June 29, 2017 by John Toon The DRILL device is connected to a mass spectrometer to sort charged droplets and improve desolvation of ionized biomolecules for analysis. The device requires no modification of the mass spectrometer, and can be accommodated within the standard work flow now used by researchers. Credit: Rob Felt, Georgia Tech

Adding the equivalent of a miniature tornado to the interface between electrospray ionization (ESI) and a mass spectrometer (MS) has allowed researchers to improve the sensitivity and detection capability of the widely-used ESI-MS analytical technique. Among the scientific fields that could benefit from the new technique are proteomics, metabolomics and lipidomics which serve biomedical and health applications ranging from biomarker detection and diagnostics to drug discovery and molecular medicine.

Known as Dry Ion Localization and Locomotion (DRILL), the new device creates a swirling flow that can separate electrospray droplets depending on their size. In this application, one of many potential uses for DRILL, the smaller droplets are directed to enter the mass spectrometer, while the larger ones which still contain solvent remain in the vortex flow until the solvent evaporates. Removing the solvent allows analysis of additional ions that may be lost in current techniques and reduces the chemical "noise" that inhibits selectivity of the mass spectrometer.

"A major challenge for detecting small quantities of biomolecules using mass spectrometry technology is that we can't see everything that is actually in the sample," said Matthew Torres, an assistant professor in Georgia Tech's School of Biological Sciences. "The DRILL device provides a new way to solve that problem by increasing the number of ions we can get into the mass spec instrument so we can productively detect them. The ions are there now, but not necessarily in a form that the mass spec can handle."

Developed by researchers at the Georgia Institute of Technology with support from North Carolina State University, DRILL can be added to existing electrospray ionization mass spectrometers without modifying them.

"The principle is to make the droplets rotate and use inertia to separate them out by size," explained Andrei Fedorov, a professor in Georgia Tech's Woodruff School of Mechanical Engineering. "We want the droplets to stay in the flow long enough to remove the solvent. In practice, smaller droplets remain in the center, where they are can be removed first for analysis, while the larger ones remain on the edge of the flow until they are dried."

The key idea of DRILL is based on Fedorov's 2007 invention "Confining/Focusing Vortex Flow Transmission Structure, Mass Spectrometry Systems, and Methods of Transmitting Particles, Droplets, and Ions." (US Patent No. 7,595,487). In the past three years, the DRILL device has been developed with support from the National Institute of General Medical Sciences of the National Institutes of Health, and its latest version was described June 14 in the American Chemical Society journal Analytical Chemistry.

In electrospray ionization (ESI), an electric potential is applied to a solution inside a capillary, producing a strong electric field at the spray capillary tip. That leads to the expulsion of an aerosol containing charged droplets that carry the molecules to be analyzed. The ejected droplets then break up into smaller droplets, creating a plume that expands spatially beyond the inlet intake capacity of the mass spectrometer, resulting in sample loss. The DRILL device provides an effective interface for collection and transmission of charged analytes from ionization sources, such as ESI, to detection devices, such as mass spectrometers, resulting in significantly improved detection capability.

As much as 80 to 90 percent of large biopolymers (proteins, peptides, and DNA) are currently lost to analysis using existing ESI-MS techniques, which have grown in importance to the life sciences community. Capturing all of the biopolymers could lead to new discoveries, said Torres, whose lab studies post-translational changes in proteins. By allowing analysis of large biomolecules, DRILL could facilitate top-down proteomics in which complete protein molecules could be studied without the need to enzymatically break them up into smaller pieces before MS analysis.

"This could allow us to see combinatorial modifications that exist on a single protein molecule," said Torres. "It's very important for us to understand how proteins communicate with one another, and DRILL may allow us to do that by more effectively removing the solvent from these types of samples."

The Georgia Tech researchers are using DRILL in their lab to interface between liquid chromatography and the ESI-MS instrument. Multiple electrodes and inlet/outlet ports enable precise control over the flow generation and guiding electric field inside the DRILL, so the device can be configured for a variety of uses, Fedorov noted. In a general sense, DRILL adds a new approach for manipulating the trajectory of charged droplets, which, when combined with hydrodynamic drag forces and electric field forces, provides a rich range of possible operational modes.

DRILL can improve the signal-to-noise ratio by a factor of 10 in the detection of angiotensin I, a peptide hormone, and boost the sensitivity for angiotensin II ten-fold to picomole levels. DRILL demonstrated improved signal strength up to 700-fold for eight of nine peptides included in a test extract of biological tissue.

DRILL could potentially allow the study of entire cell contents, analyzing thousands of different molecule types simultaneously. That could allow researchers to see how these molecules change over time to detect problems in chemical pathways and to determine why drugs work in some people and not others.

"This could be a huge advance for biologists and others who are interested in protein biochemistry and cell biology because it enhances the sensitivity of the analytical technical and overcomes a major hurdle in studying large biological molecules," Torres added. "We expect to be able to see things we haven't been able to see before."

The Georgia Tech researchers have been collaborating with David Muddiman, a professor in the Department of Chemistry at North Carolina State University, on developing DRILL and its analytical characterization using state-of-the-art mass spectrometry experiments. A unique contribution of the North Carolina State University researchers is in using a powerful statistical method called "design of experiments" to guide the multi-parameter optimization of the DRILL device, resulting in identification of a sweet spot for optimal operation.

Fedorov and Torres hope to expand use of the DRILL device beyond Georgia Tech laboratories and further enhance its design. Among the near-term improvements planned is the addition of internal heating to accelerate the removal of solvent. "We see many additional improvements that will allow DRILL to further enhance the ESI-MS process," said Fedorov. "We plan to continue evolving it as more labs start to use the device."

Explore further: Triboelectric nanogenerators boost mass spectrometry performance

More information: Peter A. Kottke et al. DRILL: An ESI-MS interface for improved sensitivity via inertial droplet sorting and electrohydrodynamic focusing in a swirling flow, Analytical Chemistry (2017). DOI: 10.1021/acs.analchem.7b01555

Triboelectric nanogenerators (TENG) convert mechanical energy harvested from the environment to electricity for powering small devices such as sensors or for recharging consumer electronics. Now, researchers have harnessed ...

The sequencing of the human genome was only the beginning of a much more complex task deciphering the secrets of cellular chemistry and the mechanisms of disease. While the genome serves as a blueprint to understanding ...

Researchers at North Carolina State University and the University of North Carolina at Chapel Hill have developed a new surgical tool that uses low-frequency intravascular ultrasound to break down blood clots that cause deep ...

By simulating the removal of chips during the drilling of deep holes in metals and metal alloys, A*STAR researchers have paved the way for gun drills that are more durable, reliable, and have longer lifespans.

The world's smallest reaction chamber, with a mixing volume measured in femtolitres (million billionths of a litre), can be used to study the kind of speedy, nanoscale biochemical reactions that take place inside individual ...

Devices created by MEPhI scientists based on the principles of drift ion mobility spectrometry and mass spectrometry allow the quick analysis of the contents of complex multicomponent samples, which has multiple applications ...

A novel composite material has been developed by scientists in the Energy Safety Research Institute (ESRI) at Swansea University which shows promise as a catalyst for the degradation of environmentally-harmful synthetic dye ...

Taking inspiration from an unusual source, a Sandia National Laboratories team has dramatically improved the science of scintillatorsobjects that detect nuclear threats. According to the team, using organic glass scintillators ...

Scientists from Trinity College Dublin and AMBER, the Science Foundation Ireland-funded materials science research centre hosted in Trinity College Dublin, have created 'molecular cages' that can maximise the efficiency of ...

A pioneering X-ray technique that can analyse artefacts of any shape or texture in a non-destructive way has been developed by an international team of researchers led by the University of Leicester.

Adding the equivalent of a miniature tornado to the interface between electrospray ionization (ESI) and a mass spectrometer (MS) has allowed researchers to improve the sensitivity and detection capability of the widely-used ...

MIT researchers have identified the proper temperature and chemical mixture to selectively separate pure copper and other metallic trace elements from sulfur-based minerals using molten electrolysis. This one-step, environmentally ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Continue reading here:

Tiny 'tornado' boosts performance of electrospray ionization mass ... - Phys.Org

DUBLIN--(BUSINESS WIRE)--Alkermes plc (NASDAQ: ALKS) today announced positive preliminary topline results from ENLIGHTEN-1, the first of two key phase 3 studies in the ENLIGHTEN clinical development program for ALKS 3831, an investigational, novel, once-daily, oral atypical antipsychotic drug candidate for the treatment of schizophrenia. ENLIGHTEN-1 was a multinational, double-blind, randomized, phase 3 study that evaluated the antipsychotic efficacy, safety and tolerability of ALKS 3831 compared to placebo over four weeks in 403 patients experiencing an acute exacerbation of schizophrenia. The study also included a comparator arm of olanzapine, an established atypical antipsychotic agent with proven efficacy. The study met the prespecified primary endpoint, with ALKS 3831 demonstrating statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) scores compared to placebo (p<0.001). Data from the study also showed that olanzapine achieved similar improvements from baseline PANSS scores, compared to placebo (p=0.004). The study also met its key secondary endpoint of improvement on the Clinical Global Impression Severity (CGI-S) scale for ALKS 3831 versus placebo (p=0.002). ALKS 3831 is designed to provide the strong antipsychotic efficacy of olanzapine and a differentiated safety profile with favorable weight and metabolic properties.

The positive results of ENLIGHTEN-1 provide clear evidence of the safety, tolerability and antipsychotic efficacy of ALKS 3831 in a large, randomized registration trial, said Elliot Ehrich, M.D., Executive Vice President of Research and Development at Alkermes. The results of this phase 3 study also provide additional evidence of the antipsychotic properties of ALKS 3831 relative to olanzapine, an agent well known to clinicians. We look forward to completing our analysis of this large study and presenting the data at a future medical meeting.

Many physicians recognize the powerful efficacy profile of olanzapine, but are hesitant to prescribe it given the severe weight gain and metabolic side effects commonly associated with its use, said Christoph Correll, M.D., Professor of Psychiatry and Molecular Medicine at Hofstra Northwell School of Medicine. A new antipsychotic with robust efficacy and a favorable weight and metabolic profile compared to olanzapine would be a welcome addition to the schizophrenia treatment landscape. This study confirms a key element of this profile, with a clear demonstration of efficacy in a large, well-conducted clinical trial.

Overall, 91% of patients who received ALKS 3831 completed the study, compared to 89% of patients who received olanzapine and 83% of patients who received placebo. The most common adverse events for both the ALKS 3831 and olanzapine treatment groups were weight gain, somnolence and dry mouth.

Alkermes will present comprehensive data from the ENLIGHTEN-1 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal. ENLIGHTEN-2, a six-month phase 3 study evaluating the weight gain profile of olanzapine compared to ALKS 3831, is ongoing with data expected in 2018.

