FDA Adopts Three Nanotechnology Standards

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The U.S. Food and Drug Administration (FDA) recently adopted three nanotechnology standards as part of a major update to the administrations List of Recognized Standards. The documents comprise a Technical Specification (TS) developed by the International Organization for Standardization (ISO) Technical Committee (TC) 229 on Nanotechnologies, and two standards developed by ASTM International (ASTM), a member of the American National Standards Institute (ANSI) and ANSI-accredited Standards Developer.

ISO/TS 14101, Surface characterization of gold nanoparticles for nanomaterial specific toxicity screening: FT-IR method, adopted by the FDA in January 2015, was developed by ISO TC 229, WG 3, Health, safety, and environment, under U.S. leadership. At the time of the documents publication, Dr. Laurie Locascio of the National Institute of Standards and Technology (NIST) served as the WG 3 Convenor, and Dr. Nam Woong Song of Korea served as the project leader. The U.S.s Dr. Vladimir Murashov of the National Institute for Occupational Safety and Health (NIOSH) currently serves as WG 3 Convenor.

ISO/TC 229 Nanotechnologies defines nanotechnology as application of scientific knowledge to manipulate and control matter predominantly in the nanoscale (approximately 1 nm to 100 nm) to make use of size- and structure-dependent properties and phenomena distinct from those associated with individual atoms or molecules, or extrapolation from larger sizes of the same material. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modeling and manipulating matter at this length scale.

One of ISOs most active committees, ISO/TC 229 focuses on the development of nanotechnology standards, including those for terminology and nomenclature; metrology, and instrumentation, test methodologies; modeling and simulations; and science-based health, safety, and environmental practices. To ensure the U.S. is strongly represented throughout TC 229s areas of activity, the ANSI-accredited U.S. Technical Advisory Group (TAG) to ISO TC 229, administered by ANSI , formulates and delivers U.S. positions and proposals to ISO in all areas of nanotechnology. Mirroring ISO TC 229s four-WG structure, the U.S. TAG is made up of U.S. private- and public-sector experts in nanotechnology who serve as delegates for ISO TC 229 meetings, with Steve Brown of Intel Global Environmental Health and Safety serving as overall TAG Chair.

The FDA advises referring to the relevant documents for points to consider when assessing whether an FDA-regulated product involves the application of nanotechnology. Among the various properties of gold nanoparticles (Au NPs), surface ligand characteristics are found to play an important role in determining the behavior of Au NPs, including the aggregation/agglomeration properties of Au NPs in solution, protein binding of these particles to surfaces in cell culture media, and toxicity of Au NPs to living cells.

The FDAs other adopted standards, ASTM E2490, Standard Guide for Measurement of Particle Size Distribution of Nanomaterials in Suspension by Photon Correlation Spectroscopy (PCS), and ASTM E2535, Standard Guide for Handling Unbound Engineered Nanoscale Particles in Occupational Settings, were developed by ASTMs Committee E56 on Nanotechnology.

More detailed information on all three documents referenced can be found in the ANSI-NSP Nanotechnology Standards Database at Nanostandards.ansi.org. For more information regarding either the ANSI-NSP or ANSI-Accredited U.S. TAG to ISO/TC 229, contact Ms. Heather Benko (senior manager, nanotechnology standardization activities, hbenko@ansi.org).

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The American National Standards Institute (ANSI) is a private non-profit organization whose mission is to enhance U.S. global competitiveness and the American quality of life by promoting, facilitating, and safeguarding the integrity of the voluntary standardization and conformity assessment system. Its membership is made up of businesses, professional societies and trade associations, standards developers, government agencies, and consumer and labor organizations. The Institute represents the diverse interests of more than 125,000 companies and organizations and 3.5 million professionals worldwide.

The Institute is the official U.S. representative to the International Organization for Standardization (ISO) and, via the U.S. National Committee, the International Electrotechnical Commission (IEC), and is a U.S. representative to the International Accreditation Forum (IAF).

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FDA Adopts Three Nanotechnology Standards

Together, nanotechnology and genetic interference may tackle 'untreatable' brain tumors

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Tel Aviv University researchers' groundbreaking strategy stops brain tumor cell proliferation with targeted nanoparticles

There are no effective available treatments for sufferers of Glioblastoma multiforme (GBM), the most aggressive and devastating form of brain tumor. The disease, always fatal, has a survival rate of only 6-18 months.

Now a new Tel Aviv University study may offer hope to the tens of thousands diagnosed with gliomas every year. A pioneer of cancer-busting nanoscale therapeutics, Prof. Dan Peer of TAU's Department of Department of Cell Research and Immunology and Scientific Director of TAU's Center for NanoMedicine has adapted an earlier treatment modality -- one engineered to tackle ovarian cancer tumors -- to target gliomas, with promising results.

Published recently in ACS Nano, the research was initiated by Prof. Zvi R. Cohen, Director of the Neurosurgical Oncology Unit and Vice Chair at the Neurosurgical Department at Sheba Medical Center at Tel Hashomer. The Israeli Cancer Association provided support for this research.

Trying a new approach to gliomas

"I was approached by a neurosurgeon insistent on finding a solution, any solution, to a desperate situation," said Prof. Peer. "Their patients were dying on them, fast, and they had virtually no weapons in their arsenal. Prof. Zvi Cohen heard about my earlier nanoscale research and suggested using it as a basis for a novel mechanism with which to treat gliomas."

Dr. Cohen had acted as the primary investigator in several glioma clinical trials over the last decade, in which new treatments were delivered surgically into gliomas or into the surrounding tissues following tumor removal. "Unfortunately, gene therapy, bacterial toxin therapy, and high-intensity focused ultrasound therapy had all failed as approaches to treat malignant brain tumors," said Dr. Cohen. "I realized that we must think differently. When I heard about Dan's work in the field of nanomedicine and cancer, I knew I found an innovative approach combining nanotechnology and molecular biology to tackle brain cancer."

