Under the banner “GeT Perfect”, Greiner Bio-One has kicked off the European promotion of the Greiner eHealth Technologies Solution – GeT. For this purpose, a modern microsite in German and English has been created. The one page site provides all essential information at a glance. GeT utilizes a flexible modular based software solution whilst applying the advantages of pre-barcoded VACUETTE tubes. The aim is to increase the efficiency of routine procedures in and around the laboratory. This page provides information on events, reference customers as well as study material. Testimonials from reference customers report on their experiences. Advantages of the system and working procedures can be seen in the form of videos and animation. All in all, the user has here a compact version of all initial information required for initiating any further steps.
www.gbo.com/get
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Thermo Fisher Scientific and HEALTH BioMed (HBM) have announced a collaboration to support HBM’s development of molecular diagnostic (MDx) kits for infectious disease and pharmacogenomics screening to serve the China market. Under the terms of a strategic agreement, HBM will submit all kits it develops on the Applied Biosystems 3500Dx Capillary Electrophoresis (CE) platform through the appropriate regulatory process with the China Food and Drug Administration (CFDA) following successful validation. “Our collaboration with Thermo Fisher Scientific will enable HBM to meet a critical need in the China market for a series of high accuracy kits designed to run on a single CE platform to improve human health outcomes,” said Jianwei Yu, Chairman and CEO of HEALTH BioMed. “Molecular diagnostics such as these can improve diagnosis and treatment strategies in hospital settings while also helping to decrease antibiotic abuse.” HBM intends to leverage its CE-based Advanced Fragment Analysis (AFA) technology and reagents, which are currently CE-IVD-and cFDA-marked as is the ABI 3500Dx platform, to develop multiple assays under its SureX brand of multiplex kits. HBM’s current offering for human papillomavirus (HPV) screening, for example, is designed to target 25 high- and low-risk markers with high sensitivity, specificity and low hands-on-time. Development of its pharmacogenomics kits under the agreement will be designed to further support precision medicine initiatives in the country. “As a world leader in serving science, we are proud to be an enabling partner to help HEALTH BioMed build its portfolio of molecular diagnostics designed to better manage human health in China,” said Mark Smedley, president of genetic sciences at Thermo Fisher. “We are committed to working with diagnostic partners around the world who share our vision to drive the era of precision medicine.”
www.thermofisher.com www.nb-health.com/HGT
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Prostate cancer patients have been offered hope after scientists at Newcastle University have identified a new group of molecules that could be targeted to slow tumour growth.
Our findings are very significant for future treatments as they identify a new group of molecules in prostate cancer which could be targeted therapeutically.
Experts used an advanced screening technique which found hundreds of genes were affected by the male hormone testosterone. It is believed this could lead to new diagnostic tests and treatments.
Among the 700 genes identified was an important set that add sugar groups – known as glycans – to the surface of prostate cancer cells. This group has never been investigated before.
Treatments targeting glycan sugar groups have been developed for other types of the illness, such as breast cancer. It is hoped these treatments could also be used for prostate cancer.
Results of the research suggest that testosterone changes glycans to make cancer cells more likely to survive, grow and spread to other parts of the body.
Scientists say there is the potential to target these glycans which could stop the growth and spread of tumours and save lives.
Dr Jennifer Munkley, Research Associate at the Institute of Genetic Medicine, Newcastle University, co-led the three-year research project with Professor David Elliott.
She said: “Our findings are very significant for future treatments as they identify a new group of molecules in prostate cancer which could be targeted therapeutically.
“Now we have identified these glycans we will be able to develop strategies to inhibit them and help patients with this condition.
Glycans have the potential to be used as part of a diagnostic test to help doctors decide which prostate cancers need treatment.
One in eight men will be diagnosed with the condition. It is the most common cancer in UK males, and there is a need to identify how the disease progresses and for treatment options to be established.
Researchers at Newcastle University used a technique, called RNA-sequencing, to identify the new set of genes that are important.
The genes identified may provide novel ways the disease can be monitored in patients to predict the most aggressive prostate cancers that need to be treated.
Simon Grieveson, Head of Research Funding at Prostate Cancer UK, said: “There’s a desperate need for more treatments for men with advanced prostate cancer, who currently have too few options available to them.
“However, in order to develop new, effective treatments, we need to understand more about the genetic makeup of aggressive prostate cancers and identify what makes them tick.