About the ENLIGHTEN-1 Study ENLIGHTEN-1 was a multinational, double-blind, randomized, phase 3 study that evaluated the antipsychotic efficacy, safety and tolerability of ALKS 3831 compared to placebo over four weeks in patients experiencing an acute exacerbation of schizophrenia. The study also included a comparator arm of olanzapine, an established atypical antipsychotic agent with proven efficacy but also metabolic liabilities, including significant weight gain.1 The trial included adult patients who met the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for schizophrenia, and had a PANSS score of 80 or higher at study baseline.

A total of 403 patients were randomized in a 1:1:1 manner to receive once-daily, oral tablets of ALKS 3831, olanzapine or placebo for four weeks. Patients randomized to the ALKS 3831 treatment group received a bilayer fixed-dose tablet of 10 mg samidorphan co-formulated with either 10 or 20 mg of olanzapine. Patients randomized to the olanzapine treatment group received either 10 or 20 mg of olanzapine. The primary efficacy endpoint of the study was the mean change from baseline at Week 4 in PANSS total score for ALKS 3831 compared to placebo, using a Mixed Model with Repeated Measurements (MMRM) model. The key secondary endpoint of the study was change from baseline in the CGI-S score at Week 4.

All participants who completed the double-blind portion of the study were eligible to continue in an open-label, long-term safety study and receive ALKS 3831 for an additional 12 months. The objective of the extension phase of the study is to assess the long-term safety, tolerability and durability of effect of ALKS 3831.

Conference Call Alkermes will host a conference call today, June 29, 2017, at 4:30 p.m. ET (9:30 p.m. BST), to discuss these topline results. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988. The conference call will also be webcast on the Investors section of Alkermes website at http://www.alkermes.com. The webcast will be archived on the Investors section of the Alkermes website for at least 90 days.

About the ENLIGHTEN Clinical Development Program The ENLIGHTEN clinical development program for ALKS 3831 is comprised of two key studies: a study evaluating the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks and a study assessing weight gain with ALKS 3831 compared to olanzapine in patients with schizophrenia over six months. The program also includes supportive studies to evaluate the pharmacokinetic and metabolic profile of ALKS 3831, the effect on body weight of ALKS 3831 in young adult patients early in their illness, and long-term safety.

About ALKS 3831 ALKS 3831 is a proprietary, investigational medicine designed as a broad-spectrum antipsychotic for the treatment of schizophrenia. ALKS 3831 is composed of samidorphan, a novel, new molecular entity co-formulated with the established antipsychotic agent, olanzapine, in a single bilayer tablet.

Weight gain is a common and clinically relevant metabolic side effect of atypical antipsychotic medications, and olanzapine, commercially available as ZYPREXA, has one of the highest incidences and greatest amounts of weight gain among the widely prescribed products in this class of drugs.1 ALKS 3831 is designed to provide the strong antipsychotic efficacy of olanzapine and a differentiated safety profile with favorable weight and metabolic properties.

About Schizophrenia Schizophrenia is a chronic, severe and disabling brain disorder. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions and social withdrawal), as well as by disorganized thinking. An estimated 2.4 million American adults have schizophrenia,2 with men and women affected equally.

About Alkermes Alkermes plcis a fully integrated, global biopharmaceutical company developing innovative medicines for the treatment of central nervous system (CNS) diseases. The company has a diversified commercial product portfolio and a substantial clinical pipeline of product candidates for chronic diseases that include schizophrenia, depression, addiction and multiple sclerosis. Headquartered in Dublin, Ireland, Alkermes plc has an R&D center in Waltham, Massachusetts; a research and manufacturing facility in Athlone, Ireland; and a manufacturing facility in Wilmington, Ohio. For more information, please visit Alkermes website atwww.alkermes.com.

Note Regarding Forward-Looking Statements Certain statements set forth in this press release constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the timing of receipt and reporting of the phase 1 metabolic and ENLIGHTEN-2 study results; and the therapeutic value, development plans and commercial potential of ALKS 3831. You are cautioned that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those expressed or implied in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: whether preclinical and clinical results for ALKS 3831 will be predictive of future clinical study results; whether the ENLIGHTEN-2 study for ALKS 3831 will be completed on time or at all; potential changes in cost, scope and duration of the ALKS 3831 clinical development program; whether ALKS 3831 could be shown ineffective or unsafe during clinical studies; and those risks and uncertainties described under the heading Risk Factors in the companys Annual Report on Form 10-K for the year ended Dec. 31, 2016 and Quarterly Report on Form 10-Q for the quarter ended Mar. 31, 2017 and in subsequent filings made by the company with the U.S. Securities and Exchange Commission (SEC), which are available on the SECs website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, the company disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release.

ZYPREXA is a registered trademark of Eli Lilly & Company.

1Komossa, K. et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews. 2010, Issue 3. Art. No.: CD006654.

2National Institutes of Health. Schizophrenia. Accessed on June 29, 2017 from http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=67&key=S#S.

Go here to read the rest:

Alkermes Announces Positive Preliminary Topline Results From Phase 3 Antipsychotic Efficacy Study of ALKS 3831 for ... - Business Wire (press release)

Georgia Tech News Center

Tiny Tornado Boosts Performance of Electrospray Ionization Mass Spectrometry Georgia Tech News Center Among the scientific fields that could benefit from the new technique are proteomics, metabolomics and lipidomics which serve biomedical and health applications ranging from biomarker detection and diagnostics to drug discovery and molecular medicine. and more »

View original post here:

Tiny Tornado Boosts Performance of Electrospray Ionization Mass Spectrometry - Georgia Tech News Center

Whole genome sequencing involves the analysis of all three billion pairs of letters in an individuals DNA and has been hailed as a technology that will usher in a new era of predicting and preventing disease.

However, the use of genome sequencing in healthy individuals is controversial because no one fully understands how many patients carry variants that put them at risk for rare genetic conditions and how theyand their doctorswill respond to learning about these risks.

In a new paper published June 26 in the Annals of Internal Medicine by investigators at Harvard Medical School and Brigham and Womens Hospital, along with collaborators at Baylor College of Medicine, report the results of the four-year, NIH-funded MedSeq Project, the first-ever randomized trial conducted to examine the impact of whole genome sequencing in healthy primary care patients.

In the MedSeq Project, 100 healthy individuals and their primary care physicians were enrolled and randomized so that half of the patients received whole genome sequencing and half did not.

Nearly 5,000 genes associated with rare genetic conditions were expertly analyzed in each sequenced patient, and co-investigators from many different disciplines, including clinical genetics, molecular genetics, primary care, ethicsand law, were involved in analyzing the results.

Researchers found that among the 50 healthy primary care patients who were randomized to receive genome sequencing, 11 (22 percent) carried genetic variants predicted to cause previously undiagnosed rare disease.

Two of these patients were then noted to have signs or symptoms of the underlying conditions, including one patient who had variants causing an eye disease called fundus albipunctatus, which impairs night vision.

This patient knew he had difficulty seeing in low-light conditions but had not considered the possibility that his visual problems had a genetic cause.

Another patient was found to have a genetic variant associated with variegate porphyria, which finally explained the patients and family members mysterious rashes and sun sensitivity.

The other nine participants had no evidence of the genetic diseases for which they were predicted to be at risk. For example, two patients had variants that have been associated with heart rhythm abnormalities, but their cardiology workups were normal. It is possible, but not at all certain, that they could develop heart problems in the future.

Sequencing healthy individuals will inevitably reveal new findings for that individual, only some of which will have actual health implications, said lead author Jason Vassy,an HMS assistant professor of medicine at Brigham and Womens and primary care physician at the VA Boston Healthcare System.

This study provides some reassuring evidence that primary care providers can be trained to manage their patients sequencing results appropriately, and that patients who receive their results are not likely to experience anxiety connected to those results. Continued research on the outcomes of sequencing will be needed before the routine use of genome sequencing in the primary care of generally healthy adults can be medically justified, Vassy said.

Primary care physicians received six hours of training at the beginning of the study regarding how to interpret a specially designed, one-page genome testing report summarizing the laboratory analysis.

Consultation with genetic specialists was available, but not required. Primary care physicians then used their own judgment about what to do with the information, and researchers monitored the interactions for safety and tracked medical, behavioral and economic outcomes.

The researchers noted that they analyzed variants from nearly 5,000 genes associated with rare genetic diseases. These included single genes causing a significantly higher risk for rare disorders than the low-risk variants for common disorders reported by direct-to-consumer genetic testing companies. No prior study has ever examined healthy individuals for pathogenic (high-risk) variants in so many rare disease genes.

We were surprised to see how many ostensibly healthy individuals are carrying a risk variant for a rare genetic disease, said Heidi Rehm, HMS associate professor of pathology at Brigham and Women's anddirector of the Laboratory for Molecular Medicine at Brigham and Women's.

We found that about one-fifth of this sample population carried pathogenic variants, and this suggests that the potential burden of rare disease risk throughout our general population could be far higher than previously suspected,said Rehm, a co-investigator on the study who directed the genome analysis.However, the penetrance, or likelihood that persons carrying one of these variants will eventually develop the disease, is not fully known.

Additionally, investigators compared the two arms of the studyand found that patients who received genome sequencing results did not show higher levels of anxiety. They did, however, undergo a greater number of medical tests and incurred an average of $350 more in health care expenses in the six months following disclosure of their results. The economic differences were not statistically significant with the small sample size in this study.

Because participants in the MedSeq Project were randomized, we could carefully examine levels of anxiety or distress in those who received genetic risk information and compare it to those who did not, said Amy McGuire,director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine.

While many patients chose not to participate in the study out of concerns about what they might learn, or with fears of future insurance discrimination, those who did participate evinced no increase in distress, even when they learned they were carrying risk variants for untreatable conditions, saidMcGuire, who supervised the ethical and legal components of the MedSeq Project.

There has also been great concern in the medical community about whether primary care physicians can appropriately manage these complicated findings. But when a panel of expert geneticists reviewed how well the primary care physicians managed the patients with possible genetic risk variants, the experts determined that only two of the 11 cases were managed inappropriately and that no harm had come to these patients.

MedSeq Project investigators note that the studys findings should be interpreted with caution because of the small sample size and because the study was conducted at an academic medical center where neither the patients nor the primary care physicians are representative of the general population. They also stressed that carrying a genetic risk marker does not mean that patients have or will definitely get the disease in question. Critical questions remain about whether discovering such risk markers in healthy individuals will actually provide health benefits, or will generate unnecessary testing and subsequent procedures that could do more harm than good.

Integrating genome sequencing and other -omics technologies into the day-to-day practice of medicine is an extraordinarily exciting prospect with the potential to anticipate and prevent diseases throughout an individuals lifetime, said senior author Robert C. Green, HMSprofessor of medicineat Brigham and Womens Hospital,associate member of the Broad Institute of Harvard and MITandleader ofthe MedSeq Project. But we will need additionalrigorously designed and well-controlled outcomes studies like the MedSeq Project with larger sample sizes and with outcomes collected over longer periods of time to demonstrate the full potential of genomic medicine.

