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  • richardmitnick 2:42 pm on May 24, 2017 Permalink | Reply
    Tags: , , Cancer, , New imaging technique aims to ensure surgeons completely remove cancer,   

    From Wash U: “New imaging technique aims to ensure surgeons completely remove cancer” 

    Wash U Bloc

    Washington University in St.Louis

    Caltech Logo

    Caltech

    May 17, 2017
    Tamara Bhandari
    tbhandari@wustl.edu

    1
    A new imaging technique based on light and sound produces images doctors can use to distinguish cancerous breast tissue (below the dotted blue line) from normal tissue more quickly than is currently possible. Pathologists routinely inspect surgical specimens to make sure all cancerous tissue has been removed. The new technique (right) produces images as detailed and accurate as traditional methods (left), but in far less time. The researchers are working to make the technique fast enough to be used during a surgery, so patients don’t have to return for a second surgery. (Image: Terence T.W. Wong)

    Of the quarter-million women diagnosed with breast cancer every year in the United States, about 180,000 undergo surgery to remove the cancerous tissue while preserving as much healthy breast tissue as possible.

    However, there’s no accurate method to tell during surgery whether all of the cancerous tissue has been successfully removed. The gold-standard analysis takes a day or more, much too long for a surgeon to wait before wrapping up an operation. As a result, about a quarter of women who undergo lumpectomies receive word later that they will need a second surgery because a portion of the tumor was left behind.

    Now, researchers at Washington University School of Medicine in St. Louis and California Institute of Technology report that they have developed a technology to scan a tumor sample and produce images detailed and accurate enough to be used to check whether a tumor has been completely removed.

    Called photoacoustic imaging, the new technology takes less time than standard analysis techniques. But more work is needed before it is fast enough to be used during an operation.

    The research is published May 17 in Science Advances.

    “This is a proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing,” said Deborah Novack, MD, PhD, an associate professor of medicine, and of pathology and immunology, and a co-senior author on the study.

    The researchers are working on improvements that they expect will bring the time needed to scan a specimen down to 10 minutes, fast enough to be used during an operation. The current gold-standard method of analysis, which is based on preserving the tissue and then staining it to make the cells easier to see, hasn’t gotten any faster since it was first developed in the mid-20th century.

    For solid tumors in most parts of the body, doctors use a technique known as a frozen section to do a quick check of the excised lump during the surgery. They look for a thin rim of normal cells around the tumor. Malignant cells at the margins suggest the surgeon missed some of the tumor, increasing the chances that the disease will recur.

    But frozen sections don’t work well on fatty specimens like those from the breast, so the surgeon must finish a breast lumpectomy without knowing for sure how successful it was.

    “Right now, we don’t have a good method to assess margins during breast cancer surgeries,” said Rebecca Aft, MD, PhD, a professor of surgery and a co-senior author on the study. Aft, a breast cancer surgeon, treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

    Currently, after surgery a specimen is sent to a pathologist, who slices it, stains it and inspects the margins for malignant cells under a microscope. Results are sent back to the surgeon within a few days.

    To speed up the process, the researchers took advantage of a phenomenon known as the photoacoustic effect. When a beam of light of the right wavelength hits a molecule, some of the energy is absorbed and then released as sound in the ultrasound range. These sound waves can be detected and used to create an image.

    “All molecules absorb light at some wavelength,” said co-senior author Lihong Wang, who conducted the work when he was a professor of biomedical engineering at Washington University’s School of Engineering & Applied Science. He is now at Caltech. “This is what makes photoacoustic imaging so powerful. Essentially, you can see any molecule, provided you have the ability to produce light of any wavelength. None of the other imaging technologies can do that. Ultrasound will not do that. X-rays will not do that. Light is the only tool that allows us to provide biochemical information.”

    The researchers tested their technique by scanning slices of tumors removed from three breast cancer patients. For comparison, they also stained each specimen according to standard procedures.

    The photoacoustic image matched the stained samples in all key features. The architecture of the tissue and subcellular detail such as the size of nuclei were clearly visible.

    “It’s the pattern of cells – their growth pattern, their size, their relationship to one another – that tells us if this is normal tissue or something malignant,” Novack said. “Overall, the photoacoustic images had a lot of the same features that we see with standard staining, which means we can use the same criteria to interpret the photoacoustic imaging. We don’t have to come up with new criteria.”

    Having established that photoacoustic techniques can produce usable images, the researchers are working on reducing the scanning time.

    “We expect to be able to speed up the process,” Wang said. “For this study, we had only a single channel for emitting light. If you have multiple channels, you can scan in parallel and that reduces the imaging time. Another way to speed it up is to fire the laser faster. Each laser pulse gives you one data point. Faster pulsing means faster data collection.”

    Aft, Novack and Wang are applying for a grant to build a photoacoustic imaging machine with multiple channels and fast lasers.

    “One day we think we’ll be able to take a specimen straight from the patient, plop it into the machine in the operating room and know in minutes whether we’ve gotten all the tumor out or not,” Aft said. “That’s the goal.”

    This work was supported by the National Institutes of Health, grant number DP1 EB016986 and R01 CA186567, and by Washington University’s Siteman Cancer Center’s 2014 Research Development Award.

    See the full article here .

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    The California Institute of Technology (commonly referred to as Caltech) is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. “The mission of the California Institute of Technology is to expand human knowledge and benefit society through research integrated with education. We investigate the most challenging, fundamental problems in science and technology in a singularly collegial, interdisciplinary atmosphere, while educating outstanding students to become creative members of society.”


    Caltech campus

    Wash U campus
    Wash U campus

    Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

    Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

     
  • richardmitnick 5:35 am on May 23, 2017 Permalink | Reply
    Tags: , Cancer, , New cancer drug can prevent reactions to common airborne allergens, , Possibilities for food allergies   

    From Northwestern: “New cancer drug can prevent reactions to common airborne allergens” 

    Northwestern U bloc
    Northwestern University

    May 22, 2017
    Kristin Samuelson

    Targeted cancer treatment might treat food allergies, too.

    1
    A person’s skin is tested for allergies. No image credit.

    A cancer drug for patients with certain types of leukemia and lymphoma can also prevent reactions to some of the most common airborne allergies, according to a recent Northwestern Medicine study. The promising data from this pilot study could have greater implications for adults with food allergies.

    The cancer patients who were allergic to allergens such as cat dander and ragweed saw their allergic skin test reactivity reduced by 80 to 90 percent in one week, and this persisted with continued use of the drug for at least one to two months. The findings were published in the Journal of Allergy and Clinical Immunology in May.

    “It almost completely knocked out the patients’ skin test and blood cell allergic reactivity,” said senior author Dr. Bruce Bochner, the Samuel M. Feinberg Professor of Medicine at Northwestern University Feinberg School of Medicine.

    This FDA-approved drug, ibrutinib, is currently on the market as a successful and less-toxic alternative to chemotherapy for patients with chronic lymphocytic leukemia and mantle cell lymphoma. In this recent study, Bochner and his team performed traditional allergy skin tests and the basophil activation test, a related allergy test using blood cells, on cancer patients before they had taken ibrutinib and again after one week and after one to two months of taking it.

    A rather unlikely pairing – cancer and allergies – Bochner thought to test if a cancer drug could prevent allergic reactions by collaborating with Feinberg’s oncology department.

    He knew that the generally well-tolerated cancer drug was successful in blocking a protein inside a cell called Bruton’s Tyrosine Kinase (BTK). BTK plays a crucial role in B cell activation, growth and maturation and mast cell and basophil activation, the latter two cells being responsible for immediate allergic reactions. Bochner teamed up with Northwestern oncologist Dr. Leo Gordon and colleagues to test if this BTK inhibitor could shut down an enzyme inside cells that is involved when you have an allergic reaction.

    “Ibrutinib is considered a game changer in these two types of cancers,” said Gordon, the Abby and John Friend Professor of Cancer Research at Feinberg. “We understood that it might have some biologic effects in what Bruce is interested in, so we were happy to participate in his study. It’s an interesting repurposing of that drug.”

    While the study was small – only two patients qualified out of about 35 that were screened for allergies – the implications are much larger for later phases of this study. Bochner and his colleagues Drs. Anne Marie Singh and Melanie Dispenza are now testing how successful the drug is at targeting allergies to food, such as tree nuts and peanuts.

    “Preventing or lessening the severity of an allergic reaction to a food you’ve ingested that you’re allergic to is kind of the holy grail of food allergy treatment,” Bochner said. “I don’t know if this or similar drugs will ever make it possible for a peanut-allergic person to eat peanut butter and jelly sandwiches, but we’re excited to use this approach to teach us how to lessen the risks of food allergy reactions.”

    Currently, the study is being expanded to adults with food allergy to see if their skin test and basophil activation test responses show a similar reduction with just a few doses of ibrutinib and how long such benefits might last. If the results are favorable, the next step would be to get funding to actually test whether taking a BTK inhibitor will improve the ability of food-allergic adults to eat foods they’re allergic to.

    “The hope is that drugs like BTK inhibitors will protect people with food allergies from having anaphylaxis, or at least increase how much of that food they can eat without reacting,” Bochner said. “Maybe they’ll increase from being able to eat just one peanut to 10 before they react. Or maybe they’ll be able to eat a full meal’s worth of peanuts. We want to know if this would safely change their actual ability to eat foods that they currently need to avoid.”

    The study was funded by a 2016 Dixon Translational Research Grant.

    See the full article here .

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    Northwestern South Campus
    South Campus

    On May 31, 1850, nine men gathered to begin planning a university that would serve the Northwest Territory.

    Given that they had little money, no land and limited higher education experience, their vision was ambitious. But through a combination of creative financing, shrewd politicking, religious inspiration and an abundance of hard work, the founders of Northwestern University were able to make that dream a reality.

    In 1853, the founders purchased a 379-acre tract of land on the shore of Lake Michigan 12 miles north of Chicago. They established a campus and developed the land near it, naming the surrounding town Evanston in honor of one of the University’s founders, John Evans. After completing its first building in 1855, Northwestern began classes that fall with two faculty members and 10 students.
    Twenty-one presidents have presided over Northwestern in the years since. The University has grown to include 12 schools and colleges, with additional campuses in Chicago and Doha, Qatar.

    Northwestern is recognized nationally and internationally for its educational programs.

     
  • richardmitnick 8:45 pm on May 22, 2017 Permalink | Reply
    Tags: , “Driver” mutations, “Passenger” mutations, Cancer, Cancer is a disease of the genome, Genomic medicine requires massive data sharing and analysis, , Slit/Robo signaling, Treehouse Childhood Cancer Initiative, , Understanding the pathways that drive cancer   

    From UCSC: Cancer in the Cross Hairs” 

    UC Santa Cruz

    UC Santa Cruz

    1

    UC Santa Cruz may not have a medical school, but its scientists are tackling some of the most challenging problems in cancer genomics, drug discovery, and basic cancer biology

    5.18.17
    Tim Stephens

    Scott Lokey is not easily discouraged. In fact, he seems to thrive on scientific challenges, like taking on what the pharmaceutical industry calls “undruggable targets.” The term applies to molecules known to play a key role in disease but not susceptible to control by the kinds of small molecules that make good drugs.

    Lokey, a professor of chemistry and biochemistry and director of the Chemical Screening Center at UC Santa Cruz, is working with compounds that he thinks could overcome the obstacles presented by “undruggable” targets. If successful, his work could lead to a whole new class of drugs to fight cancer and other diseases.

    One such target is the retinoblastoma tumor suppressor protein, which normally puts the brakes on cell division. Its function is disrupted in most human cancers, allowing cancer cells to proliferate.


    Scott Lokey, professor of chemistry and biochemistry at UC Santa Cruz and director of the UCSC Chemical Screening Center, discusses how UCSC researchers are taking on “undruggable” targets.

    “The retinoblastoma protein is just the tip of the iceberg. There’s a huge inventory of potential targets that we haven’t been able to get at with conventional drugs,” says Lokey. “I actually get the majority of my funding from pharmaceutical companies for work on undruggable targets.”

    Taking on challenging drug targets is just one way to make progress against cancer. Researchers at UC Santa Cruz are attacking the disease from every angle. While the Chemical Screening Center searches for new cancer-fighting compounds, biologists are identifying new targets for the next generation of cancer drugs, and genomics experts are harnessing the power of big data to usher in a new era of precision therapies. The campus may not have a medical school, but that doesn’t keep its scientists and engineers from working at the cutting edge of biomedical research.

    All advances in cancer treatment­—from the development of new therapies and diagnostic tools to the use of genomics to guide treatment decisions—are rooted in understanding the fundamental biology of cancer cells.

    Cancer is a disease of the genome, caused by genetic changes that lead to uncontrolled growth and proliferation of tumor cells. Genomic analysis of tumor cells can reveal the genetic errors driving a patient’s cancer, but the enormous diversity of genetic abnormalities found in cancer cells makes interpreting the genomic data a huge challenge. Researchers at the UC Santa Cruz Genomics Institute are developing sophisticated computational methods for analyzing genomic data to help doctors choose the most effective drugs for individual patients.

    Known as “cancer genomics,” it’s a powerful approach that builds on decades of ongoing work by biologists to understand exactly how genetic changes drive cancer.

    Pathways to cancer

    The genetic abnormalities in cancer cells disrupt the signaling networks or “pathways” that regulate cellular activities. The life of a cell is orchestrated by a vast interconnected web of these pathways. Each pathway involves a complex series of interactions between cellular proteins, complete with feedback loops, cascading amplifications, and intersections with other pathways. Some of the proteins in these pathways have crucial interactions with the cell’s genetic material: the chromosomal DNA where genes are encoded and the RNA molecules involved in gene expression.

    Biologists like Lindsay Hinck, Doug Kellogg, Jeremy Sanford, and others in UCSC’s Department of Molecular, Cell, and Developmental Biology (MCD Biology) have made remarkable progress in unraveling the details of signaling pathways and their roles in cancer. Hinck’s lab, for example, has been studying the “Slit/Robo” pathway, which controls breast development and is disrupted in breast cancer and other cancers.


    Lindsay Hinck, professor of molecular, cell and developmental biology at UC Santa Cruz and co-director of the Institute for the Biology of Stem Cells discusses how understanding the fundamentals of cancer biology is the key to developing new cancer therapies.

    Slit/Robo signaling is actually involved in several critical pathways controlling cell proliferation and migration. The tumor suppressing effects of these pathways make them potential targets for drug development efforts. Hinck’s investigations of these pathways continue to reveal new insights, most recently on their roles in hormonal regulation of breast cancer cells.

    “Understanding how subpopulations of breast cancer cells respond to hormones such as estrogen and develop resistance to anti-estrogen treatments is likely to be very important for the next level of drug targets,” Hinck says.

    Clinical applications

    Working out the cellular signaling pathways involved in cancer can lead to clinical applications in a variety of ways. The most obvious is identifying a key molecule as a promising target for drug development, which often leads to more focused research on that particular molecule.

    Much of Seth Rubin’s research, for example, is focused on the retinoblastoma tumor suppressor protein (called Rb). Rb is a central player in many signaling pathways that are disrupted in cancer cells. It is called a tumor suppressor because it blocks the proliferation of abnormal cancer cells.

    “Rb is a stop sign that keeps cells from proliferating, so cancer cells have to turn it into a go sign,” explains Rubin, a professor of chemistry and biochemistry who has worked out the detailed structure of Rb and how it interacts with other proteins.

    Rubin has been working with Lokey’s lab and the Chemical Screening Center, developing a strategy to directly activate the Rb protein with a drug and turn it back into a stop sign. There are two issues that make this especially challenging. One is the goal of activating a protein that isn’t functioning properly. Most drugs are inhibitors that interfere with the function of their target; many cancer therapies target overactive pathways and aim to shut them down using inhibitors.

    “It’s a lot easier to knock down the function of something with a drug, because you’re basically just throwing a wrench into the system, whereas fixing something that’s not working is a lot harder to do,” Rubin explains.

    The other challenge is structural. Most drugs are small molecules that easily penetrate cells and block the target molecule by binding to its active site, typically just a deep pocket in its structure. “The standard analogy is that it fits like a lock and key, but it’s more like a baseball in a glove. That describes the vast majority of drugs and their targets,” Lokey says.

    But the active sites of many undruggable targets like Rb are large and complex, so an effective drug would have to be correspondingly large and interact with the target in complex ways, not just fit into a pocket. Lokey’s lab is working on the synthesis of large molecules that can bind to more complex targets and can also penetrate cells.

    In work led by Cameron Pye, a graduate student in Lokey’s lab, the team developed an assay to screen large numbers of these compounds (called cyclic peptides) for their ability to activate Rb. The lab has begun preliminary screening through a collaboration with Roche NimbleGen.

    “We’ve gone from no hits with small molecules to getting some hits for Seth’s target through this collaboration,” Lokey says. “Industry funding has been good for us. They have amazing technology for building these libraries of compounds.”

    Marking the way

    Understanding the pathways that drive cancer cells can yield not only drug targets but also clinically useful “biomarkers” to guide prognosis and therapeutic decision-making. In Zhu Wang’s research on prostate cancer, for example, he is studying the molecular mechanisms that make some prostate cancers highly aggressive. Many prostate cancers are slow-growing and may never threaten a patient’s health.

    “My work focuses on the cell types and molecular mechanisms that give rise to more aggressive cancers. The clinical applications could be new biomarkers that can be used to distinguish aggressive cancers from indolent cancers,” says Wang, an assistant professor of MCD biology. “Finding a molecular signature that is predictive of aggressive prostate cancer would have great prognostic value.”

    Pathway analysis plays a critical role in cancer genomics and has been a major focus of research in Josh Stuart’s lab. Stuart, the Baskin Professor of biomolecular engineering, recently published a study of metastatic prostate cancer yielding a detailed map of the abnormal signaling pathways that enable prostate cancer cells to proliferate and evade treatment. In collaboration with a team at UCLA, Stuart’s lab developed a novel computational analysis to produce personalized diagrams of the signaling pathways driving a patient’s cancer cells.

    “For now it’s a research tool, but the hope is to have a strategy like this to use in the clinic,” Stuart says. “These mutations in the genome create a lot of havoc in the cell, and trying to interpret the genomic information can be overwhelming. You need the computer to help you make sense of it and find the Achilles heel in the network that you can hit with a drug.”

    Drivers and passengers

    A persistent problem in cancer genomics has been distinguishing “driver” mutations from “passenger” mutations. Cancer cells often accumulate large numbers of genetic mutations that do not play a role in driving the uncontrolled growth. These passenger mutations effectively create static that interferes with the signal for mutations that are the real drivers of cancer. Aggregating data from large numbers of patients can give researchers enough statistical power to identify driver mutations.

    “Genomic medicine requires massive data sharing and analysis,” says David Haussler, professor of biomolecular engineering and director of the Genomics Institute. For years, Haussler has been an evangelist for data sharing to advance genomic medicine. In 2012, his team created the first public cancer genome database for the National Cancer Institute, the Cancer Genomics Hub. A year later, he cofounded the Global Alliance for Genomics and Health, an international nonprofit that is helping establish the infrastructure for data sharing in genomic medicine.

    Research led by the Genomics Institute has demonstrated the value of massive datasets in cancer genomics. In 2014, a groundbreaking study led by Stuart’s lab, based on analyses of molecular data from thousands of patients with 12 different tumor types, revealed that classifying tumors based on molecular subtypes, rather than the traditional tissue-of-origin system (i.e., breast cancer, lung cancer, etc.), could lead to different therapeutic options for as many as one in ten cancer patients. This type of “pan-cancer” analysis is only possible with data from large numbers of patients.

    Childhood cancers are rare, which makes it especially hard to assemble data from large numbers of patients. The Genomics Institute launched the Treehouse Childhood Cancer Initiative to address this problem and recently received a major grant from St. Baldrick’s Foundation to support the effort. A clinical pilot project launched in 2015 showed that real-time data sharing can identify new and better treatment options for children with cancer.


    Treehouse Childhood Cancer Initiative aims to make a huge difference in the world of pediatric cancer.

    “We need to think beyond sharing data after the research is published, which can take years, and move toward sharing patient genomic data in real time,” says Treehouse cofounder Olena Morozova, a research scientist at the Genomics Institute. “With real-time data sharing, the pediatric cancer community is poised to lead the way in revolutionizing how we share genomic data to benefit patients right now.”

    No silver bullet

    Experts have long understood that there is no silver bullet for cancer and that it is not, in fact, one disease but hundreds of diseases with different causes requiring different approaches to treatment. At the same time, there are good reasons to be optimistic about the prospects for more effective cancer treatments.

    “People sometimes overlook the fact that we are having success and bringing on new cancer therapies all the time,” Hinck says. “The problem is that every type of cancer is heterogeneous–there are at least five types of breast cancer, and some would say ten or 15, depending on how you classify them. We still have a lot to understand, and that’s why we need to keep doing this fundamental research.”

    Cancer immunotherapy, which uses drugs to coax the patient’s own immune system to eliminate the cancer, has shown particular promise in recent clinical trials. Haussler is collaborating with protein chemist Nik Sgourakis to advance immunotherapy using genomics. They are developing new computational tools for analyzing tumor genomes to predict which mutated proteins are displayed on the surface of tumor cells where they can be “seen” by the body’s immune system. These predictions are then evaluated on patient samples from medical collaborators at NIH, UCLA, and Children’s Hospital of Philadelphia. With this information, it may be possible to more specifically train the immune system to find and eliminate tumor cells, Haussler said.

    Whether in cancer genomics, drug discovery, or basic cancer biology, cancer researchers at UC Santa Cruz tend to tackle the most challenging problems and pursue ambitious projects.

    “We have a unique perspective based on who we are and the expertise we have here at UCSC,” says Kellogg, professor of MCD biology.

    For example, UC Santa Cruz is known as a leading center for research on the biology of RNA, and that has attracted talented young faculty such as Angela Brooks in biomolecular engineering and Jeremy Sanford in MCD biology, who are investigating the role of RNA in gene regulatory networks and cancer. “We’ve always had strength in RNA biology, and now there’s a good core of people here who are thinking more about RNA and disease. It’s an area that has not been well studied in cancer biology,” Sanford says.

    “You could say we tackle the hard problems and take on things that no one else is doing,” says Hinck.

    Most of the cancer researchers at UC Santa Cruz are funded by major grants from the National Institutes of Health (NIH), including the National Cancer Institute. As the single largest funding source for UCSC research, NIH awarded nearly $40 million in grants to support campus research projects in 2015-16.

    Private foundations like St. Baldrick’s are also important sources of funding for cancer research. The Santa Cruz Cancer Benefit Group (SCCBG), a local charity supporting cancer research and patient care, has awarded small grants to a number of UCSC faculty, including Rubin, Lokey, Hinck, and Wang. These grants fund pilot studies, the results of which can lead to much larger grants from NIH and other major funders.

    “That kind of seed funding is really important,” Rubin says.

    SCCBG funding has enabled Lokey to start a new project searching for compounds that could improve the effectiveness of cancer immunotherapy drugs. Immunotherapy drugs known as checkpoint inhibitors have taken the oncology world by storm, he says, but they work for only a subset of patients. Lokey hopes to find compounds that can make tumors more visible to the patient’s immune system.

    “It’s the kind of high risk, high reward research that’s hard to get funding for,” he says. “If we’re successful, though, it could really have a big impact.”

    Credits:

    Writing: Tim Stephens
    Video: Tim Stephens, Lisa Nielsen, Lucid Sound & Picture
    Photos: Carolyn Lagatutta
    Design and development: Rob Knight
    Project managers: Sherry Main, Scott Hernandez-Jason, Tim Stephens

    See the full article here .

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    UCO Lick Shane Telescope
    UCO Lick Shane Telescope interior
    Shane Telescope at UCO Lick Observatory, UCSC

    Lick Automated Planet Finder telescope, Mount Hamilton, CA, USA

    Lick Automated Planet Finder telescope, Mount Hamilton, CA, USA

    UC Santa Cruz campus
    The University of California, Santa Cruz, opened in 1965 and grew, one college at a time, to its current (2008-09) enrollment of more than 16,000 students. Undergraduates pursue more than 60 majors supervised by divisional deans of humanities, physical & biological sciences, social sciences, and arts. Graduate students work toward graduate certificates, master’s degrees, or doctoral degrees in more than 30 academic fields under the supervision of the divisional and graduate deans. The dean of the Jack Baskin School of Engineering oversees the campus’s undergraduate and graduate engineering programs.

    UCSC is the home base for the Lick Observatory.

    Lick Observatory's Great Lick 91-centimeter (36-inch) telescope housed in the South (large) Dome of main building
    Lick Observatory’s Great Lick 91-centimeter (36-inch) telescope housed in the South (large) Dome of main building

    Search for extraterrestrial intelligence expands at Lick Observatory
    New instrument scans the sky for pulses of infrared light
    March 23, 2015
    By Hilary Lebow
    1
    The NIROSETI instrument saw first light on the Nickel 1-meter Telescope at Lick Observatory on March 15, 2015. (Photo by Laurie Hatch) UCSC Lick Nickel telescope

    Astronomers are expanding the search for extraterrestrial intelligence into a new realm with detectors tuned to infrared light at UC’s Lick Observatory. A new instrument, called NIROSETI, will soon scour the sky for messages from other worlds.

    “Infrared light would be an excellent means of interstellar communication,” said Shelley Wright, an assistant professor of physics at UC San Diego who led the development of the new instrument while at the University of Toronto’s Dunlap Institute for Astronomy & Astrophysics.

    Wright worked on an earlier SETI project at Lick Observatory as a UC Santa Cruz undergraduate, when she built an optical instrument designed by UC Berkeley researchers. The infrared project takes advantage of new technology not available for that first optical search.

    Infrared light would be a good way for extraterrestrials to get our attention here on Earth, since pulses from a powerful infrared laser could outshine a star, if only for a billionth of a second. Interstellar gas and dust is almost transparent to near infrared, so these signals can be seen from great distances. It also takes less energy to send information using infrared signals than with visible light.

    5
    UCSC alumna Shelley Wright, now an assistant professor of physics at UC San Diego, discusses the dichroic filter of the NIROSETI instrument. (Photo by Laurie Hatch)

    Frank Drake, professor emeritus of astronomy and astrophysics at UC Santa Cruz and director emeritus of the SETI Institute, said there are several additional advantages to a search in the infrared realm.

    “The signals are so strong that we only need a small telescope to receive them. Smaller telescopes can offer more observational time, and that is good because we need to search many stars for a chance of success,” said Drake.

    The only downside is that extraterrestrials would need to be transmitting their signals in our direction, Drake said, though he sees this as a positive side to that limitation. “If we get a signal from someone who’s aiming for us, it could mean there’s altruism in the universe. I like that idea. If they want to be friendly, that’s who we will find.”

    Scientists have searched the skies for radio signals for more than 50 years and expanded their search into the optical realm more than a decade ago. The idea of searching in the infrared is not a new one, but instruments capable of capturing pulses of infrared light only recently became available.

    “We had to wait,” Wright said. “I spent eight years waiting and watching as new technology emerged.”

    Now that technology has caught up, the search will extend to stars thousands of light years away, rather than just hundreds. NIROSETI, or Near-Infrared Optical Search for Extraterrestrial Intelligence, could also uncover new information about the physical universe.

    “This is the first time Earthlings have looked at the universe at infrared wavelengths with nanosecond time scales,” said Dan Werthimer, UC Berkeley SETI Project Director. “The instrument could discover new astrophysical phenomena, or perhaps answer the question of whether we are alone.”

    NIROSETI will also gather more information than previous optical detectors by recording levels of light over time so that patterns can be analyzed for potential signs of other civilizations.

    “Searching for intelligent life in the universe is both thrilling and somewhat unorthodox,” said Claire Max, director of UC Observatories and professor of astronomy and astrophysics at UC Santa Cruz. “Lick Observatory has already been the site of several previous SETI searches, so this is a very exciting addition to the current research taking place.”

    NIROSETI will be fully operational by early summer and will scan the skies several times a week on the Nickel 1-meter telescope at Lick Observatory, located on Mt. Hamilton east of San Jose.

    The NIROSETI team also includes Geoffrey Marcy and Andrew Siemion from UC Berkeley; Patrick Dorval, a Dunlap undergraduate, and Elliot Meyer, a Dunlap graduate student; and Richard Treffers of Starman Systems. Funding for the project comes from the generous support of Bill and Susan Bloomfield.

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    UCSC is the home base for the Lick Observatory.

     
  • richardmitnick 3:13 pm on May 22, 2017 Permalink | Reply
    Tags: A lack of the protein citrin slows children's growth; blocking it in cancer slows tumor growth., , Cancer, Dr. Ayelet Erez, , ,   

    From Weizmann: Women in STEM – “Rare Genetic Defect May Lead to Cancer Drug” Dr. Ayelet Erez 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    17.05.2017
    No writer credit found

    1
    Dr. Ayelet Erez says rare genetic diseases provide a lens on cancer.

    A lack of the protein citrin slows children’s growth; blocking it in cancer slows tumor growth.

    The path to understanding what goes wrong in cancer could benefit from a detour through studies of rare childhood diseases. Dr. Ayelet Erez explains that cancer generally involves dozens – if not hundreds – of mutations, and sorting out the various functions and malfunctions of each may be nearly impossible. Rare childhood diseases, in contrast, generally involve mutations to a single gene. Erez, a geneticist and medical doctor who treats families with genetic cancer in addition to heading a research lab in the Weizmann Institute of Science’s Biological Regulation Department, says that children with rare genetic syndromes may serve as a “lens” when trying to understand the role of a specific gene in a complex disease such as cancer. She and her team have been focusing their sights on a protein they discovered in this way; promising lab tests indicate that blocking this protein might slow the progression of some cancers.

    Her findings place this research in the new field of “cancer metabolism,” which seeks to understand how the aberrant, or uncontrolled metabolic processes in cancers might turned against them to stop their growth.

    She and her team studied cells from children suffering from an extremely rare disease, citrullinemia type II, who are missing the gene for a protein called citrin. Clinically, children with this disease tend to be smaller than average, and to avoid candy. Her research revealed that this protein normally helps keep the body supplied with an amino acid called aspartate which is required to produce DNA and RNA in addition to the breakdown of glucose; so deficiency in this protein causes the cells to divide less.

    Research into another genetic childhood disease, citrullinemia type I, had already given the team the lens they needed to understand how cancer cells rely on aspartate to divide and migrate. Children born with this disease are missing a gene called ASS1; the lack of ASS1 connects the disease to particularly aggressive, hard-to-treat cancers in which this gene tends to be silenced or mutated. Since this gene also requires aspartate to function, Erez and her team surmised that the silencing had less to do with the gene’s function and more with competition for aspartate and the cancer cells’ craving for ever more of this amino acid to help them divide and spread. Interestingly, the dependence on citrin for aspartate supplementation is seen in cancers both with and without ASS1 expression.

    Ayelet and her team realized that citrin – the protein that helps regulate childhood growth – could present a possible target for anticancer therapies. Blocking this protein would hopefully disrupt the cancer’s overactive metabolic cycle, diminish the cancer cells’ aspartate supply and slow their growth, thus making them less aggressive, less likely to spread and possibly more treatable with other, conventional means. To that end, Erez and her group have been developing a molecule to block citrin, and testing it in the lab. Yeda Research and Development Co., Ltd., the technology transfer arm of the Weizmann Institute of Science, is working with Erez to advance her research to the point that it can be developed for biomedical application.

    Dr. Ayelet Erez’s research is supported by the Moross Integrated Cancer Center; the Irving B. Harris Fund; the Adelis Foundation; the Rising Tide Foundation; the Comisaroff Family Trust; and the European Research Council. Dr. Erez is the incumbent of the Leah Omenn Career Development Chair.

    See the full article here .

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 12:27 pm on May 20, 2017 Permalink | Reply
    Tags: Antibody for fighting cancer emerges, , Cancer, , LAP+ cells are increased in human cancer and predict a poor prognosis, , , T cells   

    From MedicalXpress: “Antibody for fighting cancer emerges” 

    Medicalxpress bloc

    MedicalXpress

    1

    Brigham and Women’s Hospital

    May 19, 2017
    No writer credit found

    1
    Killer T cells surround a cancer cell. Credit: NIH

    While studying the underpinnings of multiple sclerosis, investigators at Brigham and Women’s Hospital came across important clues for how to treat a very different disease: cancer. In a paper published in Science Immunology, a group of researchers led by neurologist Howard Weiner, MD, describe an antibody that can precisely target regulatory T cells which in turn unleashes the immune system to kill cancer cells. The team reports that the antibody decreased tumor growth in models of melanoma, glioblastoma and colorectal carcinoma, making it an attractive candidate for cancer immunotherapy.

    “As a neurologist, I never expected I would be publishing a paper about cancer immunotherapy, but as my team studied a subpopulation of T cells that are supposed to prevent autoimmune disease, we had an idea: if cancer is the opposite of an autoimmune disease, we could turn our investigations around and think about how to restore the immune system’s ability to prevent cancer’s growth,” said Weiner, co-director the Ann Romney Center for Neurologic Diseases at BWH.v

    The Weiner lab has been studying regulatory T cells (Tregs) for many years. Tregs, which help maintain the immune system’s tolerance of “self,” can, inadvertently, promote cancer’s growth by preventing the body’s immune system from detecting and attacking cancer cells. The researchers found that they could precisely target Tregs using an antibody that locks in on a molecular complex that’s uniquely expressed on the cell surface of Tregs. The team developed these so-called anti-LAP antibodies initially to investigate the development of multiple sclerosis, but realized their work had implications for the study of cancer.

    Previous studies have shown that LAP+ cells are increased in human cancer and predict a poor prognosis. Being able to target these cells could offer a new way to treat the disease.

    In the current study, the team used preclinical models to investigate how well anti-LAP antibodies could work in blocking the essential mechanisms of Tregs and restoring the immune system’s ability to fight cancer. They found that anti-LAP acts on multiple cell populations to promote the immune system’s ability to fight cancer, including increasing the activity of certain types of T cells and enhancing immune memory.

    “In addition to studying its therapeutic effect, we wanted to characterize the mechanism by which the anti-LAP antibody can activate the immune system,” said lead author Galina Gabriely, PhD, a scientist in the Weiner laboratory. “We found that it affects multiple arms of the immune system.”

    The current study has been conducted in preclinical models of cancer. In order to move this work toward the clinic, Tilos Therapeutics will be expanding on the Weiner lab’s research to modify the antibody for use in humans, a process that usually takes several years.

    “I see this work as the perfect example of how research in all branches of immunology into the mechanistic underpinnings of disease can have a huge impact on other fields, such as oncology,” said Barbara Fox, PhD, CEO of Tilos Therapeutics.

    See the full article here .

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    Medical Xpress is a web-based medical and health news service that is part of the renowned Science X network. Medical Xpress features the most comprehensive coverage in medical research and health news in the fields of neuroscience, cardiology, cancer, HIV/AIDS, psychology, psychiatry, dentistry, genetics, diseases and conditions, medications and more.

     
  • richardmitnick 8:19 pm on May 16, 2017 Permalink | Reply
    Tags: , Cancer, , ,   

    From Help Fight Childhood Cancer at WCG: “Help Fight Childhood Cancer Project Researchers Publish a Paper” 

    New WCG Logo

    WCGLarge

    World Community Grid (WCG)

    6 Jun 2016
    Represented 5.16.17

    Summary
    The Help Fight Childhood Cancer project searched for a cure for a particular childhood cancer. The researchers have found that some of the promising compounds they identified also show an antidepressant capability.

    Lay Summary:

    The Help Fight Childhood Cancer project researchers have published a paper on serendipitous results they found from the drug candidate search run on World Community Grid. The project originally searched for candidate compounds that targeted specific proteins to help cure a childhood brain cancer called neuroblastoma. Some of the targeted proteins are also involved in several psychological disorders. They have found that some of the identified compounds show an antidepressant capability. Furthermore, additional research might lead to potential treatments for Huntington’s disease and Alzheimer’s disease. The paper was published in the journal Neurochemistry International.

    Paper title: Effects of novel small compounds targeting TrkB on neuronal cell survival and depression-like behavior

    Authors: Mayu Fukuda, Atsushi Takotori, Yohko Nakamura, Akiko Suganami, Tyuji Hoshino, Yutaka Tamura, Akira Nakagawara

    Technical Abstract:

    Brain-derived neurotrophic factor (BDNF) and its high affinity receptor tyrosine kinase receptor B (TrkB) are involved in neuronal survival, maintenance, differentiation and synaptic plasticity. Deficiency of BDNF was reported to be associated with psychological disorders such as depression. Hence we examined proliferative effect of 11 candidate TrkB agonistic compounds in TrkB-expressing SH-SY5Y cells, via a hypothesis that some candidate compounds identified in our previous in silico screening for a small molecule targeting the BDNF binding domain of TrkB should activate TrkB signaling. In the present study, two promising compounds, 48 and 56, were identified and subsequently assessed for their ability to induce TrkB phosphorylation in vitro and in vivo. Likewise those seen in BDNF, the compounds mediated TrkB phosphorylation was blocked by the Trk inhibitor, K252a. Since BDNF-TrkB signaling deficiency is associated with the pathogenesis of depression and reactivation of this signaling by antidepressants is a cause of the pathogenic state recovery, the compounds were subjected to the assessment for forced swim test, which is a mouse model of depression. We found that compound 48 significantly reduced mouse immobility time compared with the control vehicle injection, suggesting the confirmation of hypothetical antidepressant-like efficacy of 48 compound in vivo. Thus, our present study demonstrated that compound 48, selected through in silico screening, is a novel activator of TrkB signaling and a potential antidepressant molecule.

    Click here to see the paper’s abstract online.

    See the full article here.

    Ways to access the blog:
    https://sciencesprings.wordpress.com
    http://facebook.com/sciencesprings

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    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”
    WCG projects run on BOINC software from UC Berkeley.
    BOINCLarge

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    My BOINC
    MyBOINC
    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    faah-1-new-screen-saver

    faah-1-new

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
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  • richardmitnick 12:59 pm on May 13, 2017 Permalink | Reply
    Tags: , Cancer, ,   

    From Hopkins: “New study sheds light on why cancer often strikes those with healthy lifestyles” 

    Johns Hopkins
    Johns Hopkins University

    Mar 23, 2017
    Vanessa Wasta

    1
    Yellow breast cancer cell on a red background. Wikimedia Commons

    A new study by scientists at Johns Hopkins provides evidence that random, unpredictable DNA copying “mistakes” account for nearly two-thirds of the mutations that cause cancer.

    The researchers say their conclusions are supported by epidemiologic studies showing that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles. But among the factors driving the new study, they add, is that cancer often strikes people who follow all the rules of healthy living—nonsmoker, healthy diet, healthy weight, little or no exposure to known carcinogens—and have no family history of the disease, prompting the pained question, “Why me?”

    “It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer. But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,” says Cristian Tomasetti, assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. “These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

    Adds Bert Vogelstein, co-director of the Ludwig Center at the Kimmel Cancer Center: “We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations. However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed,”

    Tomasetti and Vogelstein’s research will be published Friday [3.23.17] in the journal Science.

    Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S and abroad. But they say the new study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.

    “These cancers will occur no matter how perfect the environment,” Vogelstein says.

    Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S and abroad. But they say the new study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.

    “These cancers will occur no matter how perfect the environment,” Vogelstein says.

    In a previous study authored by Tomasetti and Vogelstein in the Jan. 2, 2015, issue of Science, the pair reported that DNA copying errors could explain why certain cancers in the U.S., such as those of the colon, occur more commonly than other cancers, such as brain cancer.

    In the new study, the researchers addressed a different question: What fraction of mutations in cancer are due to these DNA copying errors?

    To answer this question, the scientists took a close look at the mutations that drive abnormal cell growth among 32 cancer types. They developed a new mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

    According to the researchers, it generally takes two or more critical gene mutations for cancer to occur. In a person, these mutations can be due to random DNA copying errors, the environment, or inherited genes. Knowing this, Tomasetti and Vogelstein used their mathematical model to show, for example, that when critical mutations in pancreatic cancers are added together, 77 percent of them are due to random DNA copying errors, 18 percent to environmental factors (such as smoking), and the remaining 5 percent to heredity.

    In other cancer types, such as those of the prostate, brain, or bone, more than 95 percent of the mutations are due to random copying errors.

    Lung cancer, they note, presents a different picture: 65 percent of all the mutations are due to environmental factors, mostly smoking, and 35 percent are due to DNA copying errors. Inherited factors are not known to play a role in lung cancers.

    Looking across all 32 cancer types studied, the researchers estimate that 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors, and the remaining 5 percent are inherited.

    The scientists say their approach is akin to attempts to sort out why “typos” occur when typing a 20-volume book: being tired while typing, which represents environmental exposures; a stuck or missing key in the keyboard, which represent inherited factors; and other typographical errors that randomly occur, which represent DNA copying errors.

    “You can reduce your chance of typographical errors by making sure you’re not drowsy while typing and that your keyboard isn’t missing some keys,” Vogelstein says. “But typos will still occur, because no one can type perfectly. Similarly, mutations will occur, no matter what your environment is, but you can take steps to minimize those mutations by limiting your exposure to hazardous substances and unhealthy lifestyles.”

    Tomasetti and Vogelstein’s 2015 study created vigorous debate from scientists who argued that their previously published analysis did not include breast or prostate cancers, and it reflected only cancer incidence in the United States.

    Tomasetti and Vogelstein now report a similar pattern worldwide, however, supporting their conclusions. They reasoned that the more cells divide, the higher the potential for so-called copying mistakes in the DNA of cells in an organ. They compared total numbers of stem cell divisions with cancer incidence data collected by the International Agency for Research on Cancer on 423 registries of cancer patients from 68 countries other than the United States, representing 4.8 billion people, or more than half of the world’s population. This time, the researchers were also able to include data from breast and prostate cancers. They found a strong correlation between cancer incidence and normal cell divisions among 17 cancer types, regardless of the countries’ environment or stage of economic development.

    Tomasetti says these random DNA copying errors will only get more important as societies face aging populations, prolonging the opportunity for our cells to make more and more DNA copying errors. And because these errors contribute to a large fraction of cancer, Vogelstein says that people with cancer who have avoided known risk factors should be comforted by their findings.

    “It’s not your fault,” says Vogelstein. “Nothing you did or didn’t do was responsible for your illness.”

    In addition to Tomasetti and Vogelstein, Lu Li, a doctoral student in Tomasetti’s laboratory in the Department of Biostatistics at the Johns Hopkins Bloomberg School of Public Health, also contributed to the research.

    See the full article here .

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    Johns Hopkins Campus

    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

    See the full article here .

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  • richardmitnick 11:01 am on May 13, 2017 Permalink | Reply
    Tags: , Cancer, , ,   

    From ICL: “A lead candidate for immunotherapy may increase tumour growth in certain cancers” 

    Imperial College London
    Imperial College London

    12 May 2017
    Hayley Dunning

    1
    Boosting a part of the immune system known to have anti-tumour properties may actually help tumours grow in cancers linked to chronic inflammation. No image credit.

    Cancer immunotherapies boost aspects of the body’s normal immune system, to help fight tumours. They are part of a fast-evolving field of research and medicine, with several types of immunotherapies currently in clinical trials.

    Now, a research team at Imperial College London has found that in a mouse model developing liver cancer, one immunoreceptor – attractive candidate for immunotherapies – promoted rather than delayed tumour growth.

    The researchers believe this could have implications for the effectiveness of immunotherapy in combating human cancers caused by inflammation, such as some liver and colon cancers. The study, funded by the Wellcome, Trust was published in Nature Communications earlier this year.

    Lead author Dr Nadia Guerra from the Department of Life Sciences at Imperial, said: “Immunotherapies have shown unprecedented successes in treating cancer patients with advanced forms of cancer, especially metastatic melanomas. These therapies are now being tested in various type of cancer and novel combination approaches are being developed at a very fast pace.

    “Nonetheless, there are still challenges ahead to optimise those therapies and reduce adverse effects. Scientists and clinicians are working at identifying cancer patients that would benefit the most from those therapies to increase success rates and hopefully achieve complete remission.”

    How immunotherapies tackle cancer

    The part of the immune system involved in the study is called NKG2D (Natural Killer Group 2 member D). NKG2D is a type of immunoreceptor – a molecule present on the surface of the body’s immune cells that recognises signals from normal cells that are distressed.

    For example, if a normal cell is infected with a virus, it will display molecules on its surface that the NKG2D immunoreceptor can detect. The immune cell then directs a lethal hit that destroys the infected cell.

    Dr Guerra first showed ten years ago that this mechanism also works against cancerous tumours – demonstrated by the fact that tumours grew faster in mice that had their NKG2D activity supressed.

    However, NKG2D contributes to inflammation and has been found to play a role in chronic inflammatory disorders, such as Crohn’s disease. In this case, the NKG2D misfires and attacks normal cells instead of damaged ones.

    The paradoxical effect of inflammation

    The team looked into whether NKG2D’s roles in chronic inflammation and cancer could help tumours to grow in these types of cancer.

    To do this, they used a mouse model of liver cancer driven by inflammation. Human and mouse NKG2D receptors are very similar, so the results are thought to be relevant to human liver cancers.

    They found that the tumours actually grew faster in mice with functional NKG2D than in mice that lacked NKG2D. Dr Guerra said: “NKG2D is a potent anti-tumour agent, but we have found that it might actually have the opposite effect in tumours that arise and/or grow from a background of chronic inflammation.”

    In these environments, the liver tissue undergoes cycles of damage and repair continuously as it is fought by NKG2D, making the cells more at risk of developing genetic mutations.

    Dr Guerra said: “The paradoxical effect of NKG2D we discovered exposes the need to selectively target the types of cancer that will benefit from NKG2D-based immunotherapy. What is beneficial in fighting one type of cancer might have the opposite effect in another.

    “We need to be more precise when administering a chosen therapy to a particular type of cancer. Our data unravels a conceptual shift that will inform which cancer these new therapies can benefit the most, and help match the best therapy to each patient.”

    See the full article here .

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    Imperial College London

    Imperial College London is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialisation, harnessing science and innovation to tackle global challenges.

     
  • richardmitnick 6:25 am on March 27, 2017 Permalink | Reply
    Tags: "Cancer Biology Reproducibility Project Sees Mixed Results" Read it and Weep, , Cancer, Cancer Biology Reproducibility Project Sees Mixed Results, ,   

    From NOVA: “Cancer Biology Reproducibility Project Sees Mixed Results” Read it and Weep 

    PBS NOVA

    NOVA

    18 Jan 2017 [Don’t know how I missed this, or maybe they never put it up in social media before?]
    Courtney Humphries

    How trustworthy are the findings from scientific studies?

    A growing chorus of researchers says there’s a “reproducibility crisis” in science, with too many discoveries published that may be flukes or exaggerations. Now, an ambitious project to test the reproducibility of top studies in cancer research by independent laboratories has published its first five studies in the open-access journal eLife.

    “These are the first public replication studies conducted in biomedical science, and that in itself is a huge achievement,” says Elizabeth Iorns, CEO of Science Exchange and one of the project’s leaders.

    1
    Cancer biology is just one of many fields being scrutinized for the reproducibility of its studies.

    The Reproducibility Project: Cancer Biology is a collaboration between the non-profit Center for Open Science and the for-profit Science Exchange, which runs a network of laboratories for outsourcing biomedical research. It began in 2013 with the goal of repeating experiments from top-cited cancer papers; all of the work has been planned, executed, and published in the open, in consultation with the studies’ original authors. These papers are the first of many underway and slated to be published in the coming months.

    The outcome so far has been mixed, the project leaders say. While some results are similar, none of the studies looks exactly like the original, says Tim Errington, the project’s manager. “They’re all different in some way. They’re all different in different ways.” In some studies, the experimental system didn’t behave the same. In others, the result was slightly different, or it did not hold up under the statistical scrutiny project leaders used to analyze results. All in all, project leaders report, one study failed to reproduce the original finding, two supported key aspects of the original papers, and two were inconclusive because of technical issues.

    Errington says the goal is not to single out any individual study as replicable or not. “Our intent with this project is to perform these direct replications so that we can understand collectively how reproducible our research is,” he says.

    Indeed, there are no agreed-upon criteria for judging whether a replication is successful. At the project’s end, he says, the team will analyze the replication studies collectively by several different standards—including simply asking scientists what they think. “We’re not going to force an agreement—we’re trying to create a discussion,” he says.

    The project has been controversial; some cancer biologists say it’s designed to make them look bad bad at a time when federal research funding is under threat. Others have praised it for tackling a system that rewards shoddy research. If the first papers are any indication, those arguments won’t be easily settled. So far, the studies provide a window into the challenges of redoing complex laboratory studies. They also underscore the need that, if cancer biologists want to improve the reproducibility of their research, they have to agree on a definition of success.

    An Epidemic?

    A recent survey in Nature of more than 1,500 researchers found that 70% have tried and failed to reproduce others’ experiments, and that half have failed to reproduce their own. But you wouldn’t know it by reading published studies. Academic scientists are under pressure to publish new findings, not replicate old research. There’s little funding earmarked toward repeating studies, and journals favor publishing novel discoveries. Science relies on a gradual accumulation of studies that test hypotheses in new ways. If one lab makes a discovery using cell lines, for instance, the same lab or another lab might investigate the phenomenon in mice. In this way, one study extends and builds on what came before.

    For many researchers, that approach—called conceptual replication, which gives supporting evidence for a previous study’s conclusion using another model—is enough. But a growing number of scientists have been advocating for repeating influential studies. Such direct replications, Errington says, “will allow us to understand how reliable each piece of evidence we have is.” Replications could improve the efficiency of future research by winnowing out false hypotheses early and help scientists recreate others’ work in order to build on it.

    In the field of cancer research, some of the pressure to improve reproducibility has come from the pharmaceutical industry, where investing in a spurious hypothesis or therapy can threaten profits. In a 2012 commentary in Nature, cancer scientists Glenn Begley and Lee Ellis wrote that they had tried to reproduce 53 high-profile cancer studies while working at the pharmaceutical company Amgen, and succeeded with just six. A year earlier, scientists at Bayer HealthCare announced that they could replicate only 20–25% of 47 cancer studies. But confidentiality rules prevented both teams from sharing data from those attempts, making it difficult for the larger scientific community to assess their results.

    ‘No Easy Task’

    Enter the Reproducibility Project: Cancer Biology. It was launched with a $1.3 million grant from the Laura and John Arnold Foundation to redo key experiments from 50 landmark cancer papers from 2010 to 2012. The work is carried out in the laboratory network of Science Exchange, a Palo Alto-based startup, and the results tracked and made available through a data-sharing platform developed by the Center for Open Science. Statisticians help design the experiments to yield rigorous results. The protocols of each experiment have been peer-reviewed and published separately as a registered report beforehand, which advocates say prevents scientists from manipulating the experiment or changing their hypothesis midstream.

    The group has made painstaking efforts to redo experiments with the same methods and materials, reaching out to original laboratories for advice, data, and resources. The labs that originally wrote the studies have had to assemble information from years-old research. Studies have been delayed because of legal agreements for transferring materials from one lab to another. Faced with financial and time constraints, the team has scaled back its project; so far 29 studies have been registered, and Errington says the plan is to do as much as they can over the next year and issue a final paper.

    “This is no easy task, and what they’ve done is just wonderful,” says Begley, who is now chief scientific officer at Akriveia Therapeutics and was originally on the advisory board for the project but resigned because of time constraints. His overall impression of the studies is that they largely flunked replication, even though some data from individual experiments matched. He says that for a study to be valuable, the major conclusion should be reproduced, not just one or two components of the study. This would demonstrate that the findings are a good foundation for future work. “It’s adding evidence that there’s a challenge in the scientific community we have to address,” he says.

    Begley has argued that early-stage cancer research in academic labs should follow methods that clinical trials use, like randomizing subjects and blinding investigators as to which ones are getting a treatment or not, using large numbers of test subjects, and testing positive and negative controls. He says that when he read the original papers under consideration for replication, he assumed they would fail because they didn’t follow these methods, even though they are top papers in the field.. “This is a systemic problem; it’s not one or two labs that are behaving badly,” he says.

    Details Matter

    For the researchers whose work is being scrutinized, the details of each study matter. Although the project leaders insist they are not designing the project to judge individual findings—that would require devoting more resources to each study—cancer researchers have expressed concern that the project might unfairly cast doubt on their discoveries. The responses of some of those scientists so far raise issues about how replication studies should be carried out and analyzed.

    One study, for instance, replicated a 2010 paper led by Erkki Ruoslahti, a cancer researcher at Sanford Burnham Prebys Medical Discovery Institute in San Diego, which identified a peptide that could stick to and penetrate tumors. Ruoslahti points to a list of subsequent studies by his lab and others that support the finding and suggest that the peptide could help deliver cancer drugs to tumors. But the replication study found that the peptide did not make tumors more permeable to drugs in mice. Ruoslahti says there could be a technical reason for the problem, but the replication team didn’t try to troubleshoot it. He’s now working to finish preclinical studies and secure funding to move the treatment into human trials through a company called Drugcendr. He worries that replication studies that fail without fully exploring why could derail efforts to develop treatments. “This has real implications to what will happen to patients,” he says.

    Atul Butte, a computational biologist at the University of California San Francisco, who led one of the original studies that was reproduced, praises the diligence of the team. “I think what they did is unbelievably disciplined,” he says. But like some other scientists, he’s puzzled by the way the team analyzed results, which can make a finding that subjectively seems correct appear as if it failed. His original study used a data-crunching model to sort through open-access genetic information and identify potential new uses for existing drugs. Their model predicted that the antiulcer medication cimetidine would have an effect against lung cancer, and his team validated the model by testing the drug against lung cancer tumors in mice. The replication found very similar effects. “It’s unbelievable how well it reproduces our study,” Butte says. But the replication team used a statistical technique to analyze the results that found them not statistically significant. Butte says it’s odd that the project went to such trouble to reproduce experiments exactly, only to alter the way the results are interpreted.

    Errington and Iorns acknowledge that such a statistical analysis is not common in biological research, but they say it’s part of the group’s effort to be rigorous. “The way we analyzed the result is correct statistically, and that may be different from what the standards are in the field, but they’re what people should aspire to,” Iorns says.

    In some cases, results were complicated by inconsistent experimental systems. One study tested a type of experimental drug called a BET inhibitor against multiple myeloma in mice. The replication found that the drug improved the survival of diseased mice compared to controls, consistent with the original study. But the disease developed differently in the replication study, and statistical analysis of the tumor growth did not yield a significant finding. Constantine Mitsiades, the study’s lead author and a cancer researcher at the Dana-Farber Cancer Institute, says that despite the statistical analysis, the replication study’s data “are highly supportive of and consistent with our original study and with subsequent studies that also confirmed it.”

    A Fundamental Debate

    These papers will undoubtedly provoke debate about what the standards of replication should be. Mitsiades and other scientists say that complex biological systems like tumors are inherently variable, so it’s not surprising if replication studies don’t exactly match their originals. Inflexible study protocols and rigid statistics may not be appropriate for evaluating such systems—or needed.

    Some scientists doubt the need to perform copycat studies at all. “I think science is self-correcting,” Ruoslahti says. “Yes, there’s some loss of time and money, but that’s just part of the process.” He says that, on the positive side, this project might encourage scientists to be more careful, but he also worries that it might discourage them from publishing new discoveries.

    Though the researchers who led these studies are, not surprisingly, focused on the correctness of the findings, Errington says that the variability of experimental models and protocols is important to document. Advocates for replication say that current published research reflects an edited version of what happened in the lab. That’s why the Reproducibility Project has made a point to publish all of its raw data and include experiments that seemed to go awry, when most researchers would troubleshoot them and try again.

    “The reason to repeat experiments is to get a handle on the intrinsic variability that happens from experiment to experiment,” Begley says. With a better understanding of biology’s true messiness, replication advocates say, scientists might have a clearer sense of whether or not to put credence in a single study. And if more scientists published the full data from every experiment, those original results may look less flashy to begin with, leading fewer labs to chase over-hyped hypotheses and therapies that never pan out. An ultimate goal of the project is to identify factors that make it easier to produce replicable research, like publishing detailed protocols and validating that materials used in a study, such as antibodies, are working properly.


    Access mp4 video here .

    Beyond this project, the scientific community is already taking steps to address reproducibility. Many scientific journals are making stricter requirements for studies and publishing registered reports of studies before they’re carried out. The National Institutes of Health has launched training and funding initiatives to promote robust and reproducible research. F1000Research, an open-access, online publisher launched a Preclinical Reproducibility and Robustness Channel in 2016 for researchers to publish results from replication studies. Last week several scientists published a reproducibility manifesto in the journal Human Behavior that lays out a broad series of steps to improve the reliability of research findings, from the way studies are planned to the way scientists are trained and promoted.

    See the full article here .

    Please help promote STEM in your local schools.

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    Stem Education Coalition

    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

     
  • richardmitnick 9:23 am on March 8, 2017 Permalink | Reply
    Tags: , , Cancer, cure cancer, , , Push button,   

    From Paulson: Women in STEM – “Push button, cure cancer” Ph.D. candidates Nabiha Saklayen and Marinna Madrid 

    Harvard School of Engineering and Applied Sciences
    John A Paulson School of Engineering and Applied Sciences

    March 7, 2017
    Adam Zewe

    Two Harvard graduate students want to make curing blood cancer or HIV as easy as pressing a button.

    2
    Saklayen and Madrid are excited to move forward with their startup, Cellino. (Photo by Adam Zewe/SEAS Communications)

    1
    Cellino is a spinoff of the nanotechnology research being conducted in the Mazur lab. (Photo by Adam Zewe/SEAS Communications)

    Ph.D. candidates Nabiha Saklayen and Marinna Madrid have launched a startup to develop a simple, push-button device clinicians could use for gene therapy treatments. Their enterprise, Cellino, hopes to commercialize technology being developed in the lab of Eric Mazur, Balkanski Professor of Physics and Applied Physics at the John A. Paulson School of Engineering and Applied Sciences.

    The early-stage laboratory spinoff, which the pair launched in November, claimed first prize in the International Society for Optics and Photonics (SPIE) Startup Challenge, a pitch-off contest between more than 40 startups from around the world. In addition to winning $10,000 cash and $5,000 in optics products, Saklayen and Madrid were lauded for the impressive business potential of their startup.

    Their technique uses laser-activated nanostructures to deliver gene therapies directly into cells. When a laser is shined onto the nanostructures, the intense hot spots can open transient pores in nearby cells, Saklayen explained.

    “These pores are open long enough for any cargo that is around in the surrounding liquid to diffuse into the cell, and then the pores seal,” she said. “It is sort of like a magical opening where we can deliver molecules into the cell without damaging it, in a very targeted, quick way.”

    Developing effective intracellular delivery methods is a problem that has plagued biologists for decades, partly because the plasma membrane that surrounds a cell is selectively permeable and bars most molecules from entering.

    “Biologists have tried a number of different methods to do this, including viruses and chemical and physical processes, but none of them have been consistent enough and safe enough to be used reliably in treatments for blood disease,” said Madrid.

    The reliability of the nanostructure method developed at SEAS would give it a leg up over current practices. The biggest hurdle Madrid and Saklayen face now is translating the Mazur lab’s technology into a scalable, turnkey device.

    Their goal is to package the technology into a shoebox-sized device that contains everything a user needs—the laser, substrates, optical components, and computer interface. A user would put a patient’s cells and the nanofabricated chips into the device and use a touch screen to treat the cells, which could then be implanted into the patient.

    According to the Cellino team, those cells could be used to treat a number of different blood diseases, including HIV and blood cancers. By delivering gene-editing molecules into a patient’s hematopoietic stem cells, for instance, a clinician could repopulate a patient’s bone marrow with HIV-resistant cells. To treat cancers that affect the blood, the technology could be used to weaponize a patient’s T-cells, and then return them to the blood stream to attack the cancer.

    “What I find really exciting about this project is it is really pushing the barriers of what is the norm,” Saklayen said. “People talk about curing blood cancer all the time, but we have this unique opportunity to really enable that. That is the most inspiring part—we have an opportunity to make a difference in people’s lives. That is what drives me everyday to keep working hard.”

    As they move forward with Cellino, Saklayen and Madrid are working closely with Harvard’s Office of Technology Development (OTD), which has filed patent applications to secure the lab’s intellectual property and develop a viable commercialization strategy for the technology. Alan Gordon, a Director of Business Development in OTD, has been advising the team on how to develop a business plan and launch the company.

    After graduating from the Ph.D. program this spring, Saklayen will pursue Cellino full time. Madrid plans to graduate early so she can soon focus solely on the company, too. The co-founders have applied to a number of startup incubators and plan to enter additional pitch competitions to gain more validation for both their technology and their business plan.

    “There is definitely a production challenge when you talk about making things at a larger scale, but we are making good progress,” Madrid said. “The technology is very powerful because it is so streamlined. Now it is all about packaging.”

    Mazur is proud of his students’ accomplishments and excited for the potential of their startup. “This work is really transformative and opens the door to new therapies for currently incurable diseases,” he said.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Through research and scholarship, the Harvard School of Engineering and Applied Sciences (SEAS) will create collaborative bridges across Harvard and educate the next generation of global leaders. By harnessing the power of engineering and applied sciences we will address the greatest challenges facing our society.

    Specifically, that means that SEAS will provide to all Harvard College students an introduction to and familiarity with engineering and technology as this is essential knowledge in the 21st century.

    Moreover, our concentrators will be immersed in the liberal arts environment and be able to understand the societal context for their problem solving, capable of working seamlessly withothers, including those in the arts, the sciences, and the professional schools. They will focus on the fundamental engineering and applied science disciplines for the 21st century; as we will not teach legacy 20th century engineering disciplines.

    Instead, our curriculum will be rigorous but inviting to students, and be infused with active learning, interdisciplinary research, entrepreneurship and engineering design experiences. For our concentrators and graduate students, we will educate “T-shaped” individuals – with depth in one discipline but capable of working seamlessly with others, including arts, humanities, natural science and social science.

    To address current and future societal challenges, knowledge from fundamental science, art, and the humanities must all be linked through the application of engineering principles with the professions of law, medicine, public policy, design and business practice.

    In other words, solving important issues requires a multidisciplinary approach.

    With the combined strengths of SEAS, the Faculty of Arts and Sciences, and the professional schools, Harvard is ideally positioned to both broadly educate the next generation of leaders who understand the complexities of technology and society and to use its intellectual resources and innovative thinking to meet the challenges of the 21st century.

    Ultimately, we will provide to our graduates a rigorous quantitative liberal arts education that is an excellent launching point for any career and profession.

     
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