Monthly Archives: March 2015

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

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

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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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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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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Penn study: OTC medications and supplements are most common causes of drug-induced liver failure

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Study upends common belief that prescription drugs are prime culprits in causing liver failure

IMAGE:This is David Goldberg, assistant professor of Medicine and medical director of Living Donor Liver Transplantation at the Perelman School of Medicine at the University of Pennsylvania view more

Credit: Penn Medicine

PHILADELPHIA - Drug-induced acute liver failure is uncommon, and over-the-counter medications and dietary and herbal supplements -- not prescription drugs -- are its most common causes, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The findings are published in the current issue of Gastroenterology.

One of the most feared complications of drugs and medications is acute liver failure, traditionally associated with a greater than 50 percent chance of dying without a liver transplant. Drug-induced liver injury, known as hepatotoxicity, is the second most common reason drugs are withdrawn from the market, behind cardiac toxicity, according to the U.S. Food and Drug Administration (FDA). The Penn authors, however, say this is based solely on abnormal liver tests, not actual liver damage. The real risk of acute liver failure that the researchers calculated was 1.61 per million people per year.

"Despite widely publicized cases of drug-induced acute liver failure related to acetaminophen and other medications, there are, until now, no studies to specifically evaluate the incidence of acute liver failure arising from drug-induced liver injury in the broader population," says senior author Vincent Lo Re, MD, MSCE, assistant professor of Medicine in the division of Infectious Diseases and assistant professor of Epidemiology in the Perelman School of Medicine at the University of Pennsylvania.

Lo Re and his team, including lead author, David Goldberg, MD, MSCE, assistant professor of Medicine and medical director of Living Donor Liver Transplantation at Penn, set out to uncover the incidence and outcomes of drug-induced acute liver failure in the United States through the analysis of data from an integrated healthcare system that is representative of the broader U.S. population.

They looked at data from Kaiser Permanente Northern California between January 1, 2004 and December 31, 2010, to assess the true impact of acute liver failure in the U.S.

Among the 5,484,224 patients evaluated, 62 were identified with acute liver failure, nearly half of which were drug-induced. Acetaminophen was implicated in 56 percent of cases, dietary/herbal supplements in 19 percent, antibiotics in 6 percent and miscellaneous medications in 18 percent.

Despite hepatotoxicity being the second most common cause of drug withdrawal from the market, acute liver failure, the most severe form of liver injury, from prescription drugs was rare, the team found. "We discovered that 75 percent of acute liver failure cases resulting from prescribed medication use were derived from over-the-counter products such as acetaminophen or herbal supplements," says Goldberg. "Prescription medications are an exceedingly rare cause of acute liver failure."

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Penn study: OTC medications and supplements are most common causes of drug-induced liver failure

WSU medical school bills take detour in House, Senate

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Bills that would give Washington State University the authority to start a medical school in Spokane have hit an unexpected detour.

OLYMPIA Bills that would give Washington State University the authority to start a medical school in Spokane bills that seemed on the fast track last week have hit an unexpected detour.

The House and Senate budget committees will hold hearings on the costs of a proposed medical school before legislative leaders will allow full votes in either chamber.

Supporters of the project said Tuesday its not a roadblock, but bill sponsors are surprised that legislation specifically rewritten to leave funding questions for later will need approval from the House Appropriations and Senate Ways and Means committees before facing full votes in each chamber.

We certainly hope the bill doesnt get caught up in overall budget negotiations, said Sen. Mike Baumgartner, R-Spokane.

Rep. Marcus Riccelli, D-Spokane, said the bills were written to split the discussion over a new medical school in Spokane. The first step was to rewrite state law to give WSU the authority to offer that medical education; the amount of money the state would provide for the school would be decided later.

State law currently restricts medical education to UW. The law, which has its roots in the Legislature settling a fight over education majors for the two institutions in 1917, is antiquated, Riccelli and Baumgartner both argue.

Companion bills in each chamber were amended to remove language that specifically directs the WSU regents to start a school, and instead merely give them the permission. Those passed out of each chambers Higher Education Committee last week with directions to go to the committees that schedule bills for a vote of the full chamber. A day or so later, they were rerouted to the budget committees.

The University of Washington has raised questions about past spending for its medical-school program in Spokane that was funneled through WSU when both schools were involved in the program. But thats reportedly not the reason the bills were referred to budget committees.

The nonpartisan legal counsel for the Senate Ways and Means Committee said the panel should consider the proposal because of its long-term budget implications, said Senate Majority Leader Mark Schoesler, R-Ritzville.

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WSU medical school bills take detour in House, Senate

Medical School to modify admissions requirements for 2017

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The University's Medical School is changing it up.

Beginning with prospective students entering in 2017, the Medical School has altered the admissions requirements for its applicants. Requirements previously included a list of eight courses in subjects such as organic chemistry and biochemistry. They now consist of qualities and experiences the Medical School looks for in its students.

Most of the new prerequisites are framed more broadly: rigorous experience in the humanities, academic strength and rigor in the fields of biology, chemistry and statistical methods and analysis; demonstrable knowledge of basic physical principles; and a clear and distinct experience in intellectual inquiry and active participation in the independent discovery of new knowledge.