The MedSeq Project is one of the sites in the Clinical Sequencing Exploratory Research Consortium and was funded by the National Human Genome Research Institute, part of the National Institutes of Health.

The Genomes2People Research Program at Brigham and Womens Hospital, the Broad Institute and Harvard Medical School conducts empirical research in translational genomics and health outcomes. NIH-funded research within G2P seeks to understand the medical, behavioral and economic impact of using genetic risk information to inform future standards. The REVEAL Study has conducted several randomized clinical trials examining the impact of disclosing genetic risk for a frightening disease. The Impact of Personal Genomics (PGen) Study examined the impact of direct-to-consumer genetic testing on over 1,000 consumers of two different companies. The MedSeq Project has conducted the first randomized clinical trial to measure the impact of whole genome sequencing on the practice of medicine. The BabySeq Project is recruiting families of both healthy and sick newborns into a randomized clinical trial where half will have their babys genome sequenced. Green directs the Program.

See original here:

Genetic Testing for the Healthy - Bioscience Technology

Image from PBC Website

Pasadena Bio Collaborative Incubator (PBC), high tech incubator for early stage start-ups and a regional workforce development magnet for scientists seeking wet lab R&D competency, announced the resignation from the Board of Directors of William Opel, MBA and PhD. The resignation is effective as of June 30.

Bill has been a board member since PBC first began operations in 2004 and his many contributions have been a significant factor in our growth, said PBC Chairman and former Pasadena mayor Bill Bogaard. We are truly grateful for his years of dedicated service and his wise counsel to the board and to management.

Dr. Opel was the President and CEO of Huntington Medical Research Institutes (HMRI) for nearly 40 years. He formed HMRI in the early 1980s, combining three research groups affiliated with Huntington Memorial Hospital, a tertiary medical center and teaching hospital. At that time, he launched one of the countrys first clinical magnetic resonance programs, which went on to gain acclaim in imaging applications development and in clinical spectroscopy.

His leadership at HMRI led to many advances in the field of medicine, including neural engineering, brain mapping, molecular medicine and clinical research. He worked with Huntington Hospital to encourage research projects by both medicine and surgery residents, as well as attending staff, and to expand HMRIs joint postdoctoral fellowship programs with Caltech. Dr Opel is active in community organizations and is past president of the PCC Foundation.

Background on PBC:

PBC was established in 2004 by the City of Pasadena, Pasadena City College, and California State University Los Angeles to work collaboratively with Pasadenas higher education institutions, entrepreneurs, investors and other stakeholders to provide high tech workforce development and incubate early stage bioscience start-ups. More information is available at http://pasadenabio.org/

See original here:

Pasadena Bio Collaborative Incubator Announces Board Change - Pasadena Now

Published: June 28, 2017 3:00 AM

Cleveland Clinic researchers have shown, for the first time in humans, that choline is directly linked to increased production of a gut bacteria byproduct that increases the risk of blood-clotting events like heart attack and stroke. However, the research also showed that adding a low dose of aspirin may reduce that risk.

In a small interventional study, the researchers provided oral choline supplements to groups of healthy vegans/vegetarians (eight patients) and omnivores (10 patients). Both groups showed at least a 10-fold increase in plasma levels of trimethylamine N-oxide (TMAO) a metabolite generated by gut microbes after choline supplementation, as well as an increase in platelet responsiveness, a risk factor for thrombotic events (blood clotting) like heart attack and stroke.

In a separate study, omnivores not taking supplements initially had platelet function tested at baseline, and then after taking a daily regimen of low-dose aspirin for at least a month. They then were followed for another two months while continuing to take aspirin and a daily supplement of choline. The researchers found that while elevated TMAO levels and enhanced susceptibility for platelet activation still occurred, the TMAO levels were attenuated by aspirin. These new findings suggest two things that a low dose of aspirin may partially counter the pro-thrombotic effects of a high TMAO plasma level associated with a Western diet rich in choline, commonly found in egg yolk and meats; and that a high TMAO level can partially overcome the beneficial anti-platelet effects of taking low dose aspirin.

The research team was led by Stanley Hazen, M.D., Ph.D., chair of the Department of Cellular & Molecular Medicine for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and Dr Wilson Tang, cardiologist and transplant specialist at the Miller Family Heart and Vascular Institute at Cleveland Clinic. The research will be published April 24 in Circulation, the American Heart Association's journal, with Weifei Zhu, Ph.D., of Dr. Hazen's laboratory as lead author.

"This is the first study in humans to directly demonstrate that dietary choline substantially elevates TMAO production by gut bacteria, impacting platelet function. It provides direct evidence of a mechanistic link between TMAO levels and risk for blood clotting events like heart attack and stroke, the major culprit for the development of cardiovascular events," Dr. Hazen said. "Further research is necessary to confirm these findings, but these studies suggest patients without known cardiovascular disease but with elevated TMAO levels may benefit from aspirin and diet modification in preventing blood clotting, which can lead to heart attack and stroke. They also suggest that a high TMAO level in a patient with known cardiovascular disease should be considered for more aggressive anti-platelet therapy."

Dr. Hazen, who also holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis, has previously linked TMAO to an increased risk of cardiovascular disease and has shown it can be a powerful tool for predicting future heart attacks, stroke and death in multiple patient populations.

TMAO is a byproduct of bacterial digestion of choline, lecithin and carnitine, nutrients that are especially abundant in animal products such as red meat, processed meats and liver. In 2016, his team discovered in animal models that gut microbes alter platelet function and thrombosis risks, and that microbial transplantation studies could be used to demonstrate the TMAO pathway plays a role in thrombosis potential in a stroke model in mice. Findings from this new study shows that dietary choline in humans raises TMAO levels, which may directly alter platelet function, increasing thrombosis (blood clot) potential. These studies help explain the strong association between plasma TMAO levels and heart attack and stroke risk observed in a study of over 4000 patients.

Continued here:

Cleveland Clinic research links gut bacteria, heart disease - The-review

In the United States, the annual incidence of bladder cancer is approximately70,000new cases, with a mortality rate of approximately 15,000/year. The most common subtype(70%) of bladder cancer is superficial, namely hte non-muscle invasive disease form limited to the urothelium. The rate of progression and recurrence is up to40 and70%, respectively. Urothelial cell carcinoma of the bladder is typically treated with transurethral resection. The cancerous cells can float onto the adjacent epithelium, increasing the risk of recurrence. The standard of care is to offer adjuvant intravesical agents to reduce the risk of progression and recurrence. Current intravesical treatments are costly and are associated with special biohazard handling protocols. Patients are treated with intravesical therapy with bacillus CalmetterGuerin(BCG) bacterium, or mitomycinC(MMC) following resection, both of which can cause moderate to severe side-effects which are rarely life-threatening. We previously examined the efficacy of epigallocatechin-3-gallate(EGCG) in comparison with MMC to prevent tumor cell implantation/growth in an animal model of superficial bladder cancer. Experiments revile that EGCG is slightly more effective than MMC at decreasing tumor cell implantation and consequent cancer growth in a bladder. This treatment requires the stringent sterile requirement of EGCG. EGCG can be unstable when sterilized at high temperatures. Thus, we evaluated two low temperature sterilization methods, such as ionizing radiation or the filtration method followed by freeze-drying. Both methods ensure the sterility of the sample; however, infrared and HPLC analysis revealed a slightly better stability of irradiated EGCG over the filtration method. The concentration of stable free radicals following irradiation was low, which are unlikely to exert any damaging effects to EGCG. Therefore, we consider that radiation will be the preferred method of EGCG sterilization, and that this may prove useful for the effective use of EGCG in the treatment of bladder cancer.

International journal of molecular medicine. 2017 Jun 14 [Epub ahead of print]

Katarzyna Dettlaff, Maciej Stawny, Magdalena Ogrodowczyk, Anna Jeliska, Waldemar Bednarski, Dorota Wtrbska-wietlikowska, Rick W Keck, Omar A Khan, Ibrahim H Mostafa, Jerzy Jankun

Department of Pharmaceutical Chemistry, Pozna University of Medical Sciences, 60780 Pozna, Poland., Institute of Molecular Physics, Polish Academy of Sciences, 60-179 Pozna, Poland., Department of Pharmaceutical Technology, Medical University of Gdask, 80-416 Gdask, Poland., Urology Research Center, Department of Urology, College of Medicine, University of Toledo, Toledo, OH 43614, USA.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28627636

Read this article:

Formulation and characterization of EGCG for the treatment of superficial bladder cancer. - UroToday

Whole genome sequencing involves the analysis of all three billion pairs of letters in an individuals DNA and has been hailed as a technology that will usher in a new era of predicting and preventing disease. However, the use of genome sequencing in healthy individuals is controversial because no one fully understands how many patients carry variants that put them at risk for rare genetic conditions and how they, and their doctors, will respond to learning about these risks.

In a new paper published June 26 in the Annals of Internal Medicine by investigators at Brigham and Womens Hospital and Harvard Medical School, along with collaborators at Baylor College of Medicine, report the results of the 4 year, NIH-funded MedSeq Project, the first-ever randomized trial conducted to examine the impact of whole genome sequencing in healthy primary care patients.

In the MedSeq Project, 100 healthy individuals and their primary care physicians were enrolled and randomized so that half of the patients received whole genome sequencing and half did not. Nearly 5000 genes associated with rare genetic conditions were expertly analyzed in each sequenced patient, and co-investigators from many different disciplines including clinical genetics, molecular genetics, primary care, ethics, and law were involved in analyzing the results.

Researchers found that among the 50 healthy primary care patients who were randomized to receive genome sequencing, 11 (22 percent) carried genetic variants predicted to cause previously undiagnosed rare disease. Two of these patients were then noted to have signs or symptoms of the underlying conditions, including one patient who had variants causing an eye disease called fundus albipunctatus, which impairs night vision. This patient knew he had difficulty seeing in low light conditions but had not considered the possibility that his visual problems had a genetic cause.

Another patient was found to have a genetic variant associated with variegate porphyria, which finally explained the patients and family members mysterious rashes and sun sensitivity. The other nine participants had no evidence of the genetic diseases for which they were predicted to be at risk. For example, two patients had variants that have been associated with heart rhythm abnormalities, but their cardiology work-ups were normal. It is possible, but not at all certain, that they could develop heart problems in the future.

Sequencing healthy individuals will inevitably reveal new findings for that individual, only some of which will have actual health implications, said lead author Jason Vassy, MD, MPH, a clinician investigator at Brigham and Womens Hospital, primary care physician at the VA Boston Healthcare System and assistant professor at Harvard Medical School. This study provides some reassuring evidence that primary care providers can be trained to manage their patients sequencing results appropriately, and that patients who receive their results are not likely to experience anxiety connected to those results. Continued research on the outcomes of sequencing will be needed before the routine use of genome sequencing in the primary care of generally healthy adults can be medically justified.