Dr. Peer's new research is based on a nanoparticle platform, which transports drugs to target sites while minimizing adverse effects on the rest of the body. Prof. Peer devised a localized strategy to deliver RNA genetic interference (RNAi) directly to the tumor site using lipid-based nanoparticles coated with the polysugar hyaluronan (HA) that binds to a receptor expressed specifically on glioma cells. Prof. Peer and his team of researchers tested the therapy in mouse models affected with gliomas and control groups treated with standard forms of chemotherapy. The results were, according to the researchers, astonishing.

"We used a human glioma implanted in mice as our preclinical model," said Prof. Peer. "Then we injected our designed particle with fluorescent dye to monitor its success entering the tumor cells. We were pleased and astonished to find that, a mere three hours later, the particles were situated within the tumor cells."

A safer, more promising approach

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Together, nanotechnology and genetic interference may tackle 'untreatable' brain tumors

Precision nano 'drones' deliver healing drug to subdue atherosclerosis

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VIDEO:Animation: Precision Nano "Drones " Deliver Healing Drug to Subdue Atherosclerosis. view more

NEW YORK, NY (February 18, 2015) - Nanometer-sized "drones" that deliver a special type of healing molecule to fat deposits in arteries could become a new way to prevent heart attacks caused by atherosclerosis, if a recent study in mice by scientists at Columbia and Harvard universities is a guide. Full findings appear in the February 18 online issue of Science Translational Medicine.

In the study, biodegradable nanoparticles--loaded with a molecule that promotes healing --were injected into mice with advanced atherosclerosis. The nanoparticles were designed to home in on the hot spots of atherosclerosis in the arteries.

About 70 percent of the nanoparticles implanted themselves into atherosclerotic plaques and slowly released the drug. In these mice, the damage to the arteries was repaired, leading to a plaque that, in humans, would be less likely to cause heart attacks.

Atherosclerosis is driven by inflammation that is uncoupled from the body's normal repair response. In essence, the fat-containing particles (called low-density lipoproteins, or LDL) that stick to our arteries act like splinters in our skin. But whereas skin is repaired once splinters are removed, LDL deposits can last indefinitely and healing never starts.

These inflamed and damaged hot spots are the reason why atherosclerosis causes heart attacks. The spots are prone to rupture, and when they do, blood clots form around the break and obstruct blood flow to the heart.

Many researchers are trying to develop drugs that prevent heart attacks by tamping down inflammation, but that approach has some downsides, says Columbia atherosclerosis researcher Ira Tabas, MD, Richard J. Stock Professor of Medicine (Immunology) and professor of pathology & cell biology, one of the study's two senior leaders.

"One is that atherosclerosis is a chronic disease, so drugs are taken for years, even decades. An anti-inflammatory drug that is distributed throughout the entire body will also impair the immune system's ability to fight infection," he says. That might be acceptable for conditions that severely affect quality of life, like rheumatoid arthritis, but "using this approach to prevent a heart attack that may never happen may not be worth the risk." [Tabas & Glass, Science 2013]

In addition, it's not enough to deliver an anti-inflammatory drug to the plaques, says Columbia associate research scientist Gabrielle Fredman, PhD, one of the study's lead co-authors. "Atherosclerosis is not only inflammation; there's also damage to the arterial wall," she says. "If the damage isn't repaired, you may not prevent heart attacks."

Nature's way of starting repairs is with a suite of "resolving" molecules that extinguish inflammation and then initiate healing. Instead of packing the nanoparticles with anti-inflammatory drugs, Dr. Tabas's and Dr. Farokzhad's team packed them with pieces of a resolving protein called annexin A1.

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Precision nano 'drones' deliver healing drug to subdue atherosclerosis

SMALL CAP SHARE IDEAS: Midatech Pharma has ambitions to be a billion pound firm

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By Ian Lyall, Proactive Investors, For Thisismoney.co.uk

Published: 07:38 EST, 9 March 2015 | Updated: 08:48 EST, 9 March 2015

Midatech Pharma chief executive, Jim Phillips has big ambitions for the life sciences company which listed on AIM late last year.

He wants it to be one of the few success stories of the life sciences industry, which has had more than its fair share of failures over the past three decades.

The US has created some monsters of new wave medicines the grande dames Amgen and Genzyme and more recently Biogen Idec, Gilead and Celgene.

Big ambitions: Midatechis at the forefront of nano-medicine

While not strictly a biotechnology firm - as we'll see later, it is at the forefront of nano-medicine - Midatech still wants to emulate the American model.

Phillips is not shy in revealing this means building a business valued at billions of pounds rather than hundreds of millions or tens of millions as it is today.

To help it do this it recruited an institutional shareholder base that understands and backs the Midatech model.

At the IPO last December, which raised 32milllion of new money, it brought in the influential Neil Woodford, who used to run one of Britain's largest funds for Invesco but is now going it alone.

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SMALL CAP SHARE IDEAS: Midatech Pharma has ambitions to be a billion pound firm

Keeping atherosclerosis in-check with novel targeted inflammation-resolving nanomedicines

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Nanometer-sized "drones" that deliver a special type of healing molecule to fat deposits in arteries could become a new way to prevent heart attacks caused by atherosclerosis, according to a study in pre-clinical models by scientists at Brigham and Women's Hospital (BWH) and Columbia University Medical Center. These findings are published in the February 18th online issue of Science Translational Medicine.

Although current treatments have reduced the number of deaths from atherosclerosis-related disease, atherosclerosis remains a dangerous health problem: Atherosclerosis of the coronary arteries is the #1 killer of women and men in the U.S., resulting in one out of every four deaths. In the study, targeted biodegradable nano 'drones' that delivered a special type of drug that promotes healing ('resolution') successfully restructured atherosclerotic plaques in mice to make them more stable. This remodeling of the plaque environment would be predicted in humans to block plaque rupture and thrombosis and thereby prevent heart attacks and strokes.

"This is the first example of a targeted nanoparticle technology that reduces atherosclerosis in an animal model," said co-senior author Omid Farokhzad, MD, associate professor and director of the Laboratory of Nanomedicine and Biomaterials at BWH and Harvard Medical School (HMS). "Years of research and collaboration have culminated in our ability to use nanotechnology to resolve inflammation, remodel and stabilize plaques in a model of advanced atherosclerosis."

In this study, targeted nanomedicines made from polymeric building blocks that are utilized in numerous FDA approved products to date, were nanoengineered to carry an anti-inflammatory drug payload in the form of a biomimetic peptide. Furthermore, this peptide was derived from one of the body's own natural inflammatory-resolving proteins called Annexin A1. The way the nanomedicines were designed enabled this biological therapeutic to be released at the target site, the atherosclerotic plaque, in a controlled manner.

In mouse models with advanced atherosclerosis, researchers administered nanomedicines and relevant controls. Following five weeks of treatment with the nanomedicines, damage to the arteries was significantly repaired and plaque was stabilized.

Specifically, researchers observed a reduction of reactive oxygen species; increase in collagen, which strengthens the fibrous cap; and reduction of the plaque necrotic core, and these changes were not observed in comparison with the free peptide or empty nanoparticles.

"Many researchers are trying to develop drugs that prevent heart attacks by tamping down inflammation, but that approach has some downsides," said co-senior author Ira Tabas, MD, Richard J. Stock professor of Medicine (Immunology) and professor of Pathology & Cell Biology at Columbia. "One is that atherosclerosis is a chronic disease, so drugs are taken for years, even decades. An anti-inflammatory drug that is distributed throughout the entire body will also impair the immune system's ability to fight infection." That might be acceptable for conditions that severely affect quality of life, like rheumatoid arthritis, but "using this approach to prevent a heart attack that may never happen may not be worth the risk."

In addition, it's not enough to deliver an anti-inflammatory drug to the plaques, said Columbia associate research scientist Gabrielle Fredman, PhD, one of the study's lead co-authors. "Atherosclerosis is not only inflammation; there's also damage to the arterial wall. If the damage isn't repaired, you may not prevent heart attacks."

The targeted nanomedicines used in this current study were engineered by researchers at BWH. Following preliminary proof-of-principle studies at Columbia University in models of inflammation, they were further tested in a clinically relevant disease model in mice and were shown to be capable of maneuvering through the blood circulation, and traversing leaky regions through to the inside of the plaques, as was demonstrated by fluorescence microscopy imaging of the plaque lesions.

Researchers note that in addition to their specific 'sticky' surfaces, their small sub-100 nanometer size is also a key property that facilitates the retention and accumulation of these nanoparticles within the plaques. These nanoparticles are 1000 times smaller than the tip of a single human-hair strand.

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Keeping atherosclerosis in-check with novel targeted inflammation-resolving nanomedicines

Heating targeted cancer drugs increases uptake in tumor cells

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Manchester scientists have found that gentle heating of targeted nano-sized drug parcels more effectively in deliver them to tumour cells - resulting in an improvement in survival rates.

One of the clinically-established methods for the delivery of cancer chemotherapy drugs has been to package the drug inside nano-sized containers, known as liposomes. This allows the drug to more effectively localise into cancer tissue and reduces side-effects by limiting drug-infused liposome uptake in healthy cells.

The effectiveness of these liposomes has been further improved by engineering them to contain molecules (monoclonal antibodies) on their surface that allow them to better target cancer cells in combination to making them temperature-sensitive so that they release their therapeutic drug content upon mild heating.

Researchers from the Nanomedicine Laboratory at The University of Manchester - part of the Manchester Cancer Research Centre - looked at the benefits of combining both active targeting and temperature-triggered release.

Professor Kostas Kostarelos, who led the research, said: "We have previously seen promising results from this combination approach on a petri dish, but no study had yet investigated its potential in living tissue."

The team compared liposomes with and without the ability to actively target cancer cells. They found that in combination with mild heating, the actively targeted liposomes showed greater uptake in tumour tissue in mice than those without targeting ability.

This resulted in a moderate improvement in the animals' survival.

"We have successfully developed heat-activated and antibody-targeted liposomes to show that they are chemically and structurally stable. This approach may help us develop novel mechanistic strategies to improve targeted drug delivery and release within tumour tissue, while better sparing normal cells," added Professor Kostarelos.

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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England v Bangladesh, Cricket World Cup 2015: as it happened

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Two of the things that are lacking from this England team are 1) individual match-winners and 2) inspiring, energetic leadership at all levels. At the moment that probably goes for the Test side too. I hope they can find both before the Ashes series or it will be another debacle.

13.51 Andrew Barnes looks to the future

If the ECB are to make changes then surely nothing is going to happen until Graves and Harrison take charge in May anyway. The current hierarchy are really lame ducks now, certainly not in a position to make the big calls. Theyre just filing the paperwork and checking the sponsorship money is paid on time. Possibly not Downton, but how tenable is his position given this outcome and the water thats gone under his bridge over the past twelve months?

If Moores goes, Downton has to go too. It was his call as was effectively sacking Kevin Pietersen. He can't be credible having wasted so much time and money on a false start.

13.47 One of England's best ODI batsmen has his say on Moores' assertion that England are missing a certain batsman. No, not that one ...

13.43 Here's Mike Buckley's verdict

This cricket team are more embarrassing than our footballers. Something I never thought would type.

They were for much of my life, Mike. It's the failure to be bold that is most objectionable. Anyone can fail but they do it so meekly. Every time in this format.

Joe Roberts wonders

What have England got against picking spinners? They're obsessed with stats yet they won't pick Tredwell when he's been the most consistent bowler in ODI's for the last few years. Surely the selectors know he averages 27 with the ball at a good economy rate of 4. Spinners are crucial in the middle overs to slow run rate, create pressure and pick up wickets.

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You can't take your genes with you: Strategies to share genetic information after death

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Does the child of a person with a heritable form of cancer have the right to access their parent's genetic information after death? What if no consent was ever established? In the March 2 issue of Trends in Molecular Medicine, biomedical ethicists review current arguments about how to disclose genetic information of the deceased and offer suggestions that may help clinicians and officials develop their own policies.

A number of arguments exist both for and against such postmortem disclosure. Disclosure could promote a relative's health or well-being and could help them take more control over their lives. At the same time, it could also violate family members' right not to know and could cause psychological, financial, or other harm. Disclosure efforts might also face logistical challenges as healthcare professionals work to contact, inform, and counsel at-risk relatives.

"The first question that comes to mind is whether a clinician should communicate findings at all," says lead author Sarah Boers, MD, a PhD candidate at the University Medical Center Utrecht in The Netherlands. "This could mean a breach of confidentiality; however, we conclude that sometimes findings are so important that this overrides confidentiality."

Second, should the clinician only communicate findings if family members ask for it, or should they actively approach family members to inform them? "For now, it is too far-reaching to actively approach family members, for example because of confidentiality and a family member's interest in not knowing," Boers says. "In addition, more public awareness about new sequencing techniques should be raised first, and proper guidelines should be developed."

Boers and her colleagues argue for passive postmortem disclosure policies, meaning that under certain circumstances access to genetic information should be provided to a deceased patient's family members at their request. They recommend that policies be crafted by clinicians and clinical institutions, as well as by professional, national, and ethics committees. The investigators also propose some urgent topics for further research, including patients' and family members' attitudes towards communication of genetic findings after death. Cultural differences across countries may make it inappropriate to adopt a single international policy.

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Trends in Molecular Medicine, Boers et al.: "Postmortem disclosure of genetic information to family members: active or passive?"

Trends in Molecular Medicine (TMM), published by Cell Press, is a monthly review journal that facilitates communication between groups of highly trained professionals with distinct backgrounds and skills, whose common goals are to understand and explain the molecular basis of disease with a view to new clinical practice. For more information, please visit http://www.cell.com/trends/molecular-medicine. To receive media alerts for TMM or other Cell Press journals, please contact press@cell.com.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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A new opportunity to treat drug-resistant leukemia discovered

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A public-private research collaboration leads to an unexpected discovery in patients with drug-resistant leukemia

Helsinki - February 9, 2015 - A study led by researchers at the Institute for Molecular Medicine Finland FIMM and Faculty of Medicine, University of Helsinki and the Helsinki University Central Hospital Comprehensive Cancer Center, in close collaboration with researchers at Pfizer, has identified a previously unrecognized action of Pfizer's axitinib as a potent inhibitor of the dominant mutation that confers drug resistance to all well tolerated treatments in patients with certain types of leukemia. The findings of this international joint effort were published online today, 9 February, 2015, in the journal Nature.

The FIMM research team studied cancer cells from patients with chronic myelogenous and acute lymphoblastic leukemia (CML and ALL) that had developed resistance to currently available treatments. These cancers are driven by the BCR-ABL1 fusion protein, and resistance to treatment developed due to a new genetic mutation in the BCR-ABL1 fusion gene in the cancer cells.

There were two critical factors that were integral to the outcome of this study. First, the Drug Sensitivity and Resistance Testing (DSRT) method developed at FIMM made it possible to study the response of these cancer patients' leukemia cells to a large panel of drugs simultaneously, thus identifying axitinib as a promising drug candidate. Using this approach, the researchers found that axitinib, a tyrosine kinase inhibitor currently approved to treat certain patients with advanced renal cell carcinoma, effectively eliminated these patient-derived drug resistant leukemia cells.

"This screening method is a key component of FIMM's Individualized Systems Medicine strategy. The drug panel covers all approved and many emerging cancer therapeutics, and thus enables an individualized selection of potentially effective therapies for leukemia patients," explains Krister Wennerberg, FIMM-EMBL Group Leader and a corresponding study author.

Second, by coupling this screening method with Pfizer's deep oncology and structure-based drug discovery expertise, the researchers were also able to define the mechanism by which axitinib binds to the drug resistant version of the BCR-ABL1 protein, providing fundamental new molecular insights into how cancer causing kinases can be blocked.

"If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key. In the case of axitinib, it acts as two distinct keys - one for renal cell carcinoma and one for leukemia" says Brion Murray, Pfizer Research Fellow and one of the lead authors of the study.

"Since axitinib is already used to treat cancer, its safety is known and a formal exploration of its clinical utility in drug resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened," says Kimmo Porkka, Head of Hematology at Helsinki University Central Hospital Comprehensive Cancer Center and one of the lead authors.

"Our findings highlight the power of drug repositioning, in other words, searching for novel uses for existing, emerging and abandoned drugs. This study shows what can be achieved when academic institutions and pharmaceutical companies team up to study effects of drugs using cells directly obtained from patients," says Olli Kallioniemi, the Director of FIMM.

"This high caliber publication is a great example of Pfizer's strong collaboration with academia to further advance research for patients with cancer," adds Murray. "Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias."

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A new opportunity to treat drug-resistant leukemia discovered

Frederick Alt of Harvard University and Boston Children's Hospital Awarded 2015 Szent-Gyorgyi Prize for Progress in …

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BETHESDA, Md., Feb. 26, 2015 /PRNewswire-USNewswire/ --The National Foundation for Cancer Research (NFCR) announced today that Frederick Alt, Ph.D., Professor of Genetics at Harvard Medical School, Director of the Program in Cellular and Molecular Medicine at Boston Children's Hospital, and Howard Hughes Medical Institute Investigator has been awarded the 2015 Szent-Gyrgyi Prize for Progress in Cancer Research. Dr. Alt's groundbreaking work in cancer genetics over four decades has helped to shape the very roots of modern cancer research. Today, that work continues to bear fruit, profoundly impacting the approaches that doctors use to diagnose and treat cancer.

NFCR's selection committee was unanimous in its decision to recognize Dr. Alt, whose work has proved foundational to the modern understanding of cancer not only how the lethal disease forms, but also how it can become resistant to treatment. In particular, his seminal discoveries of gene amplification and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically-targeted therapy and personalized medicine.

"Dr. Alt has been a consistently outstanding scientist throughout his career, and this award recognizes his entire body of work," said Dr. James Allison, Executive Director of the Immunotherapy Platform at MD Anderson Cancer Center, winner of the 2014 Szent-Gyrgyi Prize, and Chair of this year's Prize Selection Committee. "The genetic processes he described are central to understanding the mechanisms that cause cancer, and have ultimately led to an entire class of targeted therapy and associated diagnostics that are providing benefit to countless cancer patients."

Dr. Alt's discovery of gene amplification in chemotherapy-resistant cancer cellswhich revealed that cells can produce multiple copies of a genewas revolutionary, coming at a time when the human genome was widely believed to be stable and inflexible. This radical new concept suggested that cancer cells could change their genes, a process that would both allow them to develop more potent cancer-causing genes as well as evolve resistance to treatment. Dr. Alt proved the generality of his initial discoveries when he showed that the gene n-myc is commonly amplified in the childhood cancer neuroblastoma. Today, genomic instability is recognized as one of the hallmarks of cancer.

Equally important is Dr. Alt's work on the critical DNA repair mechanism called "non-homologous end joining" (NHEJ). Dr. Alt not only made the initial experimental findings that led to the discovery of this pathway, but also carried out an ingenious series of experiments over many years in his lab in Boston, taking it apart piece by piece to understand how it works. This work linked NHEJ to protecting against a specific kind of DNA damage called "translocations," which is a major component of many cancers, especially leukemia and lymphoma.

Both amplified genes and translocated genes are key components of the Precision Medicine paradigm, which is at the heart of 21st century medicine. By identifying the source of genetic abnormalities that drive both cancer development and drug resistance, Dr. Alt's insights helped to revolutionize cancer diagnostics and treatment. His discoveries led to a wholly new approach to treating cancer identifying these genetic abnormalities then selecting new drugs that target each specifically.

"I am truly honored to be selected by the National Foundation for Cancer Research to receive this award, and I am humbled to stand with past winners of the Szent-Gyrgyi Prize," said Dr. Alt. "Cancer is a complex and terrible disease, but with each new discovery we are making it less mysterious, more understandable, and ultimately less deadly. We are making progress."

"Dr. Alt's work has uncovered and explained some of the most foundational chemistry of life, and throughout his career he has always been focused on the implications for cancer. His vision and talent were instrumental in bringing cancer research into the modern era, and we are proud to present him with this award," said Sujuan Ba, Ph.D., Co-chair of the 2015 Szent-Gyrgyi Prize Selection Committee and President of NFCR.

Dr. Alt will be honored at an award ceremony held April 29, 2015 at The National Press Club in Washington, D.C. Media and the public are invited and encouraged to attend.

About the Szent-Gyrgyi Prize for Progress in Cancer Research

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ACMG Issues New Joint Guidelines for Determining Disease-Causing Potential of DNA Sequence Variations in Genetics in …

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BETHESDA, Md., March 5, 2015 /PRNewswire-USNewswire/ -- In an effort to standardize interpretation and reporting of genomic test results, the American College of Medical Genetics and Genomics (ACMG), together with colleagues from the Association for Molecular Pathology (AMP) and the College of American Pathologists (CAP), has developed an evidence-based gene variant classification system and accompanying standard terminology.

The new system, published online ahead of print in ACMG's flagship journal, Genetics in Medicine, is designed to assist genetic testing laboratories and clinical geneticists in the critical task of assigning the disease-causing potential to the many different genetic variants that individuals have in their DNA.

"These updated guidelines provide a systematic and sound way to classify genomic variants so that when Lab A on the east coast and Lab B on the west coast are reporting results, they are using the same method to classify that variant," said Sue Richards, Ph.D., a medical director of the Knight Diagnostic Laboratories, and Professor of Molecular and Medical Genetics at Oregon Health & Science University, Portland, OR. and chair of the workgroup that issued the guidelines. To develop the guidelines the multi-disciplinary workgroup sought input from the clinical genetics community through surveys and workshops at professional society meetings. The result is a consensus document that reflects that input.

"In the past, standard terms such as 'pathogenic' and a consistent strategy for classifying variants have been lacking," Richards said, "leading to wide variation in how laboratories classify individual differences in DNA sequence. Each person carries many thousands of these DNA variants, but determining which of these are causative for disease is a difficult task that requires an abundance of scientific evidence."

"Navigating the complexity of genetic evidence and how to weigh the strength of that evidence is challenging for laboratories and this guidance will help provide a consistent framework for that process," said Heidi Rehm, Ph.D., Chief Laboratory Director at Partners Laboratory for Molecular Medicine and Associate Professor of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Mass., and workgroup co-chair. "Although these guidelines were targeted to clinical laboratories, it is our hope that the same consistent approaches will be applied in the research setting and help improve the quality of published literature and the genetic claims being made."

"Recently, clinical laboratories have more broadly begun sharing their variant interpretations in the public domain through ClinVar, a database that aggregates information about genetic sequence variation and its relationship to human health and human disease, allowing differences of interpretation to be identified. Through this process, laboratories are employing the ACMG guidelines as a best standard in resolving any differences in variant interpretation," said Rehm.

Because genomics is a developing field of research, standards of evidence are also evolving over time and will continue to evolve. Many genetic changes are what's termed "variants of uncertain significance," (VUS), which simply means that not enough is known about them to be able to state whether they cause health problems or not. Under the new guidelines, a variant of uncertain significance (VUS) should not be used in clinical decision-making.

The guidelines provide five standard classifications: "pathogenic," "likely pathogenic," "uncertain significance," "likely benign," and "benign," along with standard definitions for each term. These new standards may place more variants in the VUS category, Richards said, because there is not enough scientific evidence to state with confidence that they do or do not cause disease.

The workgroup stresses that physicians should combine genomic results with other evidence of disease whenever possible. "Likely pathogenic" results provide enough evidence that a physician can act on it when combined with, for example, prenatal ultrasound, enzyme assays, physical findings or imaging studies.

It is important to note that these new guidelines cover only genetic variants that are inherited, not those genetic changes that arise in a specific cell within a tumor. Neither do the guidelines cover genetic changes that may contribute to complex diseases such as diabetes or heart disease. Guidelines for the interpretation of complex disease traits remain under study.

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ACMG Issues New Joint Guidelines for Determining Disease-Causing Potential of DNA Sequence Variations in Genetics in ...

JMD publishes article on laboratory perspective of incidental findings reporting

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AMP incidental findings working group recommends that laboratories develop individual policies for analysis and reporting of known and predicted incidental findings

Bethesda, MD, February 12, 2015 The Association for Molecular Pathology (AMP), the premier global, non-profit organization serving molecular laboratory professionals, announced that The Journal of Molecular Diagnostics today published a Special Article titled, "Reporting Incidental Findings in Genomic Scale Clinical Sequencing - A Clinical Laboratory Perspective." This paper offers new and important perspectives from the laboratory highlighting the need for increased understanding and transparency of complex genomic testing. It also outlines important recommendations, including the need for laboratories to establish clear and patient-friendly policies for delivering ancillary information generated from genome-wide genetic tests. A copy of the paper is available online at http://jmd.amjpathol.org/article/S1525-1578%2814%2900245-1/fulltext.

The AMP Incidental Findings Working Group, including authors of this paper, have closely followed the incidental findings debate since early 2013 when the American College of Medical Genetics (ACMG) published its guidelines on incidental findings reporting. These recommendations primarily focused on the content of secondary information obtained from genetic tests, and not the pitfalls of technology limitations, which has placed a significant burden on laboratories to educate patients as well as physicians about the strengths and limitations of genetic testing.

Lead author and Chair of the AMP Incidental Findings Working Group, Madhuri Hegde, Ph.D., from Emory Genetics Laboratory, Department of Human Genetics, Emory University, finds that patient and physician education about how genomic data are interpreted as well an appreciation for technology limitations placed on to the lab have been overlooked.

"Patients have a choice whether or not to receive additional information that may be available as a result of a genetic test that looks across an entire genome of DNA. In most cases, patients are interested in learning more, but it's critical that we educate them, as well as the ordering physician, about their options and what can and cannot be reported," noted Dr. Hegde. "While genetic testing technologies have revolutionized the way we diagnose and treat disease, we must appreciate the technical limitations that still exist today. If a report comes back with no known genetic abnormalities, it doesn't mean that a pathogenic variant might not exist - we just can't see it or interpret it from the data we have right now."

Laboratory regulation also plays an important role in how incidental findings are reported. Clinical Laboratory Improvements Amendments (CLIA) regulations, proficiency testing, lab accreditation, and other quality measures oversee and govern laboratories and the tests that they develop. If the U.S. Food and Drug Administration (FDA) steps in, as proposed in their recent draft framework, it could make access to important tests challenging.

"While we want to underscore the need for continued discussion among stakeholders to improve our understanding of the effect of different test result disclosure policies on patients, providers, and laboratories, we don't want to lose any progress that we have achieved since the completion of the human genome project," said Elaine Lyon, Ph.D., AMP Past President. "The proposed laboratory developed test regulation framework imposes substantially new requirements on clinical laboratories, hospitals, physicians, and other health care providers. This interference with the practice of medicine poses significant impact on patient access to vital molecular testing services necessary for improving patient care."

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About The Journal of Molecular Diagnostics

The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology, co-owned by the American Society for Investigative Pathology, and published by Elsevier, Inc., seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine.

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JMD publishes article on laboratory perspective of incidental findings reporting

One mum says she's baffled by daughter's selfie addiction

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More than 17 million selfies are uploaded to social media sites every week Here, 15-year-old Olivia Russell shares a day in her life as a selfie addict And her 49-year-old mother Tracy reveals her frustrations and fears of having daughter who documents and shares her every move on her phone

By Tracy And Olivia Russell For The Daily Mail

Published: 18:39 EST, 17 February 2015 | Updated: 19:45 EST, 17 February 2015

Selfie addict: Olivia Russell, 15, who lives with her parents Nigel and Tracy in Ashford, Kent

Every week, more than 17 million selfies are uploaded to social media websites mainly by teenagers. To understand the obsession, Femail asked 15-year-old Olivia Russell, a pony-mad, middle-class schoolgirl, to record a day in her life as a selfie addict. She lives with her parents, businessman Nigel, 50, and Tracy, 49, in Ashford, Kent. Here, her mother reveals the frustrations and fears of having a daughter who documents and shares her every move on her phone...

Tracy says: I doubt theres been a day in the past two years when I havent argued with my teenage daughter Olivia about the amount of time she spends taking selfies and posting them online.

Yes, I have a mobile phone, but I use it to make calls and thats it. This obsessive photograph taking is just beyond me. I dont understand it.

When I go to a restaurant and a lovely plate of food is placed in front of me, my first thought is: I cant wait to tuck in!

Olivias first thought is: I must take 12 pictures of it and upload it to six different media sites. Everything takes twice as long as it should do because shes always taking selfies. Just getting ready in the morning so I can drive her to school is a nightmare.

I feel as if I spend my whole life shouting Just get a move on! up the stairs or hammering on her bedroom door.

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Natural Belly Slimming Detox Capsule Medicine (30 Pounds In Just 30 Days) – Video

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How Mayo's "Dr. Google" Deal Disrupts Medicine

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Dr. Google Google has joined the Mayo Clinic, quietly signaling a powerful disruption for all of medicine.

Back in 1997 I wrote: The information age is to medicine as the Protestant Reformation was to the Catholic Church. The Church didnt disappear when information once held tightly by the priesthood became widely available, but religion changed forever.

My search engine, the doctor

In that context, Mayos agreement to produceclinical summaries under itsnamefor common Google medical searchesis like a medieval pope happily handing out Bible translations. The mission of the most-used search engine on the planet is to make the worlds information universally accessible and useful. Mayo, in contrast, has for decades been a global symbol of doctor-knows-best. Recommending a Google search as the first stop for those needing health information, in the words of a Mayo physician executive, represents a true paradigm change.

But theres much more going on here than search. From the Fitbit to medicines front lines, information technology is forcing a new doctor-patient relationship with new rules for new roles.

If information is power, digitized information is distributed power. While patient-centered care has been directed by professionals towards patients, collaborative health what some call participatory medicine or person-centric care shifts the perspective from the patient outwards.

Collaboration means sharing. At places like Mayo and Houstons MD Anderson Cancer Center, the doctors detailed notes, long seen only by other clinicians, are available through a mobile app for patients to see when they choose and share how they wish. mHealth makes the process mundane, while the content makes it an utterly radical act.

About 5 million patients nationwide currently have electronic access to open notes. Bostons Beth Israel Deaconess Medical Center and a few other institutions are planning to allow patients to make additions and corrections to what they call OurNotes. Not surprisingly, many doctors remain mortified by this medical sacrilege. Even more threatening is an imminent deluge of patient-generated health data churned out by a growing list of products from major consumer companies. Sensors are being incorporated into wearables, watches, smartphones and (in a Ford prototype) even a car that cares with biometric sensors in the seat and steering wheel. Sitting in your suddenly becomes telemedicine.

To be sure, traditional information channels remain. For example, a doctor-prescribed, Food and Drug Administration-approved app uses sensors and personalized analytics to prevent severe asthma attacks. Increasingly common, though, is digitized data that doesnt need a doctor at all. For example, a Microsoft fitness band not only provides constant heart rate monitoring, according to a New York Times review, but is part of a health platform employing algorithms to deliver actionable information and contextual analysis. By comparison, Dr. Google belongs in a Norman Rockwell painting.

These participative technologies have helped supercharge online patient communities, which by one estimate include about one in five Americans with a common chronic condition. Peer-to-Peer health care, as Pew calls it, has helped turn self-reported symptoms and therapeutic responses into crowd-sourced data points. Peers can also point the way to tools such as a consumer version of a sophisticated symptom checker or a medical-grade calculator of surgical risk. The aging of digital natives will only accelerate this trend.

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Penn Medicine: Brain activity can predict increased fat intake following sleep deprivation

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PHILADELPHIA - Experts have warned for years that insufficient sleep can lead to weight gain. A new Penn Medicine study found that not only do we consume more food following a night of total sleep deprivation, but we also we consume more fat and less carbohydrates and a region of the brain known as the salience network is what may lead us to eat more fat. The new findings are published in Scientific Reports.

Most research in this arena has focused on changes in metabolic hormones that lead to weight gain, while only a few have begun to examine how changes in brain activity may play a role. "We wanted to uncover whether changes in regional brain function had an impact on our eating behavior following sleep deprivation," says the study's senior author, Hengyi Rao, PhD, a research assistant professor of Cognitive Neuroimaging in Neurology and Psychiatry. "This work has implications for the approximately 15 million Americans who work the evening shift, night shift, rotating shifts, or other employer arranged irregular schedules."

The study took a unique approach and sequestered 34 sleep-deprived subjects and 12 controls in a sleep lab for five days and four nights for round-the-clock monitoring. All study subjects received one night of regular sleep and were then randomized to either total sleep deprivation or control for the remaining three nights. Baseline functional MRI (fMRI) to examine brain connectivity changes associated with macronutrient intake was conducted on all subjects the morning following the first night of sleep. Sleep-deprived subjects were matched to control subjects in age, body mass index (BMI), ethnicity or gender.

On the second night, sleep deprivation subjects were kept awake while the control subjects slept for eight hours. fMRI testing of both groups continued on days, two, three and four at the same time each day. All subjects had access to a variety of foods that they could consume as desired.

Sleep deprived subjects consumed close to 1,000 calories during overnight wakefulness. Despite this, they consumed a similar amount of calories the day following sleep deprivation as they did the day following baseline sleep. However, when comparing the macronutrient intake between the two days, researchers found that healthy adults consumed a greater percentage of calories from fat and a lower percentage of calories from carbohydrates during the day following total sleep deprivation.

