#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 this week 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.
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,
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
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,
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.
an we do it in the medical space??Industry partnerships work best hen we can actually collaborate to invent the future,
and while many of these are beneficial, some can cause disease. For example, some reports have linked Crohn disease to the presence of certain strains of E coli. e like to be able to remove specific members of the bacterial population
and see what their function is in the microbiome, Lu says. n the longer term you could design a specific phage that kills that bug
but more information about the microbiome is needed to effectively design such therapies. The paper lead author is Hiroki Ando, an MIT research scientist.
but efforts to harness them for medical use have been hampered because isolating useful phages from soil
so that simplifies that workflow in the lab. The new approach also overcomes an important hurdle in using bacteriophages to treat disease,
which makes it difficult to choose the right phage for the right infection, if such a phage is available at all,
who was involved not in the research. his is a big step in the development of phage therapies with predictable outcomes and a good demonstration of
what synthetic biology approaches will bring to medicine in the near future. A targeted strike In this study,
and gastrointestinal infections, including pneumonia, sepsis, gastritis, and Legionnairesdisease. One advantage of the engineered phages is that unlike many antibiotics,
Lu says. e aim to create effective and narrow-spectrum methods for targeting pathogens. Lu and his colleagues are now designing phages that can target other strains of harmful bacteria
as well as treating human disease. Another advantage of this approach is that all of the phages are based on an identical genetic scaffold,
The newly described Cpf1 system differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics,
including in cancer research, says Levi Garraway, an institute member of the Broad Institute, and the inaugural director of the Joint Center for Cancer Precision Medicine at the Dana-Farber Cancer Institute, Brigham and Women Hospital,
and the Broad Institute. Garraway was involved not in the research. An open approach to empower research Zhang,
These groups plan to offer licenses that best support rapid and safe development for appropriate and important therapeutic uses. e are committed to making the CRISPR-Cpf1 technology widely accessible,
Zhang says. ur goal is to develop tools that can accelerate research and eventually lead to new therapeutic applications.
unicorn fever has raised fears of a bubble in the private equity markets.""You have a frenzy of investors looking for the next Facebook.
#Self-assembling, bioinstructive collagen materials for research, medical applications A Purdue University researcher and entrepreneur is commercializing her laboratory's innovative collagen formulations that self-assemble
In addition, they can be used to create next generation tissue engineered medical products that foster improved tissue integration and regeneration.
Sherry Harbin, an associate professor in Purdue's Weldon School of Biomedical engineering and Department of Basic Medical sciences
and disease states such as cancer, "Harbin said.""Unfortunately, growth of cells in these oversimplified environments has been shown not to correlate well with human cell responses in the body.
including tumor metastasis and drug/toxin sensitivity.""This is important as pharmaceutical companies and regulatory agencies look for new,
This technology also is supporting the development of the first bioinstructive collagen-based therapeutics for medical applications,
including regenerative medicine strategies involving therapeutic cells, multifunctional drug delivery, surgical implants, and tissue engineered medical products.
Conventional biological products including collagen sponges require extensive chemical and physical processing to improve their mechanical strength
Geniphys plans to produce medical-grade collymer products for veterinary and medical applications, including wound and hemostatic dressings,
cell-instructive implants, engineered tissue and organ replacements, hybrid medical devices and therapeutic cell and molecule delivery.
Research into the nature of this process is of significant importance in biology and medical science.
This is expected to lead to medical treatments in various fields that can for example, prevent cancer cells from multiplying,
it can cause a range of life-threatening diseases such as cancer, autoimmune disorders, Alzheimer's and diabetes.
This patented technology will allow pharmaceutical companies to measure simultaneously a large number of compounds and select which one can be developed into drugs to fight against diseases.
The device was developed at Bath by researchers Dr Pedro Estrela and Phd student Nikhil Bhalla in the Department of Electronic & Electrical engineering, Dr Mirella Di Lorenzo in the Department of Chemical engineering,
and facilitate the development of new drugs for diseases like cancer, stroke and dementia.""The simplicity is the strength of this technology.
Greater accuracy requires a more precise measuring process as well as adjustable implants. Now, a new type of measurement method coupled with a modular implant should allow orthopedic surgeons to precisely calibrate leg length after the operation
so it matches its original length. The researchers will be introducing their development at the Medtec expo in Stuttgart, April 21-23.