Primary care physicians received six hours of training at the beginning of the study regarding how to interpret a specially designed, one-page genome testing report summarizing the laboratory analysis. Consultation with genetic specialists was available, but not required. Primary care physicians then used their own judgment about what to do with the information and researchers monitored the interactions for safety and tracked medical, behavioral and economic outcomes.

Researchers note that they analyzed variants from nearly 5000 genes associated with rare genetic diseases. These included single genes causing a significantly higher risk for rare disorders than the low risk variants for common disorders reported by direct-to-consumer genetic testing companies. No prior study has ever examined healthy individuals for pathogenic (high risk) variants in so many rare disease genes.

We were surprised to see how many ostensibly healthy individuals are carrying a risk variant for a rare genetic disease, said Heidi Rehm, PhD, director of the Laboratory for Molecular Medicine and a co-investigator on the study who directed the genome analysis. We found that about one-fifth of this sample population carried pathogenic variants, and this suggests that the potential burden of rare disease risk throughout our general population could be far higher than previously suspected.

However, the penetrance, or likelihood that persons carrying one of these variants will eventually develop the disease, is not fully known.

Additionally, investigators compared the two arms of the study, and found that patients who received genome sequencing results did not show higher levels of anxiety. They did, however, undergo a greater number of medical tests and incurred an average of $350 more in health care expenses in the six months following disclosure of their results. The economic differences were not statistically significant with the small sample size in this study.

Because participants in the MedSeq Project were randomized, we could carefully examine levels of anxiety or distress in those who received genetic risk information and compare it to those who did not. While many patients chose not to participate in the study out of concerns about what they might learn, or with fears of future insurance discrimination, those who did participate evinced no increase in distress, even when they learned they were carrying risk variants for untreatable conditions, said Amy McGuire, PhD, director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine. McGuire supervised the ethical and legal components of the MedSeq Project.

There has also been great concern in the medical community about whether primary care physicians can appropriately manage these complicated findings. But when a panel of expert geneticists reviewed how well the primary care physicians managed the patients with possible genetic risk variants, the experts determined that only two of the 11 cases were managed inappropriately and that no harm had come to these patients.

MedSeq Project investigators note that the studys findings should be interpreted with caution because of the small sample size and because the study was conducted at an academic medical center where neither the patients nor the primary care physicians are representative of the general population. They also stressed that carrying a genetic risk marker does not mean that patients have or will definitely get the disease in question. Critical questions remain about whether discovering such risk markers in healthy individuals will actually provide health benefits, or will generate unnecessary testing and subsequent procedures that could do more harm than good.

Integrating genome sequencing and other omics technologies into the day-to-day practice of medicine is an extraordinarily exciting prospect with the potential to anticipate and prevent diseases throughout an individuals lifetime, said senior author Robert C. Green, MD, MPH, medical geneticist at Brigham and Womens Hospital, an associate member of the Broad Institute, and professor of medicine at Harvard Medical School who leads the MedSeq Project. But we will need additional rigorously designed and well-controlled outcomes studies like the MedSeq Project with larger sample sizes and with outcomes collected over longer periods of time to demonstrate the full potential of genomic medicine.

The MedSeq Project is one of the sites in the Clinical Sequencing Exploratory Research Consortium and was funded by the National Human Genome Research Institute, part of the National Institutes of Health.

The Genomes2People Research Program at Brigham and Womens Hospital, the Broad Institute and Harvard Medical School conducts empirical research in translational genomics and health outcomes. NIH funded research within G2P seeks to understand the medical, behavioral and economic impact of using genetic risk information to inform future standards. The REVEAL Study has conducted several randomized clinical trials examining the impact of disclosing genetic risk for a frightening disease. The Impact of Personal Genomics (PGen) Study examined the impact of direct-to-consumer genetic testing on over 1000 consumers of two different companies. The MedSeq Project has conducted the first randomized clinical trial to measure the impact of whole genome sequencing on the practice of medicine. The BabySeq Project is recruiting families of both healthy and sick newborns into a randomized clinical trial where half will have their babys genome sequenced. Robert C. Green, MD, MPH directs the Program.

Read the original:

Genetic Testing for The Healthy - Harvard Medical School (registration)

There is new evidence that a compound found in cruciferous vegetables like broccoli and cabbage may enhance the anticancer benefits of the platinum-based drug cisplatin in the treatment of pleural mesothelioma.

Although malignant mesothelioma is highly resistant to conventional cancer treatments, most mesothelioma patients will receive chemotherapy with cisplatin and pemetrexed (Alimta) as part of a multi-modal approach to treatment.

Now, researchers Yoon-Jin and Sang-Han Lee of Koreas Soonchunhyang University say the isothiocyanate compound sulforaphane could help cisplatin kill more mesothelioma cells with minimal side effects.

Cruciferous vegetables like broccoli, Brussels sprouts, cabbages, and cauliflower are rich in anti-cancer compounds. Sulforaphane is an organosulfur compound produced when the plant is damaged, such as from chewing.

To test its potential value in the treatment of mesothelioma, the research team exposed a sample of human pleural mesothelioma cells to a mixture of sulforaphane and cisplatin.

Combination treatment with the two compounds exhibited synergistic growthinhibiting and apoptosispromoting [cell death] activities, as demonstrated by a series of proapoptotic events, write the researchers in the journal Molecular Medicine Reports.

The study utilized a concentration of sulforaphane already shown to have limited toxicity in healthy cells.

The combination of sulforaphane and cisplatin triggered a cascade of reactions inside the treated mesothelioma cells. Reactive oxygen species, a byproduct of cellular stress, began to accumulate, the membranes around the energy-producing mitochondria became weak, and the nuclei of many cells became fragmented.

But cancer cells are tenacious and mesothelioma cells are no exception. One mechanism through which they protect themselves against cancer-fighting drugs is autophagy. During autophagy, certain cellular organelles degrade and are broken down so their components can be reused in new cancer cells.

When the researchers used another compound to artificially stifle autophagy, the mesothelioma-killing power of the sulforaphane/cisplatin treatment combination increased.

The results of the present study provide a rationale for targeting cytoprotective autophagy as a potential therapeutic strategy for malignant mesothelioma, concludes the report.

Although the study utilized a compound found in cruciferous vegetables, it does not suggest that consuming these vegetables will have the same effect. Mesothelioma patients should work closely with their doctor or dietary consultant to ensure that they are eating a diet that will best support their body through the stress of cancer treatment.

Source:

Lee, YJ and Lee, SH, Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells, June 15, 2017, Molecular Medicine Reports, Epub ahead of print

Read the original:

Compound in Broccoli May Enhance Mesothelioma Treatment with Cisplatin - Surviving Mesothelioma

news

Finnish researchers have found that an accumulation of gene mutations, similar to those typically seen in the development of cancer, also occur in some patients with rheumatoid arthritis.

Gene mutations that accumulate in somatic cells have a significant impact on the development of cancer, yet no studies on their involvement in the pathogenesis of autoimmune diseases have previously been conducted. A research project conducted in cooperation by the University of Helsinki and the Helsinki University Central Hospital found that somatic mutations were also present in patients with rheumatoid arthritis.

Published in the Nature Communications journal, the study found mutations in genes important to the immune defence system in white cells separated from blood samples taken from patients recently diagnosed with rheumatoid arthritis.

It may be possible that these mutations affect the regulation of the inflammatory process, says Satu Mustjoki, a research professor at the Finnish Cancer Institute and the University of Helsinki.

Altogether 85 patients with recently diagnosed rheumatoid arthritis participated in the study, in addition to which there were 20 healthy control subjects. By utilising the latest deep sequencing techniques, the researchers identified mutations in one fifth of the patients. All identified mutations were located in cells known as killer cells, or cytotoxic CD8+ T cells. No mutations were found in helper cells, or CD4+ T cells.

One somatic mutation was found in a single healthy control subject, which means that the finding is not entirely arthritis specific, notes Professor Marjatta Leirisalo-Repo, a specialist in rheumatology.

The ability found in T cells to recognise countless different protein structures inherent in, for example, pathogens, is based on their versatile selection of T cell receptors. This selection is formed in the thymus, where gene stubs that code the T cell receptors found in T cells are split and rearranged into functioning receptors. Thus, the surface of each new T cell is imbued with a unique T cell receptor.

When the immune defence system is activated, T cells multiply exponentially while identical T cells form cell clones that can be identified by the rearrangement of their shared, unique T cell receptor.

Enlarged T cell clones were found in all patients with rheumatoid arthritis concomitant with somatic mutations. Further investigation proved that the mutations were limited to these enlarged cell clones.

This indicates that mutations are formed only in mature T cells, not at the stem cell level, say BM Paula Savola and PhD Tiina Kelkka, the main authors of the article. If mutations were formed at the earlier differentiation stage, they would have been present in CD8+ T cells and CD4+ helper cells expressing other T cell receptor types as well.

The mutations were found to be permanent, since identical clones and mutations were found in the patients white blood cells several years after the original finding.

For now, there is no certainty on how these mutations affect the regulation of chronic inflammations. They may be, for lack of a better word, genomic scars formed as a result of the activation of the immune defence system, says Mustjoki.

In any case, this research project revealed a new connection on the molecular level between autoimmune diseases and cancer, which brings us one step closer to understanding these diseases.

The starting point for this project was earlier findings related to LGL leukaemia made by Mustjokis research group. In LGL leukaemia, somatic mutations often found in the STAT3 gene and located also in the cytotoxic T cells of patients cause a slowly progressing blood disorder, in addition to which they predispose patients to autoimmune diseases. The most common autoimmune disease related to LGL leukaemia is rheumatoid arthritis.

In the future, we intend to study the prevalence of this phenomenon in other inflammatory conditions and the practical significance of these mutations as regulators of inflammatory reactions, says Mustjoki.

Researchers from the Faculty of Medicine at the University of Helsinki, the Institute for Molecular Medicine Finland, the Blood Service and the Departments of Rheumatology and Hematology at the Helsinki University Hospital participated in the research project. The project was led by Professors Satu Mustjoki, Marjatta Leirisalo-Repo and Kimmo Porkka.

Funding for the project was provided, among others, by the Academy of Finland and the European Research Council.

Follow this link:

New gene mutations found in white blood cells in rheumatoid arthritis patients - Drug Target Review

June 26, 2017 Credit: CC0 Public Domain

Cancer tumours manipulate a natural cell process to promote their survival suggesting that controlling this mechanism could stop progress of the disease, according to new research led by the University of Oxford.

Non-sense mediated decay (NMD) is a natural physiological process that provides cells with the ability to detect DNA errors called nonsense mutations. It also enables these cells to eliminate the mutated message (decay) that comes from these faulty genes, before they can be translated into proteins that can cause disease formation. NMD is known among the medical community for the role it plays in the development of genetic diseases such as Cystic Fibrosis and some hereditary forms of cancers. But not all nonsense mutations can elicit NMD, so until now, it's wider impact on cancer was largely unknown.

