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Revolutionary New Blood Test (CancerSEEK) Detects & Localizes Eight Different Cancers, Including Pancreatic; Approach Involves Liquid Biopsy and Use of Machine Learning, Legendary Bert Vogelstein Among Reporting Hopkins Scientists

Johns Hopkins Kimmel Cancer Center researchers have developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer. The test, called CancerSEEK, is a unique noninvasive, multi-analyte test that simultaneously evaluates levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood. The test is aimed at screening for eight common cancer types that account for more than 60 percent of cancer deaths in the U.S. Five of the cancers covered by the test currently have no screening test. “The use of a combination of selected biomarkers for early detection has the potential to change the way we screen for cancer, and it is based on the same rationale for using combinations of drugs to treat cancers,” says Nickolas Papadopoulos, PhD, senior author and professor of oncology and pathology. The findings were published online by Science on January 18, 2018. The article is titled “Detection and Localization of Surgically Resectable Cancers with a Multi-Analyte Blood Test” “Circulating tumor DNA mutations can be highly specific markers for cancer. To capitalize on this inherent specificity, we sought to develop a small, yet robust, panel that could detect at least one mutation in the vast majority of cancers,” says Joshua Cohen, an MD, PhD student at the Johns Hopkins University School of Medicine and the paper’s first author. “In fact, keeping the mutation panel small is essential to minimize false-positive results and keep such screening tests affordable.” The investigators initially explored several hundred genes and 40 protein markers, whittling the number down to segments of 16 genes and 8 proteins.

30-Year Study Shows Women Who Breastfeed for 6 Months or More Reduce Their Type 2 Diabetes Risk by Almost 50%

In a long-term national study, breastfeeding for six months or longer was found to cut the risk of developing type 2 diabetes nearly in half for women throughout their childbearing years, according to new Kaiser Permanente research published online on January 16, 2016 in JAMA Internal Medicine. The open-access article is titled “Lactation Duration and Progression to Diabetes in Women Across the Childbearing Years: The 30-Year CARDIA Study.” "We found a very strong association between breastfeeding duration and lower risk of developing diabetes, even after accounting for all possible confounding risk factors," said lead author Erica P. Gunderson, PhD, MS, MPH, Senior Research Scientist with the Kaiser Permanente Division of Research. Women who breastfed for six months or more across all births had a 47 percent reduction in their risk of developing type 2 diabetes compared to those who did not breastfeed at all. Women who breastfed for six months or less had a 25 percent reduction in diabetes risk. Dr. Gunderson and colleagues analyzed data during the 30 years of follow-up from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a national, multi-center investigation of cardiovascular disease risk factors that originally enrolled approximately 5,000 adults aged 18 to 30 in 1985 to 1986, including more than 1,000 members of Kaiser Permanente Northern California. The new findings add to a growing body of evidence that breastfeeding has protective effects for both mothers and their offspring, including lowering a mother's risk of breast and ovarian cancer. The CARDIA findings are also consistent with those of the NIH-funded Study of Women, Infant Feeding and Type 2 Diabetes after GDM Pregnancy (SWIFT), also led by Dr.

Hepatic Leukemia Factor (HLF) Protects Blood Stem Cells by Maintaining Them in Resting State

"The study confirms several previous studies that show the HLF gene's significance in blood formation,” says Mattias Magnusson, PhD, of Lund University, who led a new study, the results of which were published in the December 19, 2017 issue of Cell Reports. The open-access article is titled “Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool During Regeneration.” The results can have important applications in bone marrow transplants, as well as contribute to our knowledge of how leukemia develops. Maintaining blood production, especially in the case of injury, chemotherapy, or a transplantation, is dependent on a limited number of stem cells in the bone marrow. These blood stem cells have the unique capacity to make an identical copy of themselves and to mature into all the different types of blood cells. To ensure lifelong maintenance of normal blood stem cell function, most blood stem cells are held in a resting state. This protects them from exhaustion and external Impact. However, the blood stem cells can be rapidly deployed to reconstruct the blood system in the case of trauma, after which they revert to their resting state. "Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises,” explains Dr. Magnusson. Several research teams have previously identified the HLF gene as a possible stem cell regulator for both normal and carcinogenic blood formation.

Surfers & Bodyboarders Three Times More Likely to Have Antibiotic-Resistant E. coli in Their Guts Than Non-Surfers, Small Study Shows