Though these prerequisites may seem less specific than a list of classes, Rajesh Mangrulkar, associate dean for medical student education, expressed the opposite sentiment. He said the new requirements allow the admissions office to be more specific, telling the students the exact information the Medical School needs them to know prior to matriculation. He said listing a class title does not convey that information as effectively.

When you look at a course name, do you know what youre able to do because of having taken that course? Mangrulkar asked.

Steven Gay, assistant dean for admissions, also discussed the logic behind requiring proficiency in topics rather than class credit. He said the old requirements did not take into account that students may learn necessary material outside of the conventional classroom.

We see a number of students right now with advanced degrees, or who have spent extensive time in labs, Gay said. I think we should give students the opportunity if they are learning in those innovative and different ways not to have to repeat things unnecessarily.

Mangrulkar said the new application process is meant to create a dialogue in which students can reflect on how they have earned the knowledge they need, whether it be from a class or from another experience.

The student will be able to say, alright, these are the expectations, let me reflect on what Ive done and show how these all meet those different criteria, Mangrulkar said. Thats a better way to have a conversation than what weve had in the past, which is basically a student saying I took this class, is this okay?

Gay said that, though students have the freedom to gain knowledge in unique ways under the new requirements, taking classes is still the easiest way to fulfill the prerequisites.

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Medical School to modify admissions requirements for 2017

Education officials ask lawmakers to increase medical school funding past governor's proposal

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CARSON CITY, Nev. Nevada higher education officials on Tuesday asked legislators for three times more money than the governor has proposed to ramp up construction of a medical school in Las Vegas.

Nevada System of Higher Education officials presented their budget requests to a joint Assembly and Senate committee and asked for about $26 million for a medical school at the University of Nevada, Las Vegas.

In his proposed budget, Gov. Brian Sandoval allocated around $8.3 million over two years for the medical school. UNLV School of Medicine Dean Barbara Atkinson told lawmakers that increasing funding to $26.7 million over two years would help the school attract more donors and help with the accreditation process so it could begin accepting students in 2017.

"We're looking for a base of hard money support," Atkinson said. "Donors are going to feel very unsettled."

System of Higher Education Chancellor Dan Klaich also asked lawmakers for "bridge funding" for a number of rural community colleges and research institutions.

Great Basin College President Mark Curtis told lawmakers that changes to the state's funding formula meant the Elko-based school would see a reduction of $2 million from state allocations, after already cutting around $4 million in the past five years. Curtis said a one-time funding increase would help the college transition to a lower budget allocation.

"We're kind of at a pinch point relative to the funding formula," he said. "We believe it will take us an additional year and a half or so without doing any serious damage to the college."

In total, Klaich said the higher education system is requesting around $8.65 million in transitional money for Great Basin College, Western Nevada college, the Desert Research Institute and Boyd School of Law at UNLV.

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Education officials ask lawmakers to increase medical school funding past governor's proposal

Scholarship fund created to keep medical students in WNY

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Hoping to offset physician shortages in certain specialties, a group of doctors here has created a scholarship to encourage medical school students to stay in Western New York after they graduate.

The Western New York Medical Scholarship Fund recently awarded its first three recipients a minimum of $30,000 each annually for four years of education at the University at Buffalo School of Medicine and Biomedical Sciences.

The award winners must demonstrate financial need, graduate from a high school in one of the eight counties of Western New York, attend UB medical school and agree to practice in the region for an unspecified number of years.

The first three recipients are James Miller, a graduate of Frontier High School; Gina Sparacino, a Kenmore East High School graduate; and Alyssa Volmrich, a graduate of Holy Angels Academy.

Our goal is to keep more locally trained doctors in Western New York, Dr. John J. Bodkin II, co-chairman and founder of the fund, said in a statement.

Bodkin, a family physician at Highgate Medical Group, said similar programs in other cities have been successful.

We felt that if we could offer scholarships to Western New York students who went to high school here and have established family ties here, and then offer incentives, such as mentoring by local doctors, we could influence them to stay and practice here after graduation and residency, he said.

The funds goal is to raise enough money to sustain six to 10 scholarships a year over the next decade.

Organizations that have contributed a full scholarship include the Catholic Health System, Erie County Medical Center, HealthNow New York, Independent Health, Kaleida Health, Roswell Park Cancer Institute, and West-Herr Automotive Group, as well as the UB medical school and the UB Medical Alumni Association.

Contributors to the funds endowment include Amherst Ear Nose and Throat, Great Lakes Medical Imaging, Highgate Medical Group, Nephrology Associates of WNY, Northtowns Cardiology, Dr. Gerald Sufrin, WNY Urology Associates, Windsong Radiology Group and David M. Zebro, a principal of Strategic Investments & Holdings.

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Scholarship fund created to keep medical students in WNY

Sequencing the hookworm

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Ancylostoma ceylanicum genome provides researchers potential new drug and vaccine targets

WORCESTER, MA - In an advance that may potentially lead to new treatments for parasitic hookworms, scientists at the University of Massachusetts Medical School and Cornell University have sequenced the genome of the hookworm, Ancylostoma ceylanicum. The genome of the nematode that, according to some estimates, infects as many as 400 million people worldwide will help researchers find genes active during infection and devise new drugs or vaccines that target these genes. The study, which also includes researchers from the University of California San Diego and the California Institute of Technology, was published in Nature Genetics.

A debilitating tropical disease second only to malaria, hookworms are a leading cause of maternal and childhood morbidity in developing countries. They can live in the small intestine for as long as 10 years, drinking blood, robbing their hosts of iron and protein, interfering with absorption of critical nutrients and suppressing the immune system. Infection can lead to chronic anemia, as well as permanently stunt physical and intellectual development in infected children.

"The health burdens associated with soil-transmitted hookworms, especially in developing countries in Africa and the tropics are enormous," said Raffi V. Aroian, PhD, professor of molecular medicine at UMass Medical School and co-author of the study. "The only drugs we have to combat these parasites were developed to treat farm animals and are only partially effective. There is a tremendous need for a treatment for hookworms in humans that is safe, effective and affordable in the world's poorest countries."

Three species of hookworms can infect humans. People most commonly infected typically reside in poverty stricken areas with poor sanitation and are exposed to the worm through contaminated soil or food. Common in the American south 100 years ago, hookworms were virtually eradicated in the United States through improvements in sanitation and public health efforts during the early part of the 20th century.

Contemporary efforts to study the parasitic nematode have been hampered because the most common species, Necator americanus and Ancylostoma duodenale, cannot survive outside of a human host. This makes it difficult for researchers to study them in the lab and almost impossible to test new drugs and vaccines. It is why current treatments rely on drugs developed to treat similar worms in farm animals.

Though less common, because A. ceylanicum can infect and thrive in animals other than humans, such as rodents, it is an excellent experimental model for hookworm disease that allows scientists to study it in the laboratory. It also opens up the possibility that new drugs or vaccines for human hookworms can be designed and tested using A. ceylanicum.

"For this to happen, we first have to know as much as possible about A. ceylanicum's genes and the proteins they make," said Erich M. Schwarz, PhD, senior research associate at Cornell University and co-author of the study. "Until recently this would have been a very expensive and difficult undertaking, but next-generation technologies for analyzing DNA have made it possible for a small number of scientists to sequence and characterize the entire genome of an animal."

Isolating and sequencing DNA and RNA from hookworms during different stages of infection led to several significant findings. The A. ceylanicum genome constrains 313 million nucleotides, with 30,738 genes that encode for proteins and show gene activity. Researchers were also able to identify specific genes involved in infection. Among the genes identified were three large families of previously unknown proteins that are strongly synthesized during three different steps of infection. They also found more than 70 genes that likely encode for proteins which the worms need to survive but which are absent from mammals, making them possible drug targets. Finally, they found five genes that are extremely active in adult worms and are promising targets for vaccination because they are likely needed for feeding.

"The sequencing of A. ceylanicum adds to a growing number of genomes for parasitic nematodes that collectively infect over a billion people worldwide," said Dr. Aroian. "These genomes are crucial for inventing new drugs and vaccines against parasitic nematodes that rapidly evolve drug resistance and plague large populations in developing countries. With these new genomes we can begin rationally designing and testing treatments in the laboratory that can potentially benefit millions of people."

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Sequencing the hookworm

Funding approved for USF medical school in downtown Tampa

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TAMPA (FOX 13) -

The vacant one-acre site at the corner of Channelside Drive and Meridian Avenue in downtown Tampa is a step closer to becoming the new USF Medical School.

Thursday, the Florida Board of Governors, which governs the state university system, approved a $153 million plan, funding construction of the new Morsani College of Medicine and USF Heart Institute.

It's very important to be co-located. It's the right academic move for USF to be next to TGH, said USF President Dr. Judy Genshaft. Most of the students live downtown, and go back and forth to the campus, so there will be no additional costs to students.

The new school would put medical students much closer to Tampa General Hospital, the primary teaching hospital for the medical school. The location is also blocks away from USF CAMLS, the University's 3-story, 90,000 square foot, state-of-the-art simulation lab.

For the bigger Tampa Bay region, this is a game changer, says Tampa Mayor Bob Buckhorn. To now know that we are the vast majority of the way there to moving that medical school downtown for us is probably the most significant event that has occurred in the urban core in the last 20 years."

Tampa Bay Lightning owner Jeff Vinik, who donated the parcel of land to USF, released this statement:

"We are thrilled with today's news from Tallahassee and as a 'partner' with the University of South Florida on the project, we thank the Florida Board of Governors for their unanimous vote today. We look forward to making the Morsani School of Medicine and the accompanying Heart Institute one of the major anchors in our development district. We envision and embrace the vibrancy that USF and its students, faculty and staff will bring to downtown Tampa. This marks a great step forward."

The plan now must be approved by the lawmakers and Governor Rick Scott.

Under the current proposal, the University needs $57 million for the school, and an additional $50 million for the Heart Institute. Private sources would fund $41 million of the project.

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Funding approved for USF medical school in downtown Tampa