“This promising research has unearthed a new group of genes which could play a part in cancer cell survival and development, and could pave the way for new treatments in the future.
Newcastle University
www.ncl.ac.uk/press/news/2016/07/prostatecancerstudy/
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Genomic makeup of colorectal cancers predicts immune system ability to fight tumours
Colorectal cancers heavily bedecked with tumour-related proteins called neoantigens are likely to be permeated with disease-fighting white blood cells, researchers at Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard report in a new study. Because such an influx of white blood cells often signifies an immune system attack on cancer, the discovery will sharpen research into therapies that make tumours more vulnerable to such an attack.
The discovery was made by combining several data sets from patients in two large health-tracking studies, the Nurses’ Health Study and the Health Professionals Follow-up Study. Researchers first performed whole-exome sequencing on colorectal tumour samples from 619. This information was merged with data from tests of the immune system’s response to the tumours and with patient clinical data, including length of survival.
“We were looking for genetic features that predict how extensively a tumour is infiltrated by lymphocytes [certain white blood cells] and which types of lymphocytes are present,” said study co-lead author, Marios Giannakis, MD, PhD, medical oncologist and clinical investigator at the Dana-Farber Gastrointestinal Cancer Treatment Center, and researcher at the Broad Institute of MIT and Harvard. “We found that tumours with a high ‘neoantigen load’ – which carry large quantities of neoantigens – tended to be infiltrated by a large number of lymphocytes, including memory T cells, which provide protection against previously encountered infections and diseases. Patients whose tumours had high numbers of neoantigens also survived longer than those with lower neoantigen loads.”
Neoantigens are deviant forms of protein antigens, which are found on normal cells. Genetic mutations often cause cancer cells to produce abnormal proteins, some of which get lifted to the cell surface, where they serve as a red flag to the immune system that something is amiss with the cell.
“There can be hundreds or thousands of neoantigens on tumour cells,” Giannakis explained. “Only a few of these may actually provoke T cells to infiltrate a tumour. But the more neoantigens on display, the greater the chance that some of them will spark an immune system response.”
Therapies known as immune checkpoint inhibitors work by removing some of the barriers to an immune system attack on cancer. Although these agents have produced astonishing results in some cases, they’re generally effective only in patients whose immune system has already launched an immune response to cancer. By showing that tumours with high antigen loads are apt to be laced with T cells – and therefore to have provoked an immune response – the study may help investigators identify which patients are most likely to benefit in new clinical trials of immune checkpoint inhibitors.
The study’s genomic analysis of colorectal tumour samples also found several often-mutated genes that had not previously been strongly associated with the disease, including BCL9L, RBM10, CTCF, and KLF5. The discovery of their prevalence in colorectal cancer suggests that they may be valuable targets for new therapies.
Dana-Farber Cancer Institute
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Most melanomas are driven by mutations that spur out-of-control cell replication, while nevi (moles composed of non-cancerous cells at the skin surface) harbouring the same mutations do not grow wildly. However, changes in the level of gene expression can cause nevi to become melanomas.
Dermatologists surmise that 30 to 40 percent of melanomas (approximately 30,000 cases per year) may arise in association with a nevus. However, clinicians would like to be able to better distinguish between the two, especially in borderline cases when they examine skin tissue after a patient biopsy.
Senior author John T. Seykora, MD, PhD, a professor of Dermatology in the Perelman School of Medicine at the University of Pennsylvania, led a study that found that decreased levels of the gene p15 represents a way to determine if a nevus is transitioning to a melanoma. The protein p15 functions to inhibit nevus cell proliferation.
“We showed that p15 expression is a robust biomarker for distinguishing nevus from melanoma,” said Seykora. “Making this distinction has been a long-standing issue for dermatologists. We hope that this new finding will help doctors determine if a nevus has transformed to melanoma. This could help doctors and patients in difficult cases. Current research will hopefully move this into the realm of standard practice in about one to two years.”
Decreased expression in the related protein p16 has also been associated with melanoma, but p15 appears to be a primary driver of oncogene-induced cell senescence in nevus cells. When p15 levels drop, then nevus cells begin to grow.
