#Researchers discover cancer markers may be visible early during human development Researchers at the Virginia Bioinformatics Institute have uncovered a link between the genomes of cells originating in the neural crest
and development of tumors a discovery that could lead to new ways to diagnose and treat cancer.
The new finding, recently published in Oncotarget, resolves why some cancer types share genomic and clinical features.
The discovery may also lead to new ways to diagnose and treat brain cancer, such as gliomas, medulloblastomas, and neuroblastomas;
and skin cancer, known as melanoma. More than 22,000 new cases of brain cancer and more than 73,000 new cases of skin cancer and were expected to arise in Americans in 2015, according to the National Cancer Institute.
To reveal when cancer-causing genomic changes occur, a research group led by Harold kipgarner, a professor in the departments of biological science, computer science,
and basic science at Virginia Tech Carilion Medical school, analyzed an often ignored part of the human genome repetitive DNA sequences referred to as microsatellites.
More than 1 million microsatellites exist in the human genome including in neural crest tissues, a thin layer of cells within an embryo that contains genetic instructions to build hundreds of cell types, from neurons to adrenal cells.
Neurological tumors, for example, may arise from glial cells that develop from the crest. Researchers with the institute Medical Informatics Systems division say cancer types can be found
or predicted from specific markers within these repetitive sequences, known as cancer-associated microsatellite loci, or CAML.
Long considered unk DNAOR ark matterwithin the genome because their function was unclear microsatellites are known for their role in certain diseases such as Fragile X and Huntington disease.
Garner group has shown that these regions can be informative about diseases ranging from cancer to autism spectrum disorder.
With more study, researchers believe interrelated hereditary and genetic traits of certain cancers can be traced to their common origin at the neural crest,
leading to potentially better therapies and easier tumor identification. The findings have been licensed to Genomeon, a company co-founded by Garner to develop new ways to assess cancer risk,
create diagnostics, and explore potential drug targets to help cancer patients p
#How chronic inflammation can lead to cancer Chronic inflammation caused by disease or exposure to dangerous chemicals has long been linked to cancer,
but exactly how this process takes place has remained unclear. Now, a precise mechanism by which chronic inflammation can lead to cancer has been uncovered by researchers at MIT a development that could lead to improved targets for preventing future tumors.
In a paper published in the Proceedings of the National Academy of Sciences, the researchers unveil how one of a battery of chemical warfare agents used by the immune system to fight off infection can itself create DNA mutations that lead to cancer.
As many as one in five cancers are believed to be caused or promoted by inflammation. These include mesothelioma,
a type of lung cancer caused by inflammation following chronic exposure to asbestos, and colon cancer in people with a history of inflammatory bowel disease, says Bogdan Fedeles,
a research associate in the Department of Biological engineering at MIT, and the paper lead author.
Innate immune response Inflammation is part of the body innate response to invading pathogens or potentially harmful irritants.
The immune system attacks the invader with a number of reactive molecules designed to neutralize it,
including hydrogen peroxide, nitric oxide and hypochlorous acid. However, these molecules can also cause collateral damage to healthy tissue around the infection site:
he presence of a foreign pathogen activates the immune response, which tries to fight off the bacteria,
but in this process it also damages some of the normal cells, Fedeles explains. Previous work by Peter Dedon, Steven Tannenbaum, Gerald Wogan,
and James Fox all professors of biological engineering at MIT had identified the presence of a lesion,
or site of damage in the structure of DNA, called 5-chlorocytosine (5clc) in the inflamed tissues of mice infected with the pathogen Helicobacter hepaticus.
This lesion, a damaged form of the normal DNA base cytosine, is caused by the reactive molecule hypochlorous acid the main ingredient in household bleach
which is generated by the immune system. The lesion 5clc, was present in remarkably high levels within the tissue,
says John Essigmann, the William R. 1956) and Betsy P. Leitch Professor in Residence Professor of Chemistry, Toxicology and Biological engineering at MIT,
who led the current research. hey found the lesions were very persistent in DNA, meaning we don have a repair system to take them out,
Essigmann says. n our field lesions that are persistent, if they are also mutagenic, are the kind of lesions that would initiate cancer,
he adds. DNA sequencing of a developing gastrointestinal tumor revealed two types of mutation: cytosine (C) bases changing to thymine (T) bases,
and adenine (A) bases changing to guanine (G) bases. Since 5clc had not yet been studied as a potentially carcinogenic mutagen,
the researchers decided to investigate the lesion further, in a bid to uncover if it is indeed mutagenic.
Using a technique previously developed in Essigmann laboratory, the researchers first placed the 5clc lesion at a specific site within the genome of a bacterial virus. They then replicated the virus within the cell.