Implant manufacturers face numerous challenges; for example, the artificial joints may eventually Break in addition, orthopedic surgeons currently have no suitable method for precisely measuring leg length before the operation
or for adjusting the implants accordingly. The result is that after the operation, the leg can actually be longer
or shorter than it used to be. This leads to problems with the spine, which have to be resolved using shoe inserts.
orthopedic surgeons will be able to measure their patients'leg lengths much more precisely. The Fraunhofer researchers collaborated on the new system with several project partners:
the Clinic for Orthopedics, Trauma Surgery and Plastic surgery at the Leipzig University Hospital; University of Applied sciences Zwickau and its Research and Transfer Centre;
AQ Implants Gmbh; and MSB-Orthopädie-Technik Gmbh.""The margin of error in our process is less than one centimeter,
"Currently, the usual procedure calls for the doctors to determine leg length with a tape measure,
With the patient in a prone position, the doctor affixes a small plastic box containing two LEDS to the patient's shin.
The doctor then takes hold of the patient's heel and lifts it upward. With that motion, the two lights trace an arc that is recorded by a camera positioned about 1. 5 meters to the side of the patient.
The doctor takes this measurement twice once right before the operation and once after the implant has been inserted temporarily.
The box remains on the leg during the operation. A software program compares both arcs to determine
If necessary, the doctor can make adjustments to the artificial hip. Initial testing of a measuring system prototype has met already with success at the Leipzig University hospital.
Unbreakable, adjustable hip implants Fraunhofer's researchers also optimized the hip implants, again working together with partners from industry, medicine and research."
"We've developed an implant that can be adjusted to each individual patient, "says Grunert. The trick was to do away with prefabricated implants in various sizes and use a modular system instead.
In this method, the doctor can select the right hip stem as well as the right neck for each patient.
Special screw connections are used to attach the individual parts to each other and the combined unit is implanted in the hip for testing.
The doctor now measures the leg length, and, if necessary, can easily separate the implant's various components to exchange them for better-fitting parts
or adjust them as required. Another advantage is that the artificial hip is less prone to breakage than conventional modular models with a conical clamping ring.
Currently, the doctor connects the stem and the neck of the prefabricated artificial hip during the operation with a well-placed stroke of the hammer.
This puts tremendous stress on the connection point, a conical clamping ring. Furthermore, once the parts have been joined together,
it's virtually impossible to separate and adjust them. That's not the case for the specialized screws that hold the parts of the new implants together.
The point where they connect is mechanically stable and prevents the implant from breaking. The new system was developed within the"artificial joints"cooperative network
which is funded by the Federal Ministry for Economic Affairs and Energy (BMWI) and coordinated by Fraunhofer IWU.
#Breakthrough finds molecules that block previously'undruggable'protein tied to cancer A team of scientists at the University of Kansas has pinpointed six chemical compounds that thwart Hur,
an"oncoprotein"that binds to RNA and promotes tumor growth. The findings, which could lead to a new class of cancer drugs,
thus blocking Hur function as a tumor-promoting protein, "said Liang Xu, associate professor of molecular biosciences and corresponding author of the paper.
The results hold promise for treating a broad array of cancers in people. The researcher said Hur has been detected at high levels in almost every type of cancer tested,
including cancers of the colon, prostate, breast, brain, ovaries, pancreas and lung.""Hur inhibitors may be useful for many types of cancer,
"Xu said.""Since Hur is involved in many stem cell pathways, we expect Hur inhibitors will be active in inhibiting'cancer stem cells,
'or the seeds of cancer, which have been a current focus in the cancer drug discovery field."
"Hur has been studied for many years, but until now no direct Hur inhibitors have been discovered, according to Xu.""The initial compounds reported in this paper can be optimized further
and developed as a whole new class of cancer therapy, especially for cancer stem cells, "he said."
"The success of our study provides a first proof-of-principle that Hur is druggable,
"A cancer-causing gene, or oncogene, makes RNA, which then makes an oncoprotein that causes cancer
or makes cancer cells hard to kill, or both,"Xu said.""This is the problem we're trying to overcome with precision medicine."
"The scientist said the Hur-RNA binding site is like a long, narrow groove, not a well-defined pocket seen in other druggable proteins targeted by many current cancer therapies."
"Hur tightly binds to RNA like a hand, "Xu said.""The Hur protein grabs the'rope'r the RNAT a site called'ARE'on the rope.
and involved the collaboration of chemists, cancer biologists, computer modeling experts, biochemists and biophysicists at KUOTABLY the labs of Xu, Jeffrey Aubé in the Department of Medicinal Chemistry and Jon Tunge in the Department of chemistry.
For Xu, the findings are reflective of a personal commitment to improving odds for people diagnosed with cancer
the second-largest killer in the U s. after heart disease.""Trained as medical doctor and Ph d.,with both a grandfather and an uncle who died of cancer,
I devoted my career to cancer research and drug discoveryiming to translate discovery in the lab into clinical therapy,
to help cancer patients and their families, "he said.""We hope to find a better therapynd eventually a cureor cancer. c
#Synthetic muscle ready for launch Rasmussen developed the material at RAS Labs and has worked closely with researchers
and engineers at the U s. Department of energy's Princeton Plasma physics Laboratory (PPPL) to develop the material's ability to adhere to metal.
The Synthetic Muscle could be used in robotics in deep space travel such as travel to Mars because of its radiation resistance."
She recently received a grant from the Pediatric Medical device Consortium at the Children's Hospital of Philadelphia to research this possibility.
Carman did so by working nights as a nurse. For Rasmussen, the launch is the culmination of her dreams."
One such instrument is the gas chromatography system used in a number of scientific, medical,
For example, wearable/biomedical devices and electronic skins (e skins) should stretch to conform to arbitrarily curved surfaces and moving body parts such as joints, diaphragms, and tendons.
These noteworthy results were achieved by the non-destructive stress-relaxation ability of the unique electrodes as well as the good piezoelectricity of the device components.
It can open avenues for power supplies in universal wearable and biomedical applications as well as self-powered ultra-stretchable electronics."
which could help curb the risk of unwanted infections in agricultural or garden plants, the team says.
an infection of Cryptosporidium parvum may mean nothing more than a few days of bad diarrhea. For someone with a compromised immune system,
it can mean death, following an excruciating, protracted bout of watery diarrhea. Recently, researchers at Fudan University's Institute of Biomedical sciences in Shanghai developed a lab-on-a-chip device that can rapidly diagnose cryptosporidium infections from just a finger prickotentially bringing point-of-care diagnosis to at-risk areas in rural China
in order to improve treatment outcomes. Worldwide treatment for the parasitic infection consists largely of oral rehydration
and managing symptoms until the body clears the infection, something that may take far longer for people with HIV infections.
Currently, China has more than 780,000 people living with HIV/AIDS, but there is very little data on how many of them are living with Cryptosporidium infections.
This stems from the difficulties of diagnosing an infection in the field-poor sensitivity and a short window of spore secretion both limit the viability of acid-fast staining,
a standard diagnostic assay in use today. More advanced immunoassays such as ELISA, are difficult to use broadly
because they require relatively advanced lab settings and skilled technicians. To address this need, Xunjia Cheng and Guodong Sui, both professors at Fudan University,
Cheng's research has involved medical protozoa and opportunistic HIV infections, and Sui's lab focuses on microfluidics.
pumps and columns, collectively sitting at the heart of a platform of reagent cartridges, an injection pump, a fluorescence microscope and a digital camera.
The microfluidic device tests for the presence of the parasites'P23 antigen, a major molecular target of host antibody responses against the pathogen's infective stages.
Sui and Cheng tested their device's efficacy at diagnosing Cryptosporidium infections in 190 HIV-infected patients in Guangxi, China.
Future work for Sui and Cheng involves expanding the chip's sample processing capacities to include other infectious diseases
Defects in this process can lead to cancer, genetic problems and premature aging. In a research paper published in the Journal of Cell biology, Alessandro Vindigni, Ph d.,professor in the Edward A. Doisy Department of Biochemistry and Molecular biology at Saint louis University
Lesions in DNA can occur as often as 100,000 times per cell per day. They can be the result of normal metabolic activities, like free radicals,
Improper repair of DNA lesions can lead to mutations, abnormal chromosome structures, or loss of genetic information that in turn can cause premature aging, cancer, and genetic abnormalities.
Depending on the degree of genome instability these alterations will determine whether a cell survives, goes into a growth-arrest state, or dies.
If the cell's replication machinery collides with the lesion, a strand break can occur."
"Or, a serious lesion may be tolerated and the cell will continue to replicate. This may or may not be a good decision,
as this can lead to cancer. It is the degree of genomic instability caused by the lesion that will determine
whether the cell will survive.""While these scenarios pose serious threats, our cells have evolved elegant mechanisms to cope,
"Sometimes, these forks run into obstacles-like the lesions described above-that block their progress. When they do,
"Fork reversal is a central mechanism that our replication machinery uses to deal with DNA lesions,
and collision with the lesion is prevented.""In this study, Vindigni and team have identified new enzymes that enable cells to resume replication once the DNA lesion has been repaired.
Vindigni found that DNA2, an enzyme that works both as a nuclease (an enzyme that degrades DNA)
and highlight top biomedical research. Vindigni's group also contributed to a second paper that was published as back-to-back in the same issue of the Journal of Cell biology on the role of a key homologous recombination factor in the formation of reversed replication forks:
Digital imaging is expected to enable many emerging fields including wearable devices, sensor networks, smart environments, personalized medicine,
A team from Massachusetts General Hospital investigating bone loss during bed rest, in microgravity or through diseases such as osteoporosis, will use the Alvetex Scaffold in experiments 150 miles above the surface of the Earth after the equipment is delivered by the Spacex Dragon capsule.
The experiment seeks to understand how the effects how physical forces such as gravity affect the biochemistry of bone cells
and could lead to better treatments for diseases such as for osteoporosis. BBSRC-funded research by Professor Stefan Przyborski
showing structural stress corrosion cracking and wing panel composite skin abnormalities, engineers have had to do extensive analysis to develop repairs."
"So the need for certifying a new material comes in, "says Michopoulos, "and says,'How are we going to compare a new material and,
and pursued postdoctoral research in multiphysics, fracture mechanics, and applied mathematics at Lehigh University. When he tells how he came to be at NRL in 1986,
#New synthetic technology for medicines and fine chemicals A University of Tokyo research group has succeeded in synthesizing (R)- and (S)- rolipram, the active component of a medicine,
in high yield with high selectivity by an innovative catalyzed flow fine synthesis instead of the traditional batch method used in the production of 99%of medicines.
the active components of medicines as well as other fine chemicals are synthesized by a repeated batch reaction method, in
Professor Kobayashi says"This new technology can be applied to not only other gamma aminobutyric-acids acids and medicines but also various chemicals such as flavors, agricultural chemicals,
developed by Albert Einstein College of Medicine biologist Robert Singer, uses fluorescent probes made of DNA
and identify areas of DNA responsible for desirable traits such as high yield or disease resistance. Crop breeding programmes can make use of this genetic information to ensure that the preferred trait is inherited by future crop yields,
and applied in a research project where it identified genetic markers that signal resistance to the wheat yellow rust pathogen (Puccinia striiformis f. sp. tritici).
This disease is responsible for devastating bread wheat crops and has developed'Warrior'strains capable of infecting individuals previously believed to have tolerance."
so it can be used in medicine, particle physics and material science. Terahertz radiation falls between the microwave and infrared portions of the electromagnetic spectrum (300 GHZ THZ),
Their anxiety is heightened only by the prospect of an imminent rise in U s. interest rates, which would draw capital away from emerging markets like China."
He centers his research on robotic systems and technologies that assist those in need due to advanced age or illness.
Massimiliano Zecca holds a Ph d. in Biomedical Robotics from the Scuola Superiore Santnna Pisa,(Italy),
He is a member of the National Centre for Sport and Exercise Medicine in the East midlands,
and of the NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit. Zecca M. IJARS Video Series:
Medical devices designed to reside in the stomach have a variety of applications, including prolonged drug delivery, electronic monitoring,
However, these devices, often created with nondegradable elastic polymers, bear an inherent risk of intestinal obstruction as a result of accidental fracture or migration.
Now, researchers at MIT Koch Institute for Integrative Cancer Research and Massachusetts General Hospital (MGH) have created a polymer gel that overcomes this safety concern
which is a medical emergency potentially requiring surgical intervention, says Koch Institute research affiliate Giovanni Traverso,
as there is a greater risk for fracture if a device is too large or too complex.
a professor of medical science and engineering at Brown University who was not involved with this study. his is a very smart approach.
patientsadherence to long-term therapies for chronic illnesses is only 50 percent in developed countries, with lower rates of adherence in developing nations.
Medication nonadherence costs the U s. an estimated $100 billion every year, the bulk of which comes in the form of unnecessary hospitalizations.
The researchers also say that single-administration delivery systems for the radical treatment of malaria
and other infections could significantly benefit from these technologies. In a March 2015 commentary piece in Nature, Traverso and Langer wrote that the GI TRACT is an area rife with opportunity for prolonged drug delivery in tackling this global health problem.
With this new material which can be used to create extended-release systems via swallowable ills,
they envision an emerging field of orally delivered devices that can maximize adherence and therapeutic efficacy.
#Researchers Reveal 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 this week 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.
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,
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
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,
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.
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