The team stained human nevus and melanoma tissue samples with p15 and p16 antibodies. Staining was evaluated and graded for percentage and intensity to determine an “H score,” which correlates with the level of protein in the cells. This approach could also form the basis of a clinical determination, taking the form of an antibody test for p15 from a patient’s biopsy specimen. “If the staining level is high then that would be most consistent with a benign nevus,” Seykora said. “If the staining level is low then that would be consistent with a melanoma.”
RNA was also extracted from 14 nevus and melanoma tissue samples to determine levels of p15 mRNA. The expression of p15 mRNA was significantly increased in melanocytic nevi compared with melanomas as determined by real-time quantitative RT-PCR analysis.
Penn Medicine
www.uphs.upenn.edu/news/News_Releases/2016/11/seykora/
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A new device for studying tumour cells can trap 10,000 individual cells in a single chip.
The technique, developed at the University of Michigan, could one day help screen potential cancer treatments based on an individual patient’s tumour and help researchers better understand so-called cancer stem cells. It also sheds light on a controversy: are large cells or small cells more likely to be cancer stem cells?
Cancer cells are not all the same, and one theory holds that no more than 5 percent of the cells in a tumour are cancer stem cells. These few may be the only cells capable of causing a relapse or metastasis.
‘Most normal cells will die if they are not anchored to something, but cancer stem cells can survive. They can become circulating tumour cells and come to another area of the body,’ said Euisik Yoon, professor of electrical engineering and computer science, and biomedical engineering.
The team led by Yoon designed and made a device that takes advantage of this ability in hopes of understanding cancer stem cells better: how to identify them, what causes them to grow or die, and how to target them with cancer treatments. Their chip contains up to 12,800 wells for catching individual cancer cells. The team tested the chip with breast cancer cells, donated by researchers in the U-M Comprehensive Cancer Center.
They mixed the cells into a solution and ran the liquid through tiny channels in a plastic chip. Each channel was lined with chambers for trapping single cells.
The chambers have small openings to a parallel channel, which creates a draft that draws cells in — sort of like the drain in a sink. Once a cell is trapped, it blocks that opening and stops the draft. This ensures that, most of the time, only one cell is pulled into each chamber.
The walls of the chamber are coated so that the cell can’t latch on. As a result, normal cells that can’t cause metastases die over the course of a few days, leaving behind just the cancer stem cells. These cells reproduce in their chambers, forming tiny floating colonies, or tumorspheres.
While the ability to isolate 10,000 individual cells is impressive, it wouldn’t be useful if the team had to manually record every one, as required by most devices that capture cancer cells. The key is their computer algorithm, capable of combing through the microscope images and assessing the size and number of cells in each well. The algorithm’s particular talent is identifying cells no matter whether they show up dimly or brightly in the microscope image.
‘Our method is special because we really want to enable the study of many cells at once,’ said Yu-Heng Cheng, a doctoral student in electrical engineering and computer science. ‘Cancer cells have many different appearances, and our algorithm recognizes them.’
University of Michigan
www.mcancer.org/news/archive/cancer-stem-cells-new-method-analyzes-10000-cells-once
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Distribution of single nucleotide variant (SNV) counts detected through exome sequencing of melanoma samples, grouped by the presence of R alleles of the MC1R locus shown as a boxplot with median, quartiles, whiskers and outliers.
For the first time, researchers at the Wellcome Trust Sanger Institute and University of Leeds have proved that gene variants associated with red hair, pale skin and freckles are linked to a higher number of genetic mutations in skin cancers. The burden of mutations associated with these variants is comparable to an extra 21 years of sun exposure in people without this variant.
The research showed that even a single copy of a red hair-associated MC1R gene variant increased the number of mutations in melanoma skin cancer; the most serious form of skin cancer. Many non-red haired people carry these common variants and the study shows that everyone needs to be careful about sun exposure.
Red-headed people make up between one and two percent of the world’s population but about 6 per cent of the UK population. They have two copies of a variant of the MC1R gene which affects the type of melanin pigment they produce, leading to red hair, freckles, pale skin and a strong tendency to burn in the sun.
“It has been known for a while that a person with red hair has an increased likelihood of developing skin cancer, but this is the first time that the gene has been proven to be associated with skin cancers with more mutations.’
‘Unexpectedly, we also showed that people with only a single copy of the gene variant still have a much higher number of tumour mutations than the rest of the population. This is one of the first examples of a common genetic profile having a large impact on a cancer genome and could help better identify people at higher risk of developing skin cancer.”