The Penn researchers also found that sleep deprived subjects displayed increased connectivity within the "salience network," which is thought to play a role in determining contextually dependent behavioral responses to stimuli that can be either internal or external, and is one of several key brain networks that carry out various aspects of brain function. Moreover, increased connectivity in the salience network correlated positively with the percentage of calories consumed from fat and negatively correlated with the percentage of carbohydrates after sleep deprivation. The salience network is located toward the front of the brain and consists of three sections, the dorsal anterior cingulate cortex, bilateral putamen, and bilateral anterior insula. Activity in these structures is linked to both emotion and bodily sensations, such as the heart racing, stomach churning, pain, thirst, embarrassment, and attempting mental challenges. Changes in caloric intake and content after sleep deprivation may therefore relate to changes in the "salience" of food, and in particular fatty food, in individuals who are sleep deprived.

"We believe this is the first study to examine the connection between brain network connectivity and actual macronutrient intake after baseline sleep and after total sleep deprivation," says Rao. Most similar studies rely on self-reported hunger levels of food cravings, or on brain responses to pictures of different types of foods. "Although this study examined the effects of acute total sleep deprivation, similar changes may occur in response to the chronic partial sleep restriction that is so prevalent in today's society."

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Additional Penn authors on the study include Zhou Fang, Ning Ma, Senhua Zhu, Siyuan Hu and John A. Detre or the Center for Functional Neuroimaging; Andrea M. Spaeth, department of Sleep Medicine; and Namni Goel and David F. Dinges, division of Sleep and Chronobiology.

The study was funded by the National Institutes of Health (R01 HL102119, R01 NR004281, R21 DA032022, R03 DA027098, P30 NS045839, CTRC UL1RR024134), the department of the Navy, Office of Naval Research (N00014-11-1-0361) and a pilot grant from the Institute of Translational Medicine and Therapeutics at Penn.

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Keck Medicine of USC researchers trace origins of colorectal cancer tumor cells

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'Big Bang' model of tumor growth provides view into how to stop cancer before it starts

LOS ANGELES -- For the first time, Keck Medicine of the University of Southern California (USC) cancer researchers have traced the origins of colorectal cancer cells, finding important clues to why tumor cells become "good" or "bad," with the potential of stopping them before they start.

The scientists employed a "Big Bang" model of human colorectal cancer growth similar to the theory that the universe started from a single point and exploded outward. The team was led by Keck faculty researchers Darryl Shibata, M.D., professor of pathology, Keck School of Medicine of USC and Christina Curtis, Ph.D., M.Sc., assistant professor of medicine and genetics at Stanford University and adjunct assistant professor, department of Preventive Medicine, Keck School of Medicine of USC.

"It's like going back in time," said Shibata. "The history of each tumor is written in its genomes. To prevent tumors, you want to see what happened early on and how to stop their first cell divisions."

By taking samples from opposite sides of colorectal tumors, the researchers reconstructed the first few divisions, which took place when the nascent tumors were too small to even detect. The tumor starts were abnormal, with a burst of new mutations. Moreover, even from the start, many cancer cells expressed the abnormal mobility or intermixing of cells that would allow them to eventually invade and metastasize in the body. By contrast, tumor cells destined to form benign adenomas did not intermix, indicating that some tumors are "born to be bad."

Understanding which tumors will kill and which ones are harmless is critical to patients making decisions about tumor removal and surgery, Shibata said.

The next step is to further explore what happens at the genesis of tumor cells, which Shibata and Curtis are currently studying. Curtis will also look into whether other cancers behave the same way as the colorectal cancers.

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The research, "A Big Bang model of human colorectal tumour growth," will be published Monday, Feb. 9, 2015 in the peer-reviewed journal Nature Genetics.

Other USC researchers on the study include Andrea Sottoriva (now at the Institute of Cancer Research), Zhicheng Ma (now at Stanford University), Matthew P. Salomon, Junsong Zhao, Paul Marjoram, Kimberly Siegmund, and Michael F. Press. Researchers from the CHA Bundang Medical Center, University of California, San Francisco, and Queen Mary University of London also contributed to the research.

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CU School Of Medicine researchers offer new target for treating asthma

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AURORA, Colo. (Feb. 18, 2015) - Researchers have found a potential new target for treating asthma, according to a study led by researchers at the University of Colorado School of Medicine at the Anschutz Medical Campus and published in the journal Nature Communications.

About 10 million Americans and more than 300 million people worldwide have asthma. The most common therapies now used with asthma patients address airway muscle contractions triggered by inflammation, but those treatment results are often temporary or incomplete.

In the article in Nature Communications, Christopher Evans, PhD, associate professor of medicine at the CU School of Medicine, and his co-authors propose targeting other factors related to the overproduction of mucus, an often overlooked factor that causes breathing problems associated with asthma.

Specifically, Evans and his colleagues found that the protein Mucin 5AC (Muc5ac) plays a critical role in airway hyperreactivity, a characteristic feature of asthma that makes it difficult to breathe. In experiments with mice, the scientists found that genetic removal of Muc5ac eliminated airway hyperreactivity.

"The role of mucus as a cause of asthma has been misunderstood and largely overlooked," Evans said. "We found that it is a potential target for reducing obstruction in asthma."

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The research was supported by grants from the National Institutes of Health, the American Heart Association and the Crohn's and Colitis Foundation of America. Ten of the authors listed on the article are faculty at the CU School of Medicine.

About the University of Colorado School of Medicine

Faculty at the University of Colorado School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Health, Children's Hospital Colorado, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. The school is located on the Anschutz Medical Campus, one of four campuses in the University of Colorado system. To learn more about the medical school's care, education, research and community engagement, visit its web site.

Contact: Mark Couch, 303-724-5377, mark.couch@ucdenver.edu

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CU School Of Medicine researchers offer new target for treating asthma