An opportunity exists to require the rights to a real time PCR test for thirteen oncogenic HPV types (Jenkins et al, J Virol Methods 2013).
Interested parties should contact: not later than 01.09.2017
Lawyer Maria Torvund
Uniongata 18
3732 Skien
Norway
Tel: +47 35 53 20 00
Fax: +47 35 53 20 01
advokat@mariatorvund.no
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
Van Andel Research Institute (VARI) announced that the work of its scientists is featured in 27 papers focused on the output of The Cancer Genome Atlas (TCGA).
The findings are the result of a global scientific collaboration and mark the culmination of TCGA, a multi-institutional, joint effort between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to develop a comprehensive scientific resource for better categorizing cancer. The more than decade-long initiative is the most in-depth undertaking of its kind, spanning 10,000 tumours across 33 cancer types.
“TCGA’s findings have greatly deepened our molecular understanding of the major cancer types,” said Peter W. Laird, Ph.D., a professor at VARI who led the DNA methylation analysis for TCGA Research Network and who is senior author on two of today’s papers. “It is our hope that these publications will serve as a guide for scientists who plan to harness TCGA’s robust data to develop new, more personalized methods of patient care.”
This research, which represents the project’s capstone, joins dozens of other papers that have been published since TCGA’s inception in 2005. Collectively, they provide a highly detailed description of molecular changes occurring in all major human cancers. The use of this molecular atlas is rapidly expanding, with more than 1,000 publications citing TCGA data in 2017 alone.
TCGA data may be accessed through the National Cancer Institute’s Genomic Data Commons Data Portal (portal.gdc.cancer.gov).
Along with Laird, VARI Assistant Professor Hui Shen, Ph.D., contributed to many of today’s papers, summaries of which may be found below. Shen also is one of six experts who authored retrospectives on TCGA’s legacy, which also were published.
A full list of papers may be found at www.cell.com/consortium/pancanceratlas.
Van Andel Institutewww.vai.org/news-release-4-5-2018/
The research carried out at Queen Mary University of London, University of Exeter and Vanderbilt University could lead to the development of novel treatments for both rare and common forms of diabetes.
In addition to the more common forms of diabetes (type 1 or type 2), in about 1-2 per cent of cases diabetes is due to a genetic disorder, known as maturity onset diabetes of the young (MODY). A defective gene typically affects the function of insulin-producing cells in the pancreas, known as beta cells.
The research team studied the unique case of a family where several individuals suffer from diabetes, while other family members had developed insulin-producing tumours in their pancreas. These tumours, known as insulinomas, typically cause low blood sugar levels, in contrast to diabetes which leads to high blood sugar levels.
Lead author Professor Márta Korbonits from Queen Mary’s William Harvey Research Institute said: “We were initially surprised about the association of two apparently contrasting conditions within the same families – diabetes which is associated with high blood sugar and insulinomas associated with low blood sugar. Our research shows that, surprisingly, the same gene defect can impact the insulin-producing beta cells of the pancreas to lead to these two opposing medical conditions.”
The team also observed that males were more prone to developing diabetes, while insulinomas were more commonly found in females, but the reasons behind this difference are as yet unknown.
Professor Korbonits added: “One exciting avenue to explore will be seeing if we can use this finding to uncover new ways to help regenerate beta cells and treat the more common forms of diabetes.”
The researchers identified a genetic disorder in a gene called MAFA, which controls the production of insulin in beta cells. Unexpectedly, this gene defect was present in both the family members with diabetes and those with insulinomas, and was also identified in a second, unrelated family with the same unusual dual picture.
This is the first time a defect in this gene has been linked with a disease. The resultant mutant protein was found to be abnormally stable, having a longer life in the cell, and therefore significantly more abundant in the beta cells than its normal version.
First author Dr Donato Iacovazzo from Queen Mary’s William Harvey Research Institute added: “We believe this gene defect is critical in the development of the disease and we are now performing further studies to determine how this defect can, on the one hand, impair the production of insulin to cause diabetes, and on the other, cause insulinomas.”
Queen Mary University of Londonwww.qmul.ac.uk/media/news/2018/smd/diabetes-gene-found-that-causes-low-and-high-blood-sugar-levels-in-the-same-family.html
Rates of inherited mutations in genes other than BRCA1/2 are twice as high in breast cancer patients who have had a second primary cancer – including, in some cases, different types of breast cancer – compared to patients who have only had a single breast cancer. But the rates of these mutations were still found to be low overall, meaning it’s difficult to assess whether and how these individual mutations may drive the development of cancer. The study from the Basser Center for BRCA in the Abramson Cancer Center of the University of Pennsylvania also investigated the use of polygenic risk scores – which have recently been added to some commercial clinical multiplex genetic testing panels. Kara N. Maxwell, MD, PhD, an instructor of Hematology-Oncology and the study’s lead author, presented the findings at the 2018 American Society of Clinical Oncology Annual.
Genetic testing can help identify patients have a genetic predisposition that puts them at risk for developing cancer. Recently, new therapies called PARP inhibitors have been FDA approved to specifically target cancers caused by certain mutations – such as BRCA1/2, which carry a lifetime breast cancer risk of as much as 85 percent and 50 percent for ovarian cancer, as well as higher risks of pancreatic, prostate and other cancers.
“We need to gain a better understanding of why patients who have multiple cancers may be susceptible to them, and that work needs to go beyond the common genes we’re already been looking at,” Maxwell said.
The team – led by Susan M. Domchek, MD, executive director of the Basser Center for BRCA, and Katherine L. Nathanson, MD, deputy director of the Abramson Cancer Center, specifically looked at patients who did not have a BRCA1/2 mutation and tested them for a panel of 15 different genetic mutations. They evaluated 891 patients who had a second primary cancer – breast or otherwise – after initial breast cancer and compared them to 1,928 who only had a single breast cancer. About eight percent of patients who had second primary cancers had mutations, compared to just four percent of patients from the single cancer cohort. The current threshold for whether or not genetic testing is recommended is five percent.
“Our data show that patients who have had multiple primary cancers should undergo genetic testing, and likely this holds true for a number of other types of second cancer,” Maxwell said. “However, the overall numbers are still low, which shows the level of uncertainty that still exists and highlights the need for further research.”
The research also evaluated polygenic risk scores, a somewhat controversial metric recently added to some commercial clinical multiplex genetic testing panels. Polygenic risk scores are determined by how many single nucleotide polymorphisms (SNPs) a person has. SNPs are common variants with smaller effect sizes, and if a patient has multiple of certain SNPs, they may be at a similar increased for cancer a as patients with a single rare mutation.
“Our study does not provide strong evidence of higher polygenic risk scores in patients with more than one breast cancer,” but many more patients will need to be studied to confirm this,” Maxwell said.
Penn Medicinewww.pennmedicine.org/news/news-releases/2018/june/beyond-brca-examining-links-between-breast-cancer-second-primary-cancer-inherited-genetic-mutations
In October 2016, researchers at the Aga Khan University’s microbiology laboratory spotted a number of unusual organisms in blood samples from Hyderabad. Blood culture tests from the city contained a novel strain of typhoid that had developed resistance to an unprecedented range of antibiotics.
Over the next few months, several similar cases were detected from the city pointing to an outbreak of a form of the disease that would be especially difficult to treat.
The research team, led by Pofessor Rumina Hasan, acted quickly to alert local government, the National Institutes of Health and the World Health Organization to this development. They also contacted the UK-based Wellcome Sanger Institute to explore the genetic cause behind the emergence of this extensively drug-resistant (XDR) typhoid strain.
“This was the world’s first outbreak of XDR typhoid,” said Professor Zahra Hasan of the department of pathology and laboratory medicine. “Understanding this new threat required high-level genome sequencing which would enable us to analyse the molecular blueprint of this new form of typhoid.”
Over the next six months, the research team collaborated with experts at the Wellcome Sanger Institute to jointly analyse over 100 DNA samples which resulted in a striking finding. The typhoid bacteria had acquired a DNA molecule through a plasmid from a bacterium commonly found in contaminated water and food, making it resistant to the majority of available medications .
“We used to think that we had a complete picture of the typhoid ‘puzzle’,” said Dr Sadia Shakoor, assistant professor in pathology and laboratory medicine at AKU. “Together with our partners, we’ve found a missing piece that affects how we diagnose and treat the most complex strains of the disease.”
Since patients with XDR typhoid do not respond to commonly prescribed antibiotics, blood culture tests have become an even more important tool for physicians, according to Dr Shakoor. Not only do these tests enable early detection but they also highlight the type of typhoid being tackled that affects the choice of antibiotic.
“There are currently three antibiotics available to treat XDR typhoid,” Dr Shakoor stated. “These drugs are expensive and we must only prescribe them when needed. Otherwise, bacteria could develop resistance to the only medications we have left.”
Beyond resistance, researchers also warn of the risk of the disease spreading since every patient is a potential ‘disease carrier’. The likelihood of the proliferation of the disease is especially high in developing countries where poor sanitation facilities result in the contamination of drinking water with sewage containing the typhoid bacteria.
Aga Khan Universitywww.aku.edu/news/Pages/News_Details.aspx?nid=NEWS-001521
Investigators at The Feinstein Institute for Medical Research discovered dozens of new genetic variations associated with a person’s general cognitive ability. The findings have the potential to help researchers develop more targeted treatment for cognitive and memory disorders.