Dr David Adams, joint lead researcher at the Wellcome Trust Sanger Institute
The researchers analysed publically available data-sets of tumour DNA sequences collected from more than 400 people. They found an average of 42 per cent more sun-associated mutations in tumours from people carrying the gene variant.
“This is the first study to look at how the inherited MC1R gene affects the number of spontaneous mutations in skin cancers and has significant implications for understanding how skin cancers form. It has only been possible due to the large-scale data available. The tumours were sequenced in the USA, from patients all over the world and the data was made freely accessible to all researchers. This study illustrates how important international collaboration and free public access to data-sets is to research.”
Exposure to ultraviolet light from either sunlight or sunbeds causes damage to DNA and it has been thought that the type of skin pigment associated with red-heads could allow more UV to reach the DNA. While this may be one mechanism of damage, the study also revealed that the MC1R gene variation not only increased the number of spontaneous mutations caused by ultraviolet light, but also raised the level of other mutations in the tumours. This suggests that biological processes exist in cancer development in people with MC1R variation that are not solely related to ultraviolet light.
“This important research explains why red-haired people have to be so careful about covering up in strong sun. It also underlines that it isn’t just people with red hair who need to protect themselves from too much sun. People who tend to burn rather than tan, or who have fair skin, hair or eyes, or who have freckles or moles are also at higher risk.’
Sanger Institute
www.sanger.ac.uk/news/view/red-hair-gene-variant-drives-skin-cancer-mutations
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Researchers from Massachusetts Eye and Ear and Schepens Eye Research Institute have shown an association between a defective myogenic response — the regulatory increase or decrease in blood pressure to keep blood flow within the vessels of the retina constant — and early, accelerated development of retinopathy in patients with type 1 diabetes. These findings identify one mechanism to explain why some patients develop diabetic retinopathy sooner than others. Furthermore, the findings provide a target for future study, which may lead to therapies to delay or prevent the development of accelerated onset diabetic retinopathy.
“In patients with a normal myogenic response, the retinal vessels constrict when increased pressure arrives, to maintain constant blood flow and avoid damage to the smaller vessels in the retina,” said Mara Lorenzi, M.D., senior scientist at Massachusetts Eye and Ear/Schepens Eye Research Institute and a professor of ophthalmology, part-time at Harvard Medical School. “But we saw that, in about half of the diabetic patients in our study, the vessels did not constrict. In fact, paradoxically, some patients’ vessels dilated, and the blood flow to the retina was increased. This becomes a mechanism of damage for the small vessels, because these tiny, delicate capillaries are exposed to a big flow of pressure that can lead to the little haemorrhages and fluid leakage that are characteristic of diabetic retinopathy.”
The study included a small prospective study, in which the researchers closely followed 17 patients with type 1 diabetes whose myogenic responses had been measured four years prior. In approximately half of those patients, the researchers had observed defective myogenic responses. Five out of seven patients with defective myogenic responses developed accelerated diabetic retinopathy. The study also included a different group of patients with type 1 diabetes who had just developed retinopathy. Among these patients, the defective myogenic response was found only in those in whom retinopathy had appeared after a short duration of diabetes (fewer than 15 years of diabetes).
The most common diabetic eye disease and a leading cause of blindness in American adults, diabetic retinopathy occurs when blood vessels in the retina become damaged and leak fluid. Accumulation of fluid into the retina can lead to macular oedema . As the damage due to diabetes progresses, the vessels become occluded and can no longer carry blood. New blood vessels grow on the surface of the retina (proliferative retinopathy); but the new vessels are immature and may rupture impairing vision. Loss of visual acuity as a result of diabetic retinopathy is often the first warning sign for patients yet to be diagnosed with type 2 diabetes.
Currently, there are no treatments for diabetic retinopathy beyond controlling blood sugar and blood pressure levels. The new vessels of proliferative retinopathy can be treated with laser techniques, often at the expense of a portion of the retina. With the knowledge gained from the new studies, the researchers hope to target the defective myogenic response and develop therapies to prevent the development of accelerated diabetic retinopathy in this population. A larger study is needed to test the predictive capability of this abnormality.
