php