Biomedical researchers and computer scientists from the University of Oxford Medical Sciences Division and the University of Birmingham developed a computer algorithm to mine DNA sequences from cancer to accurately predict whether or not an NMD would eliminate genes that had nonsense mutations. The work originally focused on ovarian cancers, and found that about a fifth of these cancers use NMD, to become stronger. This is because NMD ensures that the message from a gene called TP53, which ordinarily protects cells from developing cancer is almost completely eliminated. In the absence of NMD, a mutated TP53 might still retain some activity but NMD ensures that this is not the case.

Based on this research, the team predicts that because cancers essentially feed on NMD, they become dependent on it in some cases. If scientists were therefore able to inhibit or control the process, it is possible that they could also control cancer and prevent the progression of the disease.

Dr Ahmed Ahmed, Co-author and Professor of Gynaecology Oncology at the Nuffield Department of Obstetrics & Gynaecology and the head of the Ovarian Cancer Cell Laboratory, at the Weatherall Institute of Molecular Medicine at the University of Oxford, said: "Our first observations of evidence of the role of NMD in ovarian cancer were tantalizing. We found that NMD precisely explained why there was almost no expression of TP53 in certain ovarian cancers. We went on to test the role of NMD in other cancer types and the evidence of the role of NMD was compelling. This opens the door for exciting possibilities for customised treatments including individualized immunotherapies for patients in the future."

Following the ovarian cancer analysis, the team expanded the study to include other cancer types. They analysed about a million different cell mutations in more than 7,000 tumours from the Cancer Genome Atlas covering 24 types of cancer. The team was able to map how each cancer type used NMD revealing the remarkable extent to which NMD helps cancer to survive.

Katherine Taylor, CEO of Ovarian Cancer Action, who part-funded the research, said: "This is very exciting news. Professor Ahmed and his team have identified how cancer cells rely on a process called NMD for their survival. This discovery could help clinicians identify and inhibit the process, giving them much better control of a person's cancer.

"Ovarian cancer is a very complicated disease and survival rates are low, with only 46% of women living beyond five years after diagnosis. So understanding how we can prevent the disease from thriving is imperative if we are to improve the outcome for more women.

"It's fantastic to see how our funding is helping make real progress and we couldn't do this without the generosity of our supporters. We look forward to seeing where Professor Ahmed takes his research next."

Moving forward the team will focus on testing their theory and understanding to what degree stopping the NMD process allows them to control tumours.

Co-author, Dr Christopher Yau, a computational scientist at the Institute of Cancer and Genomic Sciences, University of Birmingham said: "As a result of these findings, we now plan to apply the same computer algorithm to determine if NMD affects cancer patients in The 100,000 Genomes Project. These investigations may pave the way to new treatment possibilities for NHS patients in the future."

Explore further: Two Oxford research discoveries offer hope for managing ovarian cancer

More information: The full paper citation is 'A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay,' and it will be published in Nature Communications on Monday 26 June 2017.

Oxford University researchers have found a way to detect ovarian cancer early and identified an enzyme that is key in making ovarian cancer more deadly. Their results, published in two journals, provide new research routes ...

Levels of circulating tumor DNA (ctDNA) detected in a blood test are correlated with the size of ovarian cancers and can predict a patient's response to treatment or time to disease progression, according to a retrospective ...

Testing for a gene commonly mutated in ovarian cancers could pick out patients who will respond well to a promising new class of cancer drugs, a major new study reveals.

A recent discovery by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) may lead to a new treatment strategy for an aggressive ovarian cancer subtype.

A new discovery that sheds light on the genetic make up of ovarian cancer cells could explain why some women survive longer than others with this deadly disease. A multi-disciplinary team led by the Research Institute of ...

Mutations in the BRCA1 gene are one of the most common risk factors for breast and ovarian cancers. Although tumors that harbor BRCA1 mutations initially respond well to cancer treatments, many tumors eventually become less ...

"Your cancer has metastasized. I'm sorry," is something no one wants to hear a doctor say.

Cancer tumours manipulate a natural cell process to promote their survival suggesting that controlling this mechanism could stop progress of the disease, according to new research led by the University of Oxford.

An international research team has found a way to improve the anti-cancer effect of a new medicine class called 'Smac mimetics'.

A subgroup of patients with osteosarcoma - a form of bone cancer - could be helped by an existing drug, suggest scientists from the Wellcome Trust Sanger Institute and their collaborators at University College London Cancer ...

Some patients with a form of advanced kidney cancer that carries a poor prognosis benefited from an experimental drug targeted to an abnormal genetic pathway causing cancerous growth, according to research led by a Dana-Farber ...

A team of researchers at McMaster University has identified a unique feature of cancer stem cells that can be exploited to kill the deadly cells thought to be the reason that cancer comes back after therapy. Understanding ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read the rest here:

Cancer hijacks natural cell process to survive - Medical Xpress - Medical Xpress

Graduate students deserve a place on campus.

by Nick Warren and Perry Scheetz | 6/23/17 2:15am

This spring saw significant discussion on the state of graduate and undergraduate education at Dartmouth. An opinion column published by The Dartmouth editorial board suggested that formation of the new School of Graduate and Advanced Studies engendered an alleged decline in the quality of undergraduate education and the satisfaction reported by the undergraduate community.In response, Graduate Student Council President Kyla Rodgers argued that graduate students improve undergraduate education by providing greater access to research opportunities and facilities, creating interdisciplinary spaces and being effective role models. This conversation continued among the graduate student population and was a primary discussion point at a lunch with President Hanlon and several graduate student leaders.President Hanlon assured the graduate student leaders that our community would not be exploited for the benefit of undergraduate education.

However, due to an unexpected overabundance of newly accepted undergraduates for the class of 2021, the only option for on-campus graduate student housing has been eliminated. Graduate students are again discussing the level of acceptance we have among the wider Dartmouth community. A petition was created and unanimously supported through a resolution by the Graduate Student Council for people to voice their support of on-campus graduate housing; The petition garnered 411 signatures.The administration failed to consult with the graduate student community about this move before making a decision, but has since explained their reasoning to graduate student leaders. The solution for the undergraduate housing crisis appears to benefit the undergraduate community at the expense of the graduate community. We recognize that this decision did not come from the undergraduate community and continue to support the growth and education of our undergraduates. We simply wish that graduate students be considered an equal part of the wider Dartmouth community, not just from an administrative standpoint, but also a cultural one.

In 2016, the graduate community welcomed 40 undergraduate students into North Park, again an overcrowding issue, to support the Colleges new housing initiative. Our community openly embraced the prospect of creating a stronger Dartmouth community and sacrificed 40 of our 110 housing spaces, with the assumption that construction for new undergraduate dorms would begin shortly. In a meeting with Provost Dever, she described early plans to build a new undergraduate dormitory, but the implementation is years away. The board of trustees recently authorized $200,000 in spending for feasibility and planning for new undergraduate housing, which will hopefully kick start this process. Further complicating the housing situation, there is an agreement between the City of Hanover and the College to allow no more than 10 percent of the undergraduate population to live off-campus. Lacking any easy and cost-effective alternatives, commandeering the remaining rooms in North Park was viewed as the most viable solution.

North Park was built in2004as a housing unit specifically for first year graduate students and has since become a cherished part of the graduate student community. North Park is so central to the graduate student community that many departments provide tours of the facilities during recruitment processes. North Park is especially important to international graduate students who do not have their own means of transportation and generally arrive to campus with only a suitcase. The advanced transit bus routes are nice for people without cars, but they do not run at night or on the weekends, when we often have to do research or go grocery shopping. Forcing first year graduate students off campus would greatly disadvantage incoming graduate students, especially students without cars or drivers licenses. Additionally, international students may be unfamiliar with leasing agreements in the U.S. and inexperienced with finding potential living spaces. Having a year of college-provided housing removes those hurdles to attend Dartmouth. Being in rural New Hampshire, we need policies and practices that actively promote diversity. Convenient housing options are key to attracting international students with unique and necessary perspectives. The College has said they are committed to increasing the diversity on campus through the inclusive excellence initiative.By sacrificing the ability to house graduate students in North Park, the College loses an enormous recruitment draw for bright minds from across the globe.

While the administration has promised to find housing for the graduate students who already signed leases for next year, they will not be living in a tight-knit on-campus community. Additionally, the extra 70 students who applied for the housing lottery were turned away without any compensation. Starting graduate school can be a very lonely experience, not just for international students. Living off-campus puts us at a distance from social and academic events organized by the Graduate Student Council, as well as undergraduate-focused organizations such as the Programming Board. This physical distance disincentivizes us to participate in campus activities. Since the buses do not run on the nights or weekends when these events are generally held, many graduate students are deterred from participating. This is arguably the single largest reason for why graduate students do not feel or are not perceived to be as connected to the Dartmouth community as its other members. In contrast, proximity breeds interaction. Living adjacent to the campus social life helps first year students integrate into Dartmouth culture. As was discussed at the lunch with President Hanlon, graduate student leaders are trying to form stronger connections between the graduate and undergraduate communities to enrich both of our experiences. The decision to remove our presence from campus housing exacerbates feelings of disconnection and encumbers integration efforts following the One Dartmouth initiative.

Leaders of the graduate student community understand that the administration must often make difficult decisions. However, removing graduate students from North Park appeared to be particularly detrimental to our community for the benefit of another. We have been reassured by Provost Dever that our input will be welcomed in future discussions about issues affecting the graduate community and that the College is committed to supporting graduate education. Committing to return on-campus graduate housing in the future would be a powerful message of support that the administration could give to the graduate community. In the meantime, the College should help make it as easy as possible for first year international students to find housing in Hanover and become a part of Dartmouth. We look forward to helping the effort to improve graduate and undergraduate education at Dartmouth. As President Hanlon told the graduate student leaders during lunch at his house in May, I see graduate and undergraduate education as co-beneficial. The Colleges policies and solutions to difficult problems should continue to reflect that sentiment.

Nicholas Warren is a PhD candidate in the Program in Experimental and Molecular Medicine. He also serves as a representative on the Graduate Student Council.

Dr. Perry Sheetz recently defended a PhD in Chemistry. She also has served on the Graduate Student Council Executive Board as the North Park Activities Coordinator for the past 3 years.

A shortened version of this article was published in print.

The Dartmouth welcomes guest column submissions. We request that guest columns be the original work of the submitter. Submissions and questions may be sent to either opinion@thedartmouth.com and editor@thedartmouth.com. Submissions will receive a response within three business days.

Correction Appended (June 24, 2017): This column was updated to correct a misspelling in an author's name.

Originally posted here:

Scheetz & Warren: We Are Dartmouth Too - The Dartmouth

CTVNews.ca Staff Published Saturday, June 24, 2017 10:00PM EDT Last Updated Saturday, June 24, 2017 10:01PM EDT

Not many Canadians have ever heard of "biofilms," but doctors and infectious diseases experts know them well. The slimy, glue-like sheets of bacteria or fungi can grow on tissues or wounds, forming a protective layer around themselves that make it difficult to kill the infections.

Now Canadian researchers say they may have found a way of fighting biofilms by breaking up their protective coatings.

Not all biofilms are dangerous; there is likely a biofilm of plaque on your teeth right now, if it's been a while since you last brushed.

But some biofilms are dangerous and can progress into serious infections, says Dr. Don Sheppard, the director of the division of Infectious Diseases at the McGill University Health Centre in Montreal.

"They can attach to skin and wounds. They can attach to prosthetic devices, like IV catheters, urinary catheters, the artificial hips that we put inside people. And they can adhere to those surfaces with a strength that exceeds that of crazy glue," he says.

Because biofilms work together to form a kind of armour around themselves, colonies of bacteria or fungi can easily fight off immune system attacks, and even high doses of antibiotics. That leaves doctors with little in their arsenal to fight them, says Lynne Howell, a senior scientist in in molecular medicine at SickKids Hospital in Toronto.

"The fact we don't have any way to prevent or treat them is a major problem," she said.

In fact, it's estimated that more than 70 per cent of hospital-acquired infections are associated with biofilms.

Scientists around the world have been struggling to design new weapons against biofilms. Now, Canadian researchers think they've found a way of breaking through a biofilm's protective coating, using enzymes.

Powell, who was part of the team working on the new approach, says the enzymes help to "bust up" a biofilm's shell, or matrix, creating holes that allow antibiotics or the immune system to kill the bacteria or fungi.

What's more, the enzyme technology can also prevent biofilms from forming at all.

"This is the first time we have taken a big step forward in getting a new therapy based on something that we didn't know existed five years ago," says Sheppard.

Sheppard and Howell's team conducted their research over four years, focusing on two of the most common organisms responsible for serious lung infections: a bacterium called Pseudomonas aeruginosa and a fungus called aspergillus fumigatus.

They discovered that enzymes called glycoside hydrolases could eat through all the sugar molecules that glue biofilms together.

Results of their research are available in Proceedings of the National Academy of Sciences.

Researchers are now beginning to test the enzymes in animals before beginning testing in patients.

With a report from CTV medical specialist Avis Favaro and producer Elizabeth St. Philip

Original post:

Canadian team helps find way to break through armour of dangerous biofilms - CTV News

MATTHEW PETROZELLI

Petrozelli, Valley National Financial Advisors executive vice president and chief operating officer, has been accepted into the Forbes Finance Council, an invitation-only community for executives in accounting, financial planning, wealth and asset management and investment firms.

Petrozelli joins other Forbes Finance Council members to become part of a curated network of successful peers and get access to a variety of exclusive benefits and resources, including the opportunity to submit thought leadership articles and short tips on industry-related topics for publishing on Forbes.com.

Forbes Councils combines an innovative, high-touch approach to community management perfected by the team behind Young Entrepreneur Council with the extensive resources and global reach of Forbes. As a result, Forbes Council members get access to the people, benefits and expertise they need to grow their businesses and a dedicated member concierge who acts as an extension of their own team, providing personalized one-on-one support.

DONALD M. BERNHARD and THE REV. BOB STEVENS

The Trustees of The Century Fund have appointed Bernhard and Stevens to succeed John Leh II and Grant E. Harrity as trustees.

Donald M. Bernhard is Eexecutive director of the Downtown Allentown Community Development Initiative, an initiative aimed at revitalizing Center City Allentown neighborhoods. He served as director of community affairs at PPL Corp. from 1996 to 2014. Prior to joining PPL, Bernhard served for 20 years as community development director of Allentown. Bernhard is a graduate of the University of Pittsburgh and received an master of arts degree political science/public administration from Brown University.

OLAF STARORYPINSPINSPKI/HEALTH NETWORK

The Rev. Bob Stevens has served as senior pastor of Zion's Liberty Bell United Church of Christ in Allentown since 1995. A nationally certified intentional interim pastor, Stevens served on the educational faculty of the Interim Ministry Network, Baltimore, and was a referral consultant for the Alban Institute, Washington, D.C. He is a master's graduate of Moravian Theological Seminary and Princeton Theological Seminary, and was an adjunct faculty instructor at both seminaries.

DR. JEFFREY WISOTZKEY

Wisotzkey has joined Health Network Laboratories as clinical laboratory director. Wisotzkey will continue to serve as HNL's Scientific Officer, a position he has held since 2015, leading HNL's diagnostics innovation portfolio in molecular precision medicine.

With more than 25 years of experience leading strategic, scientific and laboratory operations in various clinical settings, including the past two years as Scientific Officer at HNL, Wisotzkey is eager to lead HNL through a future filled with exciting opportunities.

Wisotzkey's vision for the future of testing at HNL originates from the company's longstanding dedication to improving outcomes for patients and reducing costs for healthcare systems. By using tests that are targeted to reveal a patient's individual profile, all the way down to the molecular and genetic levels, HNL's diagnostic testing provides actionable information to caregivers that leads to improved disease screening and prevention strategies, to more appropriate and timely treatments, which all leads to lower costs and better outcomes.

Wisotzkey received his doctoral degree from the University of Houston in molecular biology and completed his postdoctoral training at Pennsylvania State University's Hershey Medical Center. He is a board certified High Complexity Laboratory Director (HCLD), a Clinical Consultant (CC) and the creator and director of one of the first molecular labs in the nation to be established in a community-based teaching hospital The Molecular Diagnostics and Research Laboratory at York Hospital. He previously served as Clinical Laboratory Director at Genomind, and prior to that as Technical Director of Laboratory Operations at the Central Pennsylvania Alliance Laboratory.

Read more:

Matthew Petrozelli has been accepted into the Forbes Finance Council, and other hires and promotions - Allentown Morning Call

We demonstrate that glycoside hydrolases derived from the opportunistic fungusAspergillus fumigatusand Gram-negative bacteriumPseudomonas aeruginosacan be exploited to disrupt preformed fungal biofilms and reduce virulence, wrote the authors of the PNAS article. Additionally, these glycoside hydrolases can be used to potentiate antifungal drugs by increasing their hyphal penetration, to protect human cells from fungal-induced injury, and attenuate virulence ofA. fumigatusin a mouse model of invasive aspergillosis.

This work is the result of a four-year collaboration between a McGill scientists led by Don Sheppard, M.D., and SickKids scientists led by Lynne Howell, Ph.D. "Rather than trying to develop new individual 'bullets' that target single microbes, explained Dr. Sheppard, we are attacking the biofilm that protects those microbes by literally tearing down the walls to expose the microbes living behind them. It's a completely new and novel strategy to tackle this issue.

"We made these enzymes into a biofilm-destroying machine that we can use outside the microbe where the sugar molecules are found," added co-first study author Brendan Snarr, a Ph.D. student in Dr. Sheppard's laboratory. "These enzymes chew away all of the sugar molecules in their path and don't stop until the matrix is destroyed."

"Previous attempts to deal with biofilms have had only limited success, mostly in preventing biofilm formation. These enzymes are the first strategy that has ever been effective in eradicating mature biofilms, and that work in mouse models of infection," noted Dr. Sheppard.

"When we took the enzymes from bacteria and applied them to the fungi, we found that they worked in the same way on the fungi biofilm; which was surprising," commented Dr. Howell. "What's key is that this approach could be a universal way of being able to leverage the microbes' own systems for degrading biofilms. This has bigger implications across many microbes, diseases, and infections."

"Over 70% of hospital-acquired infections are actually associated with biofilms, and we simply lack tools to treat them," stated Dr. Sheppard. According to both lead scientists, the potential of this novel therapy is enormous and they hope to commercialize it in the coming years.

Original post:

Biofilm-Busting Enzymes May Rout Hospital-Acquired Infections - Genetic Engineering & Biotechnology News

Researchers have developed a way to use the same enzymes that help microbes create biofilms to keep biofilms from forming and even destroy them.

Biofilms are slimy, glue-like membranes that microbes, like bacteria and fungi, make in order to colonize surfaces. They can grow on animal and plant tissues, and even inside the human body on medical devices such as catheters, heart valves, or artificial hips.

Over 70 percent of hospital-acquired infections are actually associated with biofilms and we simply lack tools to treat them!

Biofilms protect microbes from the bodys immune system and increase their resistance to antibiotics. They represent one of the biggest threats to patients in hospital settings.

The teams research, which appears in the Proceedings of the National Academy of Sciences, creates a promising avenue for the development of innovative strategies to treat a wide variety of diseases and hospital-acquired infections like pneumonia, as well as bloodstream and urinary tract infection.

Biofilm-associated infections are responsible for thousands of deaths across North America every year. They are hard to eradicate because they secrete a matrix made of sugar molecules which form a kind of armor that acts as a physical and chemical barrier, preventing antibiotics from reaching their target sites within microbes.

We were able to use the microbes own tools against them to attack and destroy the sugar molecules that hold the biofilm together, says the studys co-principal investigator, Don Sheppard, director of the Division of Infectious Diseases at the McGill University Health Center and scientist from the Infectious Diseases and Immunity in Global Health Program.

Rather than trying to develop new individual bullets that target single microbes we are attacking the biofilm that protects those microbes by literally tearing down the walls to expose the microbes living behind them. Its a completely new and novel strategy to tackle this issue, Sheppard says.

This work is the result of a four-year successful collaboration between Sheppards team and scientists in the laboratory of P. Lynne Howell, senior scientist in the Molecular Medicine program at the Hospital for Sick Children (SickKids). They have been working to combat biofilms for several years, focusing on two of the most common organisms responsible for lung infections: a bacterium called Pseudomonas aeruginosa and a fungus called Aspergillus fumigatus.

Infections with these organisms in patients with chronic lung diseases like cystic fibrosis represent an enormous challenge in medical therapy.

While studying machinery that these organisms use to make their biofilms, the scientists discovered enzymes that cut up the sugar molecules, which glue biofilms together.

Microbes use these enzymes to move sugar molecules around and cut them into pieces in order to build and remodel the biofilm matrix, says Sheppard, who is also a professor in the medicine, microbiology, and immunology departments at the university. The researchers found a way to use these enzymes to degrade the sugar armor, exposing the microbe to antibiotics and host defenses.

We made these enzymes into a biofilm destroying machine that we can use outside the microbe where the sugar molecules are found, explains co-first study author Brendan Snarr, a doctoral student in Sheppards laboratory. These enzymes chew away all of the sugar molecules in their path and dont stop until the matrix is destroyed.

Previous attempts to deal with biofilms have had only limited success, mostly in preventing biofilm formation. These enzymes are the first strategy that has ever been effective in eradicating mature biofilms, and that work in mouse models of infection, adds Sheppard.