“For the first time, we were able to use genetic information to point us towards specific drugs that might aid in cognitive disorders of the brain, including Alzheimer’s disease, schizophrenia and attention deficit hyperactivity disorder,” said Todd Lencz, PhD, senior author of the study and professor at the Feinstein Institute and the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell.
In the largest peer-reviewed study of its kind, an international team of 65 scientists, led by Dr. Lencz, studied the genomes of more than 100,000 individuals who had their brain function measured by neuropsychological tests. These data were then combined with genomes from 300,000 people measured for the highest level of education achieved, which serves as an estimate for cognitive ability, or how the brain acquires knowledge.
While profiling cognitive ability, researchers also discovered a genetic overlap with longevity. They found when examining an individual’s family that a genetic predisposition towards higher cognitive ability was associated with longer lifespan. A new genetic overlap between cognitive ability and risk for autoimmune disease was also identified.
This study appears less than a year after Dr. Lencz and his colleagues published a similar, smaller study that was only able to identify a few key genes associated with cognitive ability.
“The field of genomics is growing by leaps and bounds,” Dr. Lencz said. “Because the number of genes we can discover is a direct function of the sample size available, further research with additional samples is likely to provide even more insight into how our genes play a role in cognitive ability.”
Feinstein Institute – Northwell Healthhttps://tinyurl.com/y8649b9o
A high-sensitive blood test can aid concussed hockey players when it might be safe to return to play. In a study, researchers at Sahlgrenska Academy has identified a superior blood-based biomarker for assessing subtle brain injury.
"This could serve as an objective test a long side clinical evaluation to whether a player is fit to return to playing. Currently, we lack an objective test like this", says Dr. Pashtun Shahim, lead author of the article.
The study entails yet another step forward in the research that has been carried out in Gothenburg for several years, with focus on sports-related concussions. This time it included all Swedish ice hockey teams that played in the highest division on the men’s side, SHL, during three seasons 2012-2015. Hockey clubs from Luleå HF in the north of Sweden to Rögle BK in the south were involved in the work.
In total, 288 players were included, of which 105 suffered a concussion during the seasons in question. From 87 of these players, blood samples were taken 1, 12, 36 and 144 hours (six days) after the concussion. A fifth sample was taken at the time when the person was determined fit to return to unrestricted competition.
The purpose of the study was to compare concentrations in the blood of known biomarkers for concussion, both directly after the event and over a period of time. The results show that it was the levels of the protein neurofilament light (NfL) that had the clearest connection to the severity of concussion, measured as the number of days it took for players to return to play.
"The strength of this study is that we longitudinally followed how these biomarkers are released and cleared from the blood. What we observed was that NfL was released within an hour after the concussion, and then it increased over time in players who had prolonged symptoms", Pashtun Shahim explains.
The levels of the other biomarkers that were studied (tau, S100B and neuron-specific enolase, NSE) decreased quickly and could thereby not indicate how injured the players were after 7-10 days, a time point many players returned to play in the study.
"Currently the duration of players’ symptoms determines when it is safe to play again. The finding that serum NfL concentrations correlate with the duration of post-concussive symptoms or return to play, implicates that serum NfL might serve as an objective test of when it is safe to return to play. It is important to protect the players from developing long-term symptoms by avoiding premature return to play. Suffering additional concussion, especially when the current post-concussion symptoms are not fully resolved might have long-term consequences", says Pashtun Shahim.
"There is no need for a biomarker in order to make a diagnosis of concussion, it is a clinical diagnosis that is based on the patient’s symptoms", he continues. "What we are really after is a prognostic biomarker that helps the physicians determine which players or patients might be at increased risk of developing persistent post-concussive symptoms, and thereby adjust the level of rest and care for these players."
University of Gothenburgwww.gu.se/english/about_the_university/news-calendar/News_detail//a-high-sensitive-blood-test-when-it-is-safe-to-return-to-play-after-a-sports-related-concussion.cid1564034
A report describes a new simple molecular test to detect chromosomal abnormalities — biomarkers known as telomere fusions–in pancreatic tumour specimens and pancreatic cyst fluids. This assay may help predict the presence of high-grade or invasive pancreatic cancers requiring surgical intervention.
More sophisticated imaging of the pancreas has led to increased detection of presymptomatic lesions. The detection of telomere fusions has the potential to help physicians determine whether these lesions have a high likelihood of developing into pancreatic cancer requiring surgical resection or are more likely to be benign and can be followed by “watchful waiting.”
“Clinicians rely on international consensus guidelines to help manage patients with pancreatic cancer precursor lesions such as intraductal papillary mucinous neoplasms (IPMNs). These guidelines are useful but pancreatic imaging does not provide sufficient information about the neoplastic nature of a pancreatic cyst. Better characterization of pancreatic cysts could allow more patients with worrisome cysts to continue with surveillance, avoiding the morbidity and risks related to pancreatic surgery,” explained Michael Goggins, MD, Sol Goldman Professor of Pancreatic Cancer Research, Departments of Pathology, Surgery, and Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine (Baltimore).
Telomeres are regions of repetitive nucleotide sequences found at the ends of chromosomes that, under normal circumstances, keep the chromosome intact. When telomeres lose most or all of their telomere repeat sequences, the ends can fuse, leading to cell death or chromosomal instability. “This is a major mechanism that contributes to the progression of many precancerous neoplasms to invasive cancers,” said Dr. Goggins. “Telomere fusions can serve as a marker for predicting the presence of high-grade dysplasia and/or invasive cancer.”
In this report, investigators describe a PCR-based assay to detect telomere fusions in samples of pancreatic tumour or cyst fluid. The assay incorporates two rounds of PCR with the second round using a telomere repeat probe to detect the fusions.
The researchers analysed tissues from IPMN tumour samples taken from patients undergoing resection, surgical cyst fluid samples, and normal pancreas. IPMNs are the most common type of pancreatic neoplastic cysts. They are characterized by the papillary proliferation of mucin-producing epithelial cells and cystic dilatation of the main or branch pancreatic duct.
This telomere fusion assay was able to identify telomere fusions in more than half of the pancreatic cell lines. Telomere fusions were often detected in tumours with high-grade dysplasia (containing more abnormal cells). Telomere fusions were not found in normal pancreas or samples with low-grade dysplasia.
Similar findings were seen in analyses of cyst fluid, in which the presence of telomere fusions raised the likelihood of high-grade dysplasia or invasive cancer six fold. The telomere fusion events were found to be associated with high telomerase activity (an enzyme that lengthens telomeres) and shortened telomere length.
“We have developed a simple molecular test to detect telomere fusions. This telomere fusion detection assay is a cheaper method for evaluating pancreatic cyst fluid than many next-generation sequencing approaches that are being evaluated for this purpose,” noted Dr. Goggins.
“The authors succeed in showing the presence of shortened telomeres, sporadic telomeric fusions, and increased telomerase activity in a modest proportion of pancreatic lesions,” commented Loren Joseph, MD, of the Department of Pathology at Beth Israel Deaconess Medical Center, Harvard Medical School (Boston), in an accompanying editorial. He added that the techniques used to detect fusions from cyst DNA and to measure telomere length and telomerase activity are within the scope of many molecular diagnostic laboratories.
Science Articleshttps://tinyurl.com/y9mse347
Human sperm may hold the potential to serve as biomarkers of the future health of newborn infants, according to a new study by a Wayne State University School of Medicine research team.
The study, “Sperm RNA elements as markers of health,” from the lab of Stephen Krawetz, Ph.D., the Charlotte B. Failing Professor of Fetal Therapy and Diagnosis in the WSU Department of Obstetrics and Gynecology and Center for Molecular Medicine and Genetics, indicates that RNA found in male sperm not only shows promise as a determinant in successful live birth, it may also tell us more about the health of a child as it matures.
“We explored the opportunity of using sperm RNA elements as a predictor of human health, with applications at the fertility clinic that would go hand-in-hand with the new neonatal intensive care unit genome sequencing to better health outcomes,” said Dr. Krawetz, associate director of the C.S. Mott Center for Human Growth and Development. “This leaves the intriguing possibility that, while sperm RNAs delivered to the egg inform the success of live birth, they may also open a pathway to understanding the birth and potential health of each child.
At fertilization, sperm delivers a structurally distinct genome, along with a complement of ribonucleic acids, or RNAs, and proteins to the immature egg cell. To test the hypothesis, sperm RNA elements corresponding to specific genes were characterized as a function of disease association. Dr. Krawetz’s team surveyed a total of 278,605 sperm RNA elements called short exon-sized sequences, or SREs, associated with diseases. This functional association of SREs may indicate a future phenotype, providing improved understanding of the father’s contribution to the life course of the child as well as the current state of paternal health.
In the future, if those SREs that are mutated or modified can be identified, researchers and physicians may be able to not only forecast disease or conditions, but develop ways to prevent them.
Wayne State University
www.med.wayne.edu/news/2017/12/01/sperm-rna-may-serve-as-biomarkers-of-future-health-wsu-researchers-find/
November 2025
Prins Hendrikstraat 1
5611HH Eindhoven
The Netherlands
info@clinlabint.com
PanGlobal Media is not responsible for any error or omission that might occur in the electronic display of product or company data.