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  • richardmitnick 4:51 pm on October 27, 2014 Permalink | Reply
    Tags: , Cancer, , , ,   

    From Mapping Cancer Markers at WCG: “Early-stage results from the Mapping Cancer Markers team” 

    New WCG Logo

    27 Oct 2014
    The Mapping Cancer Markers research team

    The Princess Margaret Cancer Foundation Mapping Cancer Markers team has nearly finished establishing their benchmarks – a crucial step for their research and other related medical research around the world. See their in-depth update for the latest news about their efforts to help predict, identify and treat cancer.

    Summary
    Thanks to your help, the Mapping Cancer Markers team is nearly finished with benchmarking their first set of genetic markers. In this update, the team presents an in-depth review of what they’ve accomplished thus far, and what significance this early work will have for cancer research at their lab and elsewhere.

    The Mapping Cancer Markers (MCM) team would like to extend a huge thank you to World Community Grid members everywhere. As of October 27, 2014, we have surpassed 89,000 years of computation, a goal that simply would not be possible without your help.

    We are happy to report that we have begun to analyze the results using a high-throughput analytics package to assess the fitness and landscape of gene signature sizes between 5 and 25 genes. This analysis has shown that smaller signatures usually comprise different genes compared to larger signatures (i.e., you cannot “build” a larger signature from small ones), and that those genes are targeting many different signaling cascades and biological processes.

    Analytics

    To get a better understanding of how much data our team is receiving, we’d like to briefly introduce one of the tools that we have adopted to analyze the incoming results. From the very beginning of the project, it was clear that analyzing such a large, ongoing flow of data would be a challenge. Thus, we started to use the IBM® InfoSphere® Streams real-time analytics platform to streamline the analysis pipeline. When complete, our Streams application will run continuously, processing members’ work units in real time as we receive them. We currently have the core analysis framework implemented and running on a subset of the MCM results. We will continue to add additional layers of analysis, and fine-tune our system until it is running at full capacity. For that reason, we have dedicated one of our main compute servers (IBM Power® 780) to analyzing MCM results.

    Results

    Pictured below is a sampling (a very small fraction) of some of the ongoing work that will establish a benchmark for further experiments. Each dot in both of the graphs is a potential lung-cancer biomarker. These graphics are distilled from thousands of MCM results sent back by World Community Grid members.

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    Most of the dots have very little significance; this is expected because not everything shuts down or is activated in cancer. In other words, the graphics show differences between the disease state and the non-disease state, so we expect some things to be different, but not everything. For those reasons, most biomarkers cannot significantly differentiate cancer from non-cancer samples – this is represented by the haze of dots along the zero line. We show two graphs to illustrate the difference between shorter and longer gene signatures. Some genes that are more predictive in the shorter signature sizes do not necessarily hold their predictive power when considering more genes per signature. Most importantly, in each analysis, a few biomarkers frequently appear in high-scoring signatures. Our analysis wades through massive amounts of data to recognize those few markers that stand out.

    The first half of the “benchmarking” experiment involves determining the performance of markers as the size of the signature changes. For instance, when we compare successful 5-marker signatures against 20-marker signatures, which markers are consistently useful? Which ones increase or diminish in predictive power? Is there an optimum size for signatures? And most importantly, can we identify seemingly minor players that are critical, but not yet in clinical use that can discriminate between normal and disease states?

    graph

    After surveying the first several billion signatures, we have identified the highest-ranking combinations and underlying single genes. After separating those genes by signature size, we can see how some genes remain important regardless of the size, and how other genes “appear” to be important but are only showing up as single events. Considering we have not yet analyzed the complete data set, we have identified the genes by their known functions rather than names, to eliminate any bias towards known markers. However, even by their functions, we can see that many important signaling cascades and biological processes are affected. The most notable of these is “Cellular Fate and Organization”, which makes sense. Sometimes, when an organism loses the ability to naturally kill defective cells, it leads to uncontrolled growth, one of the hallmarks of cancer.

    Network Analysis of Major Genes:

    To further analyze the nature of our top-performing genes, we can identify their inter-relations in biological networks. We currently maintain one of the largest curated protein-protein interaction databases, which enables us to determine whether our genes (when converted to proteins) are known to interact with other important biomarkers, and in turn, what biological processes may be involved. The graph below shows one such network; nodes in the graph represent genes, edges are physical protein interactions. Node color highlights biological function as described in the legend. Use of biological networks can reveal very small subtleties of how the mechanisms of disease function and elucidate how our proteins may be causing problems; thus, eventually leading to understanding how cancer starts, progresses and how can we treat it.