The researchers found that, rather than always pairing with a guanine base as a cytosine would,
the 5clc instead paired with an adenine base around 5 percent of the time a medically relevant mutation frequency, according to Essigmann.
when triggered by infection, fires hypochlorous acid at the site, damaging cytosines in the DNA of the surrounding healthy tissue.
he explains. his scenario would best explain the work of James Fox and his MIT colleagues on gastrointestinal cancer.
the researchers replicated the genome containing the lesion with a variety of different types of polymerase,
or patterns of DNA mutations, associated with cancerous tumors. e believe that in the context of inflammation-induced damage of DNA,
says the paper provides a novel mechanistic link between chronic inflammation and cancer development. ith a combination of biochemical,
a type of mutation that is frequently observed in human cancers, Wang says. Studies of tissue samples of patients suffering from inflammatory bowel disease have found significant levels of 5clc,
Fedeles adds. By comparing these levels with his team findings on how mutagenic 5clc is,
the researchers predict that accumulation of the lesions would increase the mutation rate of a cell up to 30-fold,
who was honored with the prestigious Benjamin F. Trump award at the 2015 Aspen Cancer Conference for the research r
and hence is a promising step forward for the repair of peripheral nerve injuries. This research has just been published in the scientific journal Development at http://dev. biologists. org/Currently,
Motoharu Sakaue together with Maya Sieber-Blum, Professor of Stem Cell Sciences at the Institute of Genetic Medicine in Newcastle, investigated the possibility of making Schwann cells,
showing that they could interact with nerves in vitro. he next step is to determine, for example in animal models of peripheral nerve injury,
This study identifies a biologically relevant and accessible source of cells that could be used for generating sufficient quantities of Schwann cells and thus offers great potential in the repair of peripheral nerve injuries r
#Important regulation of cell invaginations discovered Lack of microinvaginations in the cell membrane, caveolae, can cause serious diseases such as lipodystrophy and muscular dystrophy.
resulting in diseases. Having too few invaginations is associated with atrial fibrillation. A total absence of invaginations causes lipodystrophy and muscular dystrophy combined with fatal cardiac arrhythmia. he latter is an unpleasant disease
CGL4, which usually leads to death in the patient teenage years. Many children presumably also die from this disease during their first week of life,
without any diagnosis other than udden infant death syndrome'says Karl Swärd and Catarina Rippe, researchers at Lund University.
About ten different genes contribute to the formation of caveolae. Until recently it was known not how these genes are coordinated.
and provides insight into how to combat diseases caused by a lack of caveolae. Moreover, the discovery paves the way for further studies on the significance of caveolae for cancer
and renal diseases. hese transcription factors regulate the cellsability to move and therefore play an important role in metastasis,
for example says Karl Swärd who, together with colleagues at Lund University, is also investigating whether the regulatory mechanism is activated in the case of kidney disease h
#Could flu someday be prevented without a vaccine? Researchers have discovered a way to trigger a preventive response to a flu infection without any help from the usual players the virus itself or interferon, a powerful infection fighter.
The finding, in both mouse and human cells, suggests that manipulating a natural process could someday be an alternative way to not just reduce the severity of the flu,
but prevent infection altogether. he flu vaccine needs to change every year because the virus is constantly mutating.
said Jacob Yount, assistant professor of microbial infection and immunity at The Ohio State university and senior author of the study.
but the scientistslong-term goal is to develop a vaccine-independent method to prevent flu infections. f we were to have an outbreak of some pandemic influenza virus similar to
I could envision using this technique to help people who are particularly vulnerable to infection,
he said. t would work best if used before an infection, because the strategy prevents cells from becoming infected in the first place.
The research is published in the journal PLOS Pathogens. The method involves raising the level of a protein that is known to be effective against all strains of influenza ever tested.
The trick for infection prevention, however, is boosting that protein level in cells before the virus shows up.
Doing that, the scientists discovered in this study, involves suppressing the function of another protein. The protein effective against influenza is called IFITM3 (
pronounced I-fit-M-3, for interferon-induced transmembrane protein 3). Under natural conditions, IFITM3 is produced in large quantities only after the flu virus is present,
so it can reduce the severity of infection. But the way it targets the virus by trapping it
and disabling its ability to make copies of itself means that increasing the protein level before the flu ever arrives would prevent infection from occurring.
and fend off an influenza attack. This enzyme, also a protein, proved to be the silver bullet in Yount work on flu prevention.
and greater resistance to infection by flu viruses. IFITM3 is known to be important to humans
because previous research has shown that it is identified the only protein containing a frequent genetic mutation linked to severe flu infections.
because mice lacking the same IFITM3 protein are highly susceptible to flu infections. Being able to stimulate this response is important for many reasons, not the least
Interferon infection-fighting power is accompanied by severe side effects most commonly associated with its former use as a treatment for Hepatitis C that include, not surprisingly,
Yount said. hat was a huge finding that you don need an infection or interferon to increase the level of IFITM3.
But later in life, lacking NEDD4 might not pose any health problems which is why Yount is currently testing the effects of suppressing NEDD4 on adult mice
#Engineering a permanent solution to genetic diseases In his mind, Basil Hubbard can already picture a new world of therapeutic treatments for millions of patients just over the horizon.
It a future in which diseases like muscular dystrophy, cystic fibrosis and many others are treated permanently through the science of genome engineering.
replacing the damaged genetic code with healthy DNA. here is a trend in the scientific community to develop therapeutics in a more rational fashion,
says Hubbard, an assistant professor of pharmacology in the University of Alberta Faculty of medicine & Dentistry. ee moving towards a very logical type of treatment for genetic diseases,
our disease is caused by a mutation in gene X, and wee going to correct this mutation to treat it.?
In theory, genome engineering will eventually allow us to permanently cure genetic diseases by editing the specific faulty genes. evolutionizing health caregenome engineering involves the targeted, specific modification of an organism genetic information.
and may one day revolutionize medical care. One of the obstacles still to be addressed in the field before it can see widespread use in humans is how to ensure the proteins only affect the specific target genes in need of repair.
but more improvements are needed to ensure off-target genes aren modified result that could potentially cause serious health problems itself.
Examples include diseases such as hemophilia sickle-cell anemia, muscular dystrophy and cystic fibrosis. Though the field is still in its relative infancy,
Hubbard says human clinical trials involving sequence-specific DNA-editing agents are already underway. If successful, he expects the first clinical applications could be seen in the next decade.
gene editing could possibly provide a permanent cure for a lot of different diseases, says Hubbard. e still have to overcome many hurdles,
but I think this technology definitely has the potential to be transformative in medicine. h
which can accurately detect malignant melanoma without a biopsy. The report, published online in Nature Scientific Reports yesterday (August 11),
55 patients with atypical moles agreed to have monitored their skin by researchers at Pisa University Hospital using a laser Doppler system.
which means that melanoma is identified in all cases where it is ruled present, and out in 90.9%of cases where it is not. rofessor Marco Rossi of Pisa University said:
kin malignant melanoma is a particularly aggressive cancer associated with quick blood vessel growth which means early diagnosis is vital for a good prognosis.
The current diagnostic tools of examination by doctors followed by biopsy inevitably leads to many unnecessary invasive excisions. his simple, accurate,
in vivo distinction between malignant melanoma and atypical moles may lead to a substantial reduction in the number of biopsies currently undertaken. ource:
Lancaster Universit L
#Nicotine-eating bacteria could one day help smokers kick the habit Most people who smoke cigarettes know it bad for their health,
Tobacco use remains the leading cause of preventable disease, disability and death in the U s. Smokers who want to quit can turn to various pharmacological aids.
These include patches gum and other nicotine-releasing products designed to replace cigarettes, as well as drugs that sequester nicotine in the body to prevent it from reaching the brain,
of which took less than five days to convert sugar into one of two medicinal compounds: either thebaine,
this could broaden access to many plant-based medicines. For thousands of years, people have used yeast to ferment wine,
Now researchers at Stanford have engineered genetically yeast to make painkilling medicines, a breakthrough that heralds a faster and potentially less expensive way to produce many different types of plant-based medicines.
Writing today in Science, the Stanford engineers describe how they reprogrammed the genetic machinery of baker yeast
It can take more than a year to produce a batch of medicine, starting from the farms in Australia,
and refined into medicines. hen we started work a decade ago, many experts thought it would be impossible to engineer yeast to replace the entire farm-to-factory process,
400 gallons of bioengineered yeast to produce a single dose of pain relief the experiment proves that bioengineered yeast can make complex plant-based medicines. his is only the beginning,
and demonstrate for opioid pain relievers can be adapted to produce many plant-derived compounds to fight cancers,
infectious diseases and chronic conditions such as high blood pressure and arthritis. rom plant to test tubesmany medicines are derived from plants,
to reprogram the cells into custom chemical assembly lines to produce medicinal compounds. An important predecessor to the Stanford work has been the use of genetically engineered yeast to produce the antimalarial drug artemisinin.
the Stanford team had to fill in a missing link in the basic science of plant-based medicines.
Many plants, including opium poppies, produce (S)- reticuline, a molecule that is a precursor to active ingredients with medicinal properties.
Smolke said. e need options to help ensure that the bio-based production of medicinal compounds is developed in the most responsible way. molke said that in the United states,
where opioid medicines are already widely available, the focus is on potential misuse. But the World health organization estimates that 5. 5 billion people have little
and the techniques we developed show that it is possible to make important medicines from scratch using only yeast,
and fairly provide medicines to all who need
#Scientists pioneer method to track water flowing through glaciers Researchers for the first time have used seismic sensors to track meltwater flowing through glaciers and into the ocean,
#Study shifts understanding of how bone fractures heal It time to rewrite the textbook description of bone fracture healing.
a protein that was thought to play a key role in fracture healing, is required not. Instead, the breakdown of fibrin is essential for fracture repair.
The findings, reported in the August issue of the Journal of Clinical Investigation, shift understanding of how fractures heal
and have implications for efforts to promote fracture repair. any of the current pharmaceutical protocols are based on using fibrin to promote fracture healing,
said Jonathan Schoenecker, M d.,Ph d, . assistant professor of Orthopaedic Surgery and Rehabilitation. n certain instances it may help,
but wee shown for sure that you don need it. Bone biology does not require fibrin to heal a fracture.
Fibrin is involved in blood clotting; it forms a meshlike net that traps platelets to form a clot.
Schoenecker said. hen you have a fracture, you have a huge disruption of that vascularity.
Since fibrin is the main protein at the site of a fracture, it was thought to promote repair by providing a scaffold for the initial phase of new bone formation.
however, that fracture repair was normal in mice missing the fibrin precursor fibrinogen. The investigators had reported previously the importance of vascular re-connection for bone fracture healing.
Using imaging techniques they developed to simultaneously study angiogenesis (new blood vessel growth) and bone formation after fracture,
they found that blood vessels grow first at the ends of the fracture, extend and reconnect. Then new bone forms. herefore, any condition associated with vascular disease
and thrombosis will impair fracture healing, Schoenecker said. It follows that if fibrin is removed not efficiently,
it gets in the way, he said. In the new studies, the team demonstrated that mice missing the factor that clears fibrin had impaired vascularization and bone union.
Genetic manipulations to deplete fibrinogen in these mice restored normal fracture repair. ibrin puts a cog in the machine
and you don get the anastomosis (vessel reconnection), Schoenecker said. The findings may explain why obesity, diabetes,
smoking and advanced age impair fracture repair. They are associated all with impaired fibrin clearance, he explained.
and orthopaedic surgery. t was unexpected totally that fibrin clearance is essential to prevent heterotopic ossification,
and plates used in orthopaedic surgeries, so that those devices don disrupt the ability of blood vessels to grow
as such big injuries of an incredibly vascular structure inevitably require a clot in order not to bleed to death,
He points out that some of the medications developed for cardiovascular medicine to prevent clotting may find new purposes in enhancing tissue repair and regeneration i
#Newly discovered cells regenerate liver tissue without forming tumors Hybrid hepatocytes proliferate and replenish liver mass after chronic liver injuries in micehybrid hepatocytes proliferate
and replenish liver mass after chronic liver injuries in micethe mechanisms that allow the liver to repair
and regenerate itself have long been a matter of debate. Now researchers at University of California, San diego School of medicine have discovered a population of liver cells that are better at regenerating liver tissue than ordinary liver cells, or hepatocytes.
and show that they are able to regenerate liver tissue without giving rise to cancer.
Of all major organs, the liver has the highest capacity to regenerate that why many liver diseases,
including cirrhosis and hepatitis, can often be cured by transplanting a piece of liver from a healthy donor.
In this latest study, led by Michael Karin, Phd, Distinguished Professor of Pharmacology and Pathology, researchers traced the cells responsible for replenishing hepatocytes following chronic liver injury induced by exposure to carbon tetrachloride, a common environmental toxin.
That when they found a unique population of hepatocytes located in one specific area of the liver,
and replenish liver mass after chronic liver injuries. Since the cells are similar to normal hepatocytes
when their therapeutic job is done. As a result ipscs carry a high risk of giving rise to tumors.
To test the safety of hybrid hepatocytes, Karin team examined three different mouse models of liver cancer.
They found no signs of hybrid hepatocytes in any of the tumors, leading the researchers to conclude that these cells don contribute to liver cancer caused by obesity-induced hepatitis
or chemical carcinogens. ybrid hepatocytes represent not only the most effective way to repair a diseased liver,
but also the safest way to prevent fatal liver failure by cell transplantation, Karin said p
Two recent studies pointed to possible flaws in the methods used to identify irisin, with commercially available antibodies.
Senior study author Bruce Spiegelman of Dana-Farber Cancer Institute and Harvard Medical school says that the confusion over irisin comes down to disagreement over how irisin protein is made in skeletal muscle cells and the detection limits
that does not rely on antibodies, to precisely measure how much irisin increases in people after exercise. he data are compelling
says endocrinologist Francesco Celi of the Virginia Commonwealth University Medical center, who was not involved with the study. mportantly,
#Telltale biomarker detects early breast cancer in NIH-funded study Researchers have shown that magnetic resonance imaging (MRI) can detect the earliest signs of breast cancer recurrence and fast-growing tumors.
breakaway tumor cells with the potential to develop into dangerous secondary breast cancer tumors elsewhere in the body.
Cleveland and was funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National institutes of health.
CWRU M. Frank Rudy and Margaret Domiter Rudy Professor of biomedical engineering and an expert in molecular imaging for cancer and other diseases. e showed with this technique that we can detect very tiny tumors of just
revealing smaller cancers than can be detected with current clinical imaging modalities. ur imaging technology has the potential to differentiate aggressive tumors from low-risk tumors.
These are two things that potentially can make a big impact on clinical practice and also management of cancer.
Since small, early-stage cancers are the most responsive to drug treatments, screening is an important aspect of follow-up care for breast cancer patients,
and early detection is critical in tailoring appropriate and effective therapeutic interventions. While multiple imaging techniques, including MRI,
they are neither able to detect specific cancer types or early cancer growth. The earliest signs of cancer spread are called micrometastases.
As the name implies, they are often too small to be detected with standard screening. Dr. Lu team used a biochemical approach combined with MRI to detect molecular changes that signal micrometastases.
More importantly, the fibronectin part of the complex is expressed during a cell transition to cancer and plays a role in cell growth
The researchers collected images depicting metastases where breast cancer had spread beyond the original tumors. Metal molecules within the contrast solution are magnetized during the MRI process
and enhance the image wherever the molecules of solution bind with the targeted protein. he primary tumor sends signals to distant tissue
generating enough signal for MRI detection of small, high-risk cancer and micrometastases. The researchers tested the approach in mice into
and tumors compared with normal tissue. Using a microscopic imaging approach, called cryo-imaging, and MRI, the researchers verified that the MRI technique could detect micrometastases,
and the consequence of metastatic cancer make these efforts urgent and important, said Lu, adding that his research team also hopes to advance the approach for prostate cancer detection. e think this targeted approach holds great promise for earlier imaging of high-risk cancers in the clinic.
It could also become useful as a noninvasive way to assess breast cancer treatment progress.
The team plans to complete safety testing of the imaging agent during the next three years.
Andreas Velten, a Morgridge medical engineering affiliate and scientist with the University of Wisconsin-Madison Laboratory for Optical and Computational Instrumentation (LOCI
Cerebrovascular disease often entails complex tangles of vessels in sensitive brain areas. hese children had unique anatomy with deep vessels that were very tricky to operate on,
Harvard Medical school associate professor of neurosurgery at Boston Children Hospital and senior author of the paper. he 3-D printed models allowed us to rehearse the cases beforehand
who co-directs the Cerebrovascular Surgery and Interventions Center at Boston Children. ou can physically hold the 3-D models,
and get tactile feedback. s described in the Journal of Neurosurgery: Pediatrics, the models were based on the children actual brain scans.
Data from the scans were used to program a 3-D printer that laid down synthetic resins layer by layer.
I practiced those steps ahead of time. he surgery went off without complications, and last month Adam had a clean one-year follow-up angiogram.
Darren Orbach, HMS associate professor of radiology and co-director of the Cerebrovascular Surgery and Interventions Center at Boston Children, treated a 2-month-old infant who had a rare vein of Galen malformation in
Orbach used an interventional radiology technique called embolization to seal off the malformed blood vessels from the inside. ven for a radiologist who is comfortable working with
, were created in collaboration with the Boston Children Hospital Simulator Program (SIMPEDS), directed by HMS associate professor of anesthesia Peter Weinstock, the paper first author.
Measurements of the models showed 98 percent agreement with the children actual anatomy. All four children malformations were removed successfully
surgeon and operating roomhose with 3-D models had their surgical time reduced by 30 minutes,
but even a 30-minute reduction is significant for children who are especially sensitive to anesthesia.
The SIMPEDS program is tracking use of 3-D printed models across Boston Children Hospital,
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