Regular surfers and bodyboarders are three times more likely to have antibiotic-resistant E. coli in their guts than non-surfers, new research has revealed. Conducted by the University of Exeter, the “Beach Bums” study asked 300 people, half of whom regularly surf the UK's coastline, to take rectal swabs. Surfers swallow ten times more sea water than sea swimmers, and scientists wanted to find out if that made them more vulnerable to bacteria that pollute seawater, and whether those bacteria are resistant to an antibiotic. Scientists compared fecal samples from surfers and non-surfers to assess whether the surfers' guts contained E. coli bacteria that were able to grow in the presence of cefotaxime, a commonly used and clinically important antibiotic. Cefotaxime has previously been prescribed to kill off these bacteria, but some have acquired genes that enable them to survive this treatment. The study, published online on January 14, 2018 in Environment International, found that 13 of 143 (9%) of surfers were colonized by these resistant bacteria, compared to just four of 130 (3%) of non-surfers swabbed. That meant that the bacteria would continue to grow even if treated with cefotaxime. The open-access article is titled “Exposure to and Colonization by Antibiotic-Resistant E. Coli In UK Coastal Water Users: Environmental Surveillance, Exposure Assessment, and Epidemiological Study (Beach Bum Survey).” Researchers also found that regular surfers were four times as likely to harbor bacteria that contain mobile genes that make bacteria resistant to the antibiotic. This is significant because the genes can be passed between bacteria - potentially spreading the ability to resist antibiotic treatment between bacteria.

Fibromyalgia Patients Have Brain Networks Primed for Rapid Global Responses to Minor Changes (Explosive Synchronization); Similar Hypersensitivity Can Be Seen in Other Network Phenomena Across Nature and in Power Grids

New research reports that hyperreactive brain networks could play a part in the hypersensitivity of fibromyalgia. A new study finds that patients with fibromyalgia have brain networks primed for rapid, global responses to minor changes. This abnormal hypersensitivity, called explosive synchronization (ES), can be seen in other network phenomena across nature. Researchers from the University of Michigan Medical School and Pohang University of Science and Technology in South Korea report evidence of ES in the brains of people with fibromyalgia, a condition characterized by widespread, chronic pain. The open-access article, published online on January 10, 2018 in Scientific Reports, details only the second study of ES in human brain data. The article is titled “Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain.” "For the first time, this research shows that the hypersensitivity experienced by chronic pain patients may result from hypersensitive brain networks," says co-senior author Richard Harris, PhD, Associate Professor of Anesthesiology with the Chronic Pain & Fatigue Research Center (http://www.med.umich.edu/painresearch/) at the University of Michigan Medical School. "The subjects had conditions similar to other networks that undergo explosive synchronization." In ES, a small stimulus can lead to a dramatic synchronized reaction in the network, as can happen with a power grid failure (that rapidly turns things off) or a seizure (that rapidly turns things on). This phenomenon was, until recently, studied in physics rather than medicine. Researchers say it's a promising avenue to explore in the continued quest to determine how a person develops fibromyalgia.

Exosome Diagnostics Places Early-Access Shahky™ Exosome-Specific Protein Detection System at MGH Center for Systems Biology; Placement Follows Group’s Development of Prototype Assay for the Early Detection of Pancreatic Cancer

On January 9, 2018, Exosome Diagnostics, Inc. announced that it had placed an early-access version of its commercial Shahky™ System, which quantitively measures exosomal proteins, at Massachusetts General Hospital’s Center for Systems Biology in the laboratory of Dr. Hakho Lee. The Shahky System is the world’s first instrument specifically for exosomal protein analysis. Placement of this Shahky instrument, one of a number of Exosome Diagnostics early-access instruments, represents the company’s efforts within the past twelve months to develop a matured commercial system, initially created as a multiplexed nanoplasmonic research assay within the laboratory of Dr. Lee. The technology developed by Exosome Diagnostics, the Shahky System, will be used by Dr. Hyungsoon Im, an Assistant Professor of Radiology at MGH, in collaboration with Dr. Lee, to improve upon the prototype assay for the early detection of pancreatic cancer described in a May 23, 2017 Science Translational Medicine publication (http://stm.sciencemag.org/content/9/391/eaal3226) (“Multiparametric Plasma EV Profiling Facilitates Diagnosis of Pancreatic Malignancy”) by Dr. Lee, Dr. Im, and others. “In conjunction with nucleic acid detection, assessing exosomal proteins will significantly enhance diagnostic accuracy. Protein analyses can also produce actionable clinical information,” stated Dr. Lee. The commercial Shahky System has been developed and overseen by Exosome Diagnostic’s regulatory department, with design control and engineering practices that are in accordance with FDA and other applicable regulations.

Biologists Investigate Early Development of Spider Eyes to Look for Clues That May Aid Solution of Human Visual Challenges; Work May Also Speed Development of New Technologies Like Swallowable Endoscopic Cameras

With the increasing advantages of DNA sequencing, University of Cincinnati (UC) biologists are unraveling many evolutionary mysteries behind the complex world of spider vision. Looking closely at the mysterious genetic blueprint for how spider eyes developed and function is helping researchers see great opportunities for future research. New studies could include gene therapies in humans with visual problems like macular degeneration or retinal cancer. To get to these possibilities, scientists like Nathan Morehouse, PhD, UC Assistant Professor of Biology, had to look to 500 million years ago, to a time called the Cambrian Period, to put the evolution of spider eye genes into perspective. "What we found is that we go from soft-bodied ancient aquatic arthropods with no eyes, or at least eyes that don't fossilize well, to suddenly eyes that look like the eyes that we see on insects and land animals today, with basically nothing in between these stages," says Dr. Morehouse. And by "suddenly," Dr. Morehouse is talking about a small evolutionary period of 50 million years. "But for the fossil record, 50 million years is a very short time to go from no eyes to eyes like we have today," he adds. While primitive spiders and insects came onto land as two totally separate groups, they are likely to have carried with them some of the same developmental patterns for building their eyes. "We can use new genetic evidence from insects as a starting point for identifying important genes that are controlling eye development in spiders," says Dr. Morehouse. "This will excite spider biologists, and people generally interested in vision, into thinking about novel ways of building better vision. We're not quite there in terms of engineering solutions for building organic eyes yet, but hopefully that's in our future."

Western High-Fat Diet Implicated in Fatal Metastasis of Prostate Cancer; Existing Drug That Blocks Lipogenesis Prevents Metastasis in Mouse Model; New Data Is “Tremendously Actionable,” Research Leader Says

Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, the disease is invariably fatal. In a set of papers published online on January 15, 2018 in the journals Nature Genetics and Nature Communications, researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) in Boston shed new light on the genetic mechanisms that promote metastasis in the mouse model and also implicated the typical Western high-fat diet as a key environmental factor driving metastasis. The Nature Genetics article is titled An Aberrant SREBP-Dependent Lipogenic Program Promotes Metastatic Prostate Cancer.” The open-access Nature Communications article is titled “Deregulated PP1α Phosphatase Activity Towards MAPK Activation Is Antagonized by a Tumor Suppressive Failsafe Mechanism.” "Although it is widely postulated that a Western diet can promote prostate cancer progression, direct evidence supporting a strong association between dietary lipids and prostate cancer has been lacking," said first author Ming Chen, PhD, a research fellow in the laboratory of Pier Paolo Pandolfi (photo), MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. Epidemiological data links dietary fats (and obesity) to many types of cancer, and rates of cancer deaths from metastatic cancers including prostate cancer are much higher in the United States than in nations where lower fat diets are more common. While prostate cancer affects about 10 percent of men in Asian nations, that rate climbs to about 40 percent when they immigrate to the U.S., mirroring the rates among the native-born U.S. population.

Genes That Aid Spinal Cord Healing in Lamprey Also Present in Humans; Lamprey Can Fully Recover from Severed Spinal Cord; Wnt Pathway Seems Crucial

Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, and other institutions. This is consistent with the possibility that, in the long term, the same or similar genes may be harnessed to improve spinal cord injury treatment in humans. "We found a large overlap with the hub of transcription factors that are driving regeneration in the mammalian peripheral nervous system," says Jennifer Morgan, PhD, Director of the MBL's Eugene Bell Center for Regenerative Biology and Tissue Engineering, one of the authors of the study published online on January 15, 2018 in Scientific Reports. The open-access article is titled “Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery from Spinal Cord Injury in Lampreys.” Lampreys are jawless, eel-like fish that shared a common ancestor with humans about 550 million years ago. This study arose from the observation that a lamprey can fully recover from a severed spinal cord without medication or other treatment. "They can go from paralysis to full swimming behaviors in 10 to 12 weeks," says Dr. Morgan. "Scientists have known for many years that the lamprey achieves spontaneous recovery from spinal cord injury, but we have not known the molecular recipe that accompanies and supports this remarkable capacity," says Ona Bloom, PhD, of the Feinstein Institute for Medical Research and the Zucker School of Medicine at Hofstra/Northwell, a former MBL Whitman Center Fellow who collaborated on the project.

Genetic Analysis May Improve Depression Therapy

The failure of drugs such as selective serotonin reuptake inhibitors (SSRIs), used to treat depression, can be a result of genetic variations in patients. Variations within the gene that encodes the CYP2C19 enzyme results in extreme differences in the levels of escitalopram achieved in patients, according to a new study published online on January 12, 2018 in The American Journal of Psychiatry. Prescribing the dose of escitalopram (Lexapro) based on a patient's specific genetic constitution would greatly improve therapeutic outcomes. The study was conducted at Karolinska Institutet in Sweden in association with researchers at Diakonhjemmet Hospital in Oslo, Norway. The title of the article is “Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients.” Pharmaceutical treatment of depression commonly makes use of selective SSRIs, of which escitalopram is the most frequently administered clinically. However, escitalopram therapy is currently limited by the fact that some patients do not respond well to the drug, while others develop adverse reactions requiring discontinuation of treatment. In order to individualize drug therapy, researchers are attempting to establish genetic biomarkers that can predict an individual's response to drugs. In the new study, it was discovered that variation in the gene encoding the enzyme responsible for escitalopram metabolism (CYP2C19) is very important in this respect. Individuals with a variant of the gene promoting increased enzyme expression had blood levels of escitalopram too low to impact the depression symptoms, whereas patients with a defective CYP2C19 gene reached drug levels which were too high.

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