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    In the above network, 20 out of 24 important proteins we have identified on World Community Grid (right hand side) can be linked through known protein interactions and 56 other proteins (left hand side). We have also conducted a short analysis of the 4 proteins not yet identified using a software prediction package and found those to have significant partners. Those interactions will be evaluated in the near future. The 20 proteins noted above, strikingly, do not interact directly, however, 4 of them show very high interactivity, and can be considered as hubs. From other analyses we know that “hub proteins” are often critical, as they affect many signaling cascades and biological processes. When such proteins malfunction, catastrophic changes often result. On the other hand, proteins with low interactivity could be useful as clinical biomarkers. If they are known to only interact with a few other proteins, then their activity may help to identify particular states of cancer, while having less background “noise”. As a whole we can see that for the most part, our genes of interest are targeting mostly “genome maintenance” and “cellular fate and organization” proteins, which make up about 70% of the interacting proteins (left hand side). This is a good indication that most of the pathways affected are in those major categories, which is consistent with how we understand lung cancer to progress.

    Funding & Fundraising:

    This past August, we completed our 4th successful Team Ian Ride for Cancer Informatics Research. We were able to raise over $80,000 for cancer research in the name of a former Jurisica student, Ian Van Toch.

    Part of this funding is used for the best student paper award at the ISMB conference, and for supporting Cancer Informatics interns.

    We also support a special seminar series at Princess Margaret Cancer Center, and the recent presentation by Dr. Wan Lam from BC Cancer Agency discussed “Multi-dimensional Analysis of Lung Cancer Genomes”.

    See the full article here.

    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.

    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.

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BETCHA!!

    “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-

    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

    World Community Grid is a social initiative of IBM Corporation
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  • richardmitnick 9:04 pm on October 16, 2014 Permalink | Reply
    Tags: , , Cancer, ,   

    From LLNL: “Lab, UC Davis partner to personalize cancer medications” 


    Lawrence Livermore National Laboratory

    10/16/2014
    Stephen P Wampler, LLNL, (925) 423-3107, wampler1@llnl.gov

    Buoyed by several dramatic advances, Lawrence Livermore National Laboratory scientists think they can tackle biological science in a way that couldn’t be done before.

    Over the past two years, Lab researchers have expedited accelerator mass spectrometer sample preparation and analysis time from days to minutes and moved a complex scientific process requiring accelerator physicists into routine laboratory usage.

    Ken Turteltaub, the leader of the Lab’s Biosciences and Biotechnology Division, sees the bio AMS advances as allowing researchers to undertake quantitative assessments of complex biological pathways.

    “We are hopeful that we’ll be able to quantify the individual steps in a metabolic pathway and be able to measure indicators of disease processes and factors important to why people differ in responses to therapeutics, to diet and other factors,” Turteltaub said.

    Graham Bench, the director of the Lab’s Center for Accelerator Mass Spectrometry, anticipates the upgrades will enable Lab researchers “to produce high-density data sets and tackle novel biomedical problems that in the past couldn’t be addressed.”

    Ted Ognibene, a chemist who has worked on AMS for 15 years and who co-developed the technique that accommodates liquid samples, also envisions new scientific work coming forth.

    two
    Ted Ognibene (left), a chemist who co-developed the technique that accommodates liquid samples for accelerator mass spectrometry, peers with biomedical scientist Mike Malfatti at the new biological AMS instrument that has been installed in the Laboratory’s biomedical building. Photo by George Kitrinos

    “We previously had the capability to detect metabolites, but now with the ability to see our results almost immediately for a fraction of the cost, it’s going to enable a lot more fundamental and new science to be done,” Ognibene said.

    Biological AMS is a technique in which carbon-14 is used as a tag to study with extreme precision and sensitivity complex biological processes, such as cancer, molecular damage, drug and toxin behavior, nutrition and other areas.

    Among the biomedical studies that will be funded through the five-year, $7.8 million National Institutes of Health grant for biological AMS work is one to try to develop a test to predict how people will respond to chemotherapeutic drugs.

    Another research project seeks to create an assay that is so sensitive that it can detect one cancer cell among one million healthy cells. If this work is successful, it could be possible to evaluate the metastasis potential of different primary human cancer cells.

    Lab biomedical scientist Mike Malfatti and two researchers - Paul Henderson, an associate professor, and Chong-Xian Pan, a medical oncologist — from the University of California, Davis Comprehensive Cancer Center, are using the AMS in a human trial with 50 patients to see how cancer patients respond or don’t respond to the chemotherapeutic drug carboplatin. This drug kills cancer cells by binding to DNA, and is toxic to rapidly dividing cells.