When we took the enzymes from bacteria and applied them to the fungi, we found that they worked in the same way on the fungi biofilm; which was surprising, says Howell, the studys co-principal investigator, who is also a professor in the biochemistry department at the University of Toronto.

Whats key is that this approach could be a universal way of being able to leverage the microbes own systems for degrading biofilms. This has bigger implications across many microbes, diseases, and infections.

Over 70 percent of hospital-acquired infections are actually associated with biofilms and we simply lack tools to treat them! says Sheppard. According to both lead scientists, the potential of this therapy is enormous and they hope to commercialize it in the coming years.

The Canadian Institutes of Health Research (CIHR); Cystic Fibrosis Canada; the Natural Sciences and Engineering Research Council of Canada (NSERC); Canada Research Chairs Program; the Fonds de recherche Quebec sant (FRQS); SickKids Foundation; and the Canadian Glycomics Network (GlycoNet), part of the Networks of Centres of Excellence of Canada funded the study.

Source: McGill University

See the original post here:

Use biofilm's own enzymes to defeat its 'armor' - Futurity: Research News

Written by AZoNanoJun 23 2017

A new review highlights that tiny nanoparticles provide major potential in detecting and treating disease.

Exosomes can be produced by cells (left), altered before production or after purification (middle), and made in the laboratory (right) depending on their final use. CREDIT: Dr Marta I. Oliveira, INL, Portugal

Exosomes are tiny biological nanoparticles capable of transferring information between cells. These nanoparticles provide noteworthy potential in detecting and treating disease. This is considered to be the most comprehensive overview that has been concluded in this field of research.

According to Dr Steven Conlan from Swansea University, Dr Mauro Ferrari of Houston Methodist Research Institute in Texas, and Dr Ins Mendes Pinto from the International Iberian Nanotechnology Laboratory in Portugal, Regenerative Medicine and Cancer Treatment are the areas that could obtain benefits. Their commissioned paper, which is titled Exosomes as Reconfigurable Therapeutic Systems, was published on June 22nd, 2017, by Cell Press in Trends in Molecular Medicine.

Exosomes are particles developed by all cells present in the body and range from 30-130 nm in size - a nanometer refers to one-billionth of a meter. Exosomes behave as biological signaling systems, carrying proteins, lipids, RNA and DNA and communicating between cells. They are capable of driving biological processes, from transmitting information through breast milk to modulating gene expression.

The complete potential of exosomes is just slowly being revealed even though they were discovered in 1983. The Researchers demonstrate that the possible medical benefits of the nanoparticles fall into three broad categories:

Exosomes have a number of useful properties and one such property refers to their ability to cross barriers such as the plasma membrane of cells, or the brain/blood barrier. This allows them to be ideal for delivering therapeutic molecules in an extremely targeted manner.

The promising benefits of exosomes are discussed in a number of research projects - cited in the paper - under way or already completed, in the following areas:

The team points out that there is more to be done before research into exosomes translates into new treatments and techniques. It is essential to consider the side effects, and a standardized approach ideal for isolating, characterizing and then storing exosomes will have to be developed.

Researchers will also have to make sure that the properties of exosomes do not cause any harm, for example, it is possible for them to transfer drug resistance and also pacify the immune system.

However, the potential indeed is extremely clear, with the Researchers describing exosomes as "increasingly promising".

Professor Steve Conlan of Swansea University Medical School, one of the authors of the paper, said,

"Our survey of research into exosomes shows clearly that they offer enormous potential as a basis for detecting and treating disease.

Further studies are necessary to turn this research into clinical outcomes, but researchers and funders should be very encouraged by our findings. Our own research in Swansea is investigating the use of exosomes and exosome-like synthetic nanoparticles in combatting ovarian and endometrial cancer.

Progress in this field depends on partnership. As the authorship of our own paper illustrates, researchers in different countries are increasingly working together in nanohealth. Swansea University has wider links with Houston and Portuguese based researchers in the field.

It's also important to build partnerships outside academia, in particular with government and companies in this fast-growing sector."

See the original post here:

Exosomes Offer Enormous Potential as a Basis for Detecting and Treating Disease - AZoNano

June 23, 2017

When performed in tandem, two molecular biology laboratory tests distinguish, with near certainty, pancreatic lesions that mimic early signs of cancer but are completely benign. The lesions almost never progress to cancer, so patients may be spared unnecessary pancreatic cancer screenings or operations. The two-test combination is the only one to date that can accurately and specifically identify these benign pancreatic lesions. Its utility was described in one of the largest studies of patients with this form of pancreatic lesion by researchers from Indiana University, Indianapolis. The results of the study now appear in an "article in press" on the Journal of the American College of Surgeons website in advance of print publication.

Between 2 to 3 percent of all patients have some type of pancreatic lesions or cysts revealed on routine abdominal diagnostic radiology scans.1 Nearly all of these patients will later develop pancreatic cancer. The most common and deadliest form of pancreatic cancerpancreatic adenocarcinomahas a five-year survival rate of 12 to 14 percent for early-stage disease and 1 to 3 percent for advanced disease, according to the American Cancer Society.2

A small percentage of patients have serous cystic neoplasms (SCN) that do not harbor malignant potential or progress to cancer. Nevertheless, these patients undergo imaging or other surveillance every six months to spot changes indicative of cancer, or they undergo an operation to remove part of the gland as a precaution because SCN are difficult to find using standard diagnostic methods. More than 60 percent of SCN are not predicted preoperatively3 and 50 to 70 percent are missed or incorrectly diagnosed on radiology scans. 4

However, the researchers determined that two proteins can play a significant role in ruling out precancer and cancer. Vascular endothelial growth factor A (VEGF-A) is a protein associated with promotion of new blood vessel formation. VEGF-A is upregulated in many tumors, and its expression can be correlated with a tumor's stage. Its utility in the diagnosis of pancreatic cysts was discovered by researchers at Indiana University. Carcinoembryonic antigen (CEA) is a protein associated with cell adhesion. It is present in low levels in healthy individuals, but it is increased with certain types of cancers.

Tests for each of these proteins in pancreatic cyst fluid have accurately distinguished SCN from other types of pancreatic lesions. In the present study, VEGF-A, alone, singled out SCN with a sensitivity of 100 percent and specificity of 83.7 percent, and CEA had a 95.5 percent sensitivity and 81.5 percent specificity.

Together, however, the tests approached the gold standard of pathologic testing: The combination had a sensitivity of 95.5 percent and specificity of 100 percent for SCN. Authors of the study concluded that results of the VEGF-A/CEA test could have prevented 26 patients from having unnecessary surgery.

"Every day, surgeons follow patients who have pancreatic cysts that have no risk of cancer but are still worrisome. They perform surgery or conduct diagnostic tests just to make sure they're not wrong. With VEGF-A and CEA, we believe we may have invented a test that can help that group of patients who don't have a risk of cancer get off the testing cycle and avoid surgery which, in and of itself, has a risk of mortality or complications," said C. Max Schmidt, MD, PhD, FACS, study author and professor of surgery and biochemical/molecular biology, Indiana University School of Medicine.

The study included 149 patients who underwent an operation to remove a pancreatic cystic lesion. Twenty-six of these patients had SCN. The diagnosis of each surgical specimen was confirmed by pathologic examination, and samples of pancreatic fluid from all patients were tested for VEGF-A and CEA according to testing protocols for enzyme-linked biochemical analysis of fluids.

The accuracy of the VEGF-A/CEA test needs to be confirmed in large prospective studies. The test itself needs to be performed under quality control conditions. Until a central laboratory is created to meet standards for cystic fluid analysis, Dr. Schmidt recommends that pancreatic surgical programs send specimens to the Indiana University Health Pancreatic Cyst and Cancer Early Detection Center in Indianapolis.

"Many investigators are looking for biological markers to help them understand which pancreatic cysts go on to form cancers. Our laboratory is doing that, but it's also looking for markers to help determine which ones never have the chance of becoming cancers in the first place. These are benign, and they're fooling us into thinking they could become cancers. If we can do that with confidence, we'll find patients who can avoid potentially morbid surgery on the pancreas to remove something that never needed to be removed," Dr. Schmidt said.

In addition to Dr. Schmidt, Rosalie A. Carr, MD; Michele T. Yip-Schneider, PhD; Scott Dolejs, MD; Bradley A. Hancock, BS; Huangbing Wu, BS; and Milan Radovich, PhD, participated in the study.

"FACS" designates that a surgeon is a Fellow of the American College of Surgeons.

Prior to publication, study results were initially reported at the Western Surgical Association 124th Scientific Session in November 2016. This study was supported by the Indiana Clinical and Translational Sciences Institute funded, in part by Grant Number UL1TR001108 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and by a grant from the Lustgarten Foundation and the Indiana Genomics Initiative of Indiana University, supported in part by Lilly Endowment Inc.

Explore further: Game changer: Biomarker identified for noncancerous pancreatic cysts

More information: et al, Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm, Journal of the American College of Surgeons (2017). DOI: 10.1016/j.jamcollsurg.2017.05.003

1 Laffan TA et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR 2008; 191:802-7.

2 American Cancer Society. Pancreatic Survival Rates by Stage: https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html. Accessed June 21, 2017.

3 Kimura W et al. Multicenter study of serous cystic neoplasm of the Japan pancreas society. Pancreas 2012;41:380-7.

4 Bassi C, et al. Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa? World Journal of Surgery 2003;27:319-23.

Researchers at the Indiana University School of Medicine have discovered a highly accurate, noninvasive test to identify benign pancreatic cysts, which could spare patients years of nerve-racking trips to the doctor or potentially ...

A look back at more than half a million patient records has established that patients with pancreatic cysts have a significantly higher overall risk of pancreatic cancer compared to those without such cysts, according to ...

Scientists say they've developed a new blood test for identifying pancreatic cancera step that might eventually allow earlier diagnosis.

Pancreatic cancer has the lowest survival rate among all major cancers, largely because physicians lack diagnostic tools to detect the disease in its early, treatable stages. Now, a team of investigators led by Lev T. Perelman, ...

In a "look-back" analysis of data stored on 130 patients with pancreatic cysts, scientists at Johns Hopkins have used gene-based tests and a fixed set of clinical criteria to more accurately distinguish precancerous cysts ...

Pancreatic ductal adenocarcinoma is one of the most aggressive and deadliest forms of cancer. Treatment options are limited because symptoms typically do not appear until the disease is advanced and complete surgical resection ...

Imagine plopping six cups of coffee grounds on the heads of patients just before they are wheeled into the operating room to have nose or throat surgery?

The first ever randomised trial to investigate why some patients develop infections after their hip or knee replacement surgery, and which type of surgical revision treatment is best is being run by the University of Bristol ...

A new surgical technique devised by MIT researchers could allow prosthetic limbs to feel much more like natural limbs. Through coordination of the patient's prosthetic limb, existing nerves, and muscle grafts, amputees would ...