Massachusetts Eye and Ear
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The latest developments in prenatal technology conceived by scientists at the Wayne State University School of Medicine that make it possible to test for genetic disorders a little more than one month into pregnancy were revealed. In the article, the WSU researchers wrote that their non-invasive testing method – Trophoblast Retrieval and Isolation from the Cervix (TRIC) – offers the accuracy of more invasive tests, such as the needle-directed amniocentesis, and can also be utilized five to 10 weeks earlier than current testing modalities. TRIC was first publicized in 2014 in studies led by principal investigator and Professor of Obstetrics and Gynecology D. Randall Armant, Ph.D. The method isolates several hundred foetal cells that migrate from the placenta into the uterus using a retrieval technique akin to the common Pap smear, and can be done as early as five weeks into pregnancy. Armant’s co-principal investigator in the latest research is Associate Professor of Obstetrics and Gynecology Sascha Drewlo, Ph.D., who joined the team in 2014 to provide expertise in molecular biology and perinatal medicine.
A related paper published by the two “Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease,” describes the correlation between the levels of certain proteins in the foetal cells isolated by TRIC during the first trimester and the development of intrauterine growth restriction, which results in a small, undernourished foetus in the womb, or preeclampsia – hypertension and kidney disorder of the mother – in the last trimester.
“This finding suggests that it might one day be possible to test these protein levels to identify pregnancies at risk for complications. Such a test could help physicians to better manage the health of mother and baby, and would streamline research on new interventions to prevent or limit the effects of disease,” Armant said.
The paper demonstrates the researchers’ ability to isolate foetal DNA from the cells obtained by TRIC. Since the placenta is derived from the embryo and its DNA is the same as that of the foetus, the researchers can use cells obtained by TRIC for prenatal genetic testing. The paper was co-first authored by Chandni Jain, Ph.D., and Leena Kadam, working in the laboratories of Armant and Drewlo. “We sequenced the foetal DNA and compared it to that of the mothers, proving that they were different, but the foetal DNA always contained one copy of the mother’s DNA genes. We also had some DNA from the placenta and found that it was identical to the foetal DNA,” Armant said.
The sequencing was completed in 20 consecutive pregnancies collected at five to 19 weeks, with minimal maternal DNA contamination.
Wayne State Universityresearch.wayne.edu/news/studies-reveal-wsu-conceived-non-invasive-prenatal-genetic-test-is-accurate-five-weeks-into-pregnancy-21140
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An international research team has linked rare variations in a cell membrane protein to the wide variation in symptom severity that is a hallmark of porphyria, a rare disorder that often affects the skin, liver and nervous system. St. Jude Children’s Research Hospital helped to lead the research.
Porphyrias are a family of diseases usually caused by inherited mutations in one of the eight enzymes involved in assembling heme. Heme is a molecule that plays a critical role in oxygen transport, drug metabolism and other vital physiological processes.
In this study, researchers discovered rare variations in the ABCB6 gene, also called Lan. The variations were associated with the toxic build-up in cells of chemicals produced during heme assembly. Investigators reported that the variants were more common in patients with severe porphyria than in those with less severe symptoms.
“One of the mysteries of this disease has been why some individuals with the same genetic defect have mild symptoms while others have severe symptoms and require hospitalization in the intensive care unit,” said corresponding author John Schuetz, Ph.D., a member of the St. Jude Department of Pharmaceutical Sciences. “Using gene sequencing, biochemical analysis and a new mouse model of the disease, we have identified variations in ABCB6 as an unexpected genetic modifier of porphyria severity.”
The discovery followed DNA sequencing of the protein-coding regions, or exomes, of seven porphyria patients with a history of life-threatening symptoms and hospitalization in the intensive care unit. They were among the 36 porphyria patients treated at the Royal Prince Alfred Hospital in Sydney, Australia, included in the study.
Researchers found that five of the seven patients carried rare versions of ABCB6 and made little or no functional ABCB6 protein. Sixty-two percent of patients with the rare ABCB6 variants were admitted to the intensive care unit compared to about 7 percent of other patients.
ABCB6 is carried on the surface of red blood cells, where 85 percent of heme is produced. The protein is one of several proteins that export porphyrins and related molecules from liver, blood and other cells.
Jann Ingmire
St. Jude Children’s Research Hospital
www.stjude.org/media-resources/news-releases/2016-medicine-science-news/rare-genetic-variations-may-solve-mystery-of-porphyria-severity-in-some-patients.html
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