    The three researchers have the patients take a microdose of carboplatin — about 1/100th of a therapeutic dose — that has no toxicity or therapeutic value to evaluate how effectively the drug will bind to a person’s DNA during full dose treatment.

    Within a few days of patients receiving the microdose, the degree of drug binding is checked by blood sample, in which the DNA is isolated from white blood cells, or by tumor biopsy, in which the DNA is isolated from the tumor cells.

    The carboplatin dose is prepared with a carbon-14 tag. The DNA sample is analyzed using AMS and the instrument quantifies the carbon-14 level, with a high level of carbon-14 indicating a high level of drug binding to the DNA.

    “A high degree of binding indicates that you have a high probability of a favorable response to the drug,” Malfatti said. “Conversely, a low degree of binding means it is likely the person’s body won’t respond to the treatment.

    “If we can identify which people will respond to which chemotherapeutic drug, we can tailor the treatment to the individual.

    “There are many negative side effects associated with chemotherapy, such as nausea, loss of appetite, loss of hair and even death. We don’t want someone to receive chemotherapy that’s not going to help them, yet leave them with these negative side effects,” he added.

    Malfatti, Henderson and Pan also are using the AMS in pre-clinical studies to investigate the resistance or receptivity of other commonly used chemotherapeutic agents such as cisplatin, oxaliplatin and gemcitabine.

    Another team of researchers, led by Gaby Loots, a Lab biomedical scientist and an associate professor at the University of California, Merced, wants to use AMS to measure cancer cells labeled with carbon-14 to study the cancer cells’ migration to healthy tissues to determine how likely they are to form metastatic tumors.

    While today’s standard methods can detect tumors that are comprised of thousands of cells, the team would like to develop an assay with a thousand-fold better resolution – to detect one cancer cell among one million healthy ones.

    “The sensitivity of AMS allows us to develop more accurate, quantitative assays with single-cell resolution. Is the cancer completely gone, or do we see one cell worth of cancer DNA?” Loots noted.

    Some of the questions the team would like to answer are: 1) why certain cells metastasize? 2) how do cells metastasize? 3) what new methods can be developed to prevent metastasis?

    “Tumors shed cells all the time that enter our circulation. We would like to find ways to prevent the circulating tumor cells from forming metastatic tumors,” Loots continued.

    As a part of their research, the team members hope to determine whether cancer cells with stem-cell-like properties form more aggressive tumors.

    “We’re going to separate the cancer cells into stem-cell-like and non-stem-cell-like populations and seek to determine if they behave differently,” said Loots, who is working with fellow Lab biomedical scientists Nick Hum and Nicole Collette.

    See the full article here.

    LLNL Campus

    Operated by Lawrence Livermore National Security, LLC, for the Department of Energy’s National Nuclear Security
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  • richardmitnick 5:55 pm on October 16, 2014 Permalink | Reply
    Tags: , , , Cancer,   

    From BNL: “Scientists Map Key Moment in Assembly of DNA-Splitting Molecular Machine” 

    Brookhaven Lab

    October 15, 2014
    Justin Eure, (631) 344-2347 or Peter Genzer, (631) 344-3174

    The proteins that drive DNA replication—the force behind cellular growth and reproduction—are some of the most complex machines on Earth. The multistep replication process involves hundreds of atomic-scale moving parts that rapidly interact and transform. Mapping that dense molecular machinery is one of the most promising and challenging frontiers in medicine and biology.

    Now, scientists have pinpointed crucial steps in the beginning of the replication process, including surprising structural details about the enzyme that “unzips” and splits the DNA double helix so the two halves can serve as templates for DNA duplication.

    The research combined electron microscopy, perfectly distilled proteins, and a method of chemical freezing to isolate specific moments at the start of replication. The study—authored by scientists from the U.S. Department of Energy’s Brookhaven National Laboratory, Stony Brook University, Cold Spring Harbor Laboratory, and Imperial College, London—published on Oct. 15, 2014, in the journal Genes and Development.

    “The genesis of the DNA-unwinding machinery is wonderfully complex and surprising,” said study coauthor Huilin Li, a biologist at Brookhaven Lab and Stony Brook University. “Seeing this helicase enzyme prepare to surround and unwind the DNA at the molecular level helps us understand the most fundamental process of life and how that process might go wrong. Errors in copying DNA are found in certain cancers, and this work could one day help develop new treatment methods that stall or break dangerous runaway machinery.”