Ketamine was first introduced into clinical practice by investigators at the University of Michigan in the mid-1960s as a general anesthetic that could offer advantages, such a preserving breathing, not afforded by other ...

Every year, nearly 200,000 Americans turn to surgeons for help with their obesity, seeking bariatric surgery to lose weight and prevent life-threatening health problems.

A three-year study by QUT biomedical researchers in the Paediatric Spine Research Group (PSRG) aims to deepen our understanding of the concepts of comfort by using new techniques to look at how the spine reacts in different ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See the original post here:

Combined molecular biology test is the first to distinguish benign pancreatic lesions - Medical Xpress

June 22, 2017 This figure shows a normal uterine fluid environment during embryo preimplantation. Credit: Zhang, Ying et al., Trends in Molecular Medicine 2017

A developing fetus bathes in a mixture of cellular secretions and proteins unique to its mother's uterus. Before fertilization, the pH of uterine fluid helps create a conducive environment for sperm migration, and afterward, its volume supports the embryo as it implants onto the wall of the uterus. Recent evidence suggests that uterine fluid may play another key role in embryonic development: communicating the mother's outside conditions to the fetus, so that the latter can prepare accordingly. A review of this research appears on June 22 in Trends in Molecular Medicine.

Studies in livestock, rodents, and humans have shown that information from a mother's environment (e.g., food availability, stress, and pollutant exposure) can leave epigenetic tags on the DNA of her fetus, potentially influencing the progression and long-term health of the developing embryo. Scientists have hypothesized that blood flow via the placenta might constitute one way the body communicates the mother's condition to the fetus, yet there is evidence that the fetus can react to changes such as those stemming from the mother's diet long before the establishment of the placenta.

"This suggests the involvement of uterine fluid as the communication medium to transfer information between the maternal environment and the floating embryo," says senior author En-Kui Duan, a reproductive biologist at the Institute of Zoology, Chinese Academy of Sciences. "The preimplantation period is a critical time for programming offspring health, and thus, expecting mothers should keep a good diet and good mood, and stay away from harmful chemicals during this critical window."

While there is much to be learned about how mother-fetus communication takes place, the theory is that information in extracellular vesicles (molecular packages that move from cell to cell) within uterine fluid and tissue deliver their cargo, including microRNAs and amino acids, to the fetus. These molecules may be tagging fetal cell DNA in ways that alter which genes are being expressed, and thus can contribute to "programming" how the embryo and/or placenta develop. Consequently, researchers are interested in learning which specific maternal environmental exposures and/or behaviors could change the composition of molecules transported via the uterine fluid to the fetus.

For example, mouse studies have shown that a low-protein maternal diet can reduce the level of certain amino acids in uterine fluid and affect gene expression of nutrition- transport-related genes. While these changes might prevent malnutrition in the developing embryo, once grown, the mouse offspring are more predisposed to heart disease when compared to animals on a regular diet.

Hongmei Wang, co-senior author of this paper, speculates that uterine fluid could someday be used to analyze or even manipulate what signals are being received by a fetus. "For now, uterine fluid collection is not a standard biomarker, yet many studies have revealed its potential role for non-invasive analysis, and we also see great potential in it," she says. "One, it can be screened by using ultrasound recording coupled with computational/biomechanical analysis; and two, uterine fluid can also be collected during an endometrial examination."

Explore further: Female diet alters the nutrient composition of fluid in the womb

More information: Trends in Molecular Medicine, Zhang, Ying et al.: "Uterine Fluid in Pregnancy: A Biological and Clinical Outlook." http://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(17)30080-1 , DOI: 10.1016/j.molmed.2017.05.002

Scientists at the University of Soutahmpton's Faculty of Medicine have discovered that maternal diet affects the nutrient composition of fluid in the womb of women and thus may aid in the development of nutritional interventions ...

Looking to improve the success rate of assisted reproductive technologies, researchers at Baylor College of Medicine investigated in more detail the mechanism involved in successful embryo implantation, an essential component ...

Mutations that have been linked to endometrial cancer can be found in the uterine lavage fluid of pre- and post-menopausal women both with and without detectable cancer, according to a study published in PLOS Medicine by ...

If the mother is stressed over a longer period of time during pregnancy, the concentration of stress hormones in amniotic fluid rises, as proven by an interdisciplinary team of researchers from the University of Zurich. Short-term ...

Scientists have identified a crucial molecular key to healthy embryo implantation and pregnancy in a study that may offer new clues about the medical challenges of infertility/subfertility, abnormal placentation, and placenta ...

UC San Francisco researchers have visualized the earliest stages of pregnancy in unprecedented detail in laboratory animals and human tissue using new laboratory imaging techniques that promise to enable rapid progress in ...

A developing fetus bathes in a mixture of cellular secretions and proteins unique to its mother's uterus. Before fertilization, the pH of uterine fluid helps create a conducive environment for sperm migration, and afterward, ...

Scientists studying a mystery link between the dangerous pregnancy complication pre-eclampsia and an increased risk of heart disease in later life for both mother and child have uncovered important new clues.

With advances in prenatal testing it's now possible to find out whether a pregnancy will result in a male or female baby as early as eight weeks' gestation.

How difficult is it to conceive? According to a widely-held view, fewer than one in three embryos make it to term, but a new study from a researcher at the University of Cambridge suggests that human embryos are not as susceptible ...

Couples who are undergoing pre-implantation genetic diagnosis (PGD) in order to avoid transmission of inherited diseases, such as Duchenne muscular dystrophy or cystic fibrosis, should also have their embryos screened for ...

Cesarean delivery is the most common inpatient surgical procedure in the United States, with 1.4 million c-sections performed each year. Opioids, most commonly oxycodone, are the standard pain medications prescribed to women ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Continue reading here:

The biology of uterine fluid: How it informs the fetus of mom's world - Medical Xpress

June 22, 2017 Exosomes can be produced by cells (left), altered before production or after purification (middle), and made in the laboratory (right) depending on their final use. Credit: Dr Marta I. Oliveira, INL, Portugal

Tiny nanoparticles offer significant potential in detecting and treating disease - new review

Exosomes - tiny biological nanoparticles which transfer information between cells - offer significant potential in detecting and treating disease, the most comprehensive overview so far of research in the field has concluded.

Areas which could benefit include cancer treatment and regenerative medicine, say Dr Steven Conlan from Swansea University, Dr Mauro Ferrari of Houston Methodist Research Institute in Texas, and Dr Ins Mendes Pinto from the International Iberian Nanotechnology Laboratory in Portugal. Their commissioned paper, Exosomes as Reconfigurable Therapeutic Systems, is published today by Cell Press in Trends in Molecular Medicine.

Exosomes are particles produced by all cells in the body and are from 30-130 nanometres in size - a nanometre is one-billionth of a metre. They act as biological signalling systems, communicating between cells, carrying proteins, lipids, DNA and RNA. They drive biological processes, from modulating gene expression to transmitting information through breast milk.

Though discovered in 1983, the full potential of exosomes is only gradually being revealed. The researchers show that the nanoparticles' possible medical benefits fall into three broad categories:

One of the most useful properties of exosomes is that they are able to cross barriers such as the plasma membrane of cells, or the blood/brain barrier. This makes them well-suited to delivering therapeutic molecules in a very targeted way.

The potential benefits of exosomes can be seen in the wide range of research projects - cited in the paper - already either completed or under way, in areas such as:

The team caution that there is more to do before research into exosomes translates into new techniques and treatments. Side-effects need to be considered, and a standardised approach to isolating, characterising and storing exosomes will need to be developed.

Researchers will also need to ensure that the properties of exosomes do not end up causing harm: for example they can transfer drug resistance and pacify the immune system.

Nevertheless, the potential is very clear, with the team describing exosomes as "increasingly promising".

Professor Steve Conlan of Swansea University Medical School, one of the authors of the paper, said:

"Our survey of research into exosomes shows clearly that they offer enormous potential as a basis for detecting and treating disease.

Further studies are necessary to turn this research into clinical outcomes, but researchers and funders should be very encouraged by our findings. Our own research in Swansea is investigating the use of exosomes and exosome-like synthetic nanoparticles in combatting ovarian and endometrial cancer.

Progress in this field depends on partnership. As the authorship of our own paper illustrates, researchers in different countries are increasingly working together in nanohealth. Swansea University has wider links with Houston and Portuguese based researchers in the field.

It's also important to build partnerships outside academia, in particular with government and companies in this fast-growing sector."

Explore further: New approach for the capture of tumor-derived exosomes from a prostate cancer cell line

More information: R. Steven Conlan et al. Exosomes as Reconfigurable Therapeutic Systems, Trends in Molecular Medicine (2017). DOI: 10.1016/j.molmed.2017.05.003

In a new paper in Springer's Journal of Materials Science, researchers at Washington State University report a new approach for the effective capture of tumor-derived exosomes from a prostate cancer cell line. Exosomes are ...

Size really does matter when it comes to the mechanisms that cells use to communicate with each other, according to pioneering new nanobiotechnology research which has important implications for the diagnosis and treatment ...

Genetic manipulation of exosomes, virus-sized particles released by all cells, may offer a new therapeutic approach to treating pancreatic cancer, according to a study at The University of Texas MD Anderson Cancer Center.

A new study in rats shows that stem cell secretions, called exosomes, appear to protect cells in the retina, the light-sensitive tissue in the back of the eye. The findings, published in Stem Cells Translational Medicine, ...

Exosomes, tiny, virus-sized particles released by cancer cells, can bioengineer micro-RNA (miRNA) molecules resulting in tumor growth. They do so with the help of proteins, such as one named Dicer. New research from The University ...

The cancer drug paclitaxel just got more effective. For the first time, researchers from the University of North Carolina at Chapel Hill have packaged it in containers derived from a patient's own immune system, protecting ...

Biomedical engineers have built simple machines out of DNA, consisting of arrays whose units switch reversibly between two different shapes.

Tiny nanoparticles offer significant potential in detecting and treating disease - new review

Nanotechnologists from Rice University and China's Tianjin University have used 3-D laser printing to fabricate centimeter-sized objects of atomically thin graphene.

Versatile, light-weight materials that are both strong and resilient are crucial for the development of flexible electronics, such as bendable tablets and wearable sensors. Aerogels are good candidates for such applications, ...

(Phys.org)Researchers have built a new type of "neuron transistor"a transistor that behaves like a neuron in a living brain. These devices could form the building blocks of neuromorphic hardware that may offer unprecedented ...

(Phys.org)Nanowires fashioned from DNA (deoxyribonucleic acid)one of several type of molecular nanowires incorporating repeating molecular unitsare exactly that: Geometrically wire-like DNA-based nanostructures defined ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Visit link:

Tiny nanoparticles offer significant potential in detecting/treating disease new review of work on exosomes - Phys.Org