    The research picks up where two previous studies by Li and colleagues left off. They first determined the structure of the “Origin Recognition Complex” (ORC), a protein that identifies and attaches to specific DNA sites to initiate the entire replication process. The second study revealed how the ORC recruits, cracks open, and installs a crucial ring-shaped protein structure (Mcm2-7) that lies at the core of the helicase enzyme.

    But DNA replication is a bi-directional process with two helicases moving in opposite directions. The key question, then, was how does a second helicase core get recruited and loaded onto the DNA in the opposite orientation of the first?

    dr
    Three-dimensional model (based on electron microscopy data) of the double-ring structure loaded onto a DNA helix.

    “To our surprise, we found an intermediate structure with one ORC binding two rings,” said Brookhaven Lab biologist and lead author Jingchuan Sun. “This discovery suggests that a single ORC, rather than the commonly believed two-ORC system, loads both helicase rings.”

    One step further along, the researchers also determined the molecular architecture of the final double-ring structure left behind after the ORC leaves the system, offering a number of key biological insights.

    “We now have clues to how that double-ring structure stably lingers until the cell enters the DNA-synthesis phase much later on in replication,” said study coauthor Christian Speck of Imperial College, London. “This study revealed key regulatory principles that explain how the helicase activity is initially suppressed and then becomes reactivated to begin its work splitting the DNA.”

    three
    Precision methods, close collaboration
    Collaborating scientists and study coauthors Zuanning Yuan of Stony Brook University (standing), Huilin Li of Stony Brook and Brookhaven Lab (seated, back), and Jingchuan Sun of Brookhaven Lab (seated, front) examining protein structures.

    Examining these fleeting molecular structures required mastery of biology, chemistry, and electron microscopy techniques.

    “This three-way collaboration took advantage of each lab’s long standing collaboration and expertise,” said study coauthor Bruce Stillman of Cold Spring Harbor. “Imperial College and Cold Spring Harbor handled the challenging material preparation and functional characterization, while Brookhaven and Stony Brook led the sophisticated molecular imaging and three-dimensional image reconstruction.”

    The researchers used proteins from baker’s yeast—a model organism for the more complex systems found in animals. The scientists isolated the protein mechanisms involved in replication and removed structures that might otherwise complicate the images.

    Once the isolated proteins were mixed with DNA, the scientists injected chemicals to “freeze” the binding and recruitment process at intervals of 2, 7, and 30 minutes.

    They then used an electron microscope at Brookhaven to pin down the exact structures at each targeted moment in a kind of molecular time-lapse. Rather than the light used in a traditional microscope, this technique uses focused beams of electrons to illuminate a sample and form images with atomic resolution. The instrument produces a large number of two-dimensional electron beam images, which a computer then reconstructs into three-dimensional structure.

    “This technique is ideal because we’re imaging relatively massive proteins here,” Li said. “A typical protein contains three hundred amino acids, but these DNA replication mechanisms consist of tens of thousands of amino acids. The entire structure is about 20-nanometers across, compared to 4 nanometers for an average protein.”

    Unraveling the DNA processes at the most fundamental level, the focus of this team’s work, could have far-reaching implications.

    “The structural knowledge may help others engineer small molecules that inhibit DNA replication at specific moments, leading to new disease prevention or treatment techniques,” Li said.

    Additional collaborators on this research include Alejandra Fernandez, Alberto Riera, and Silvia Tognetti of the MRC Clinical Science Centre of Imperial College, London; and Zuanning Yuan of Stony Brook University.

    The research was funded by the National Institutes of Health (GM45436, GM74985) and the United Kingdom Medical Research Council.

    See the full article here.

    BNL Campus

    One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. The Laboratory’s almost 3,000 scientists, engineers, and support staff are joined each year by more than 5,000 visiting researchers from around the world.Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
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  • richardmitnick 3:30 pm on September 30, 2014 Permalink | Reply
    Tags: , , Cancer,   

    From Symmetry: “Accelerating the fight against cancer” 

    Symmetry

    September 30, 2014
    Glennda Chui

    As charged-particle therapies grow in popularity, physicists are working with other experts to make them smaller, cheaper and more effective—and more available to cancer patients in the United States.

    Once physicists started accelerating particles to high energies in the 1930s, it didn’t take them long to think of a killer app for this new technology: zapping tumors.

    Standard radiation treatments, which had already been around for decades, send X-rays straight through the tumor and out the other side of the body, damaging healthy tissue both coming and going. But protons and ions—atoms stripped of electrons—slow when they hit the body and come to a stop, depositing most of their destructive energy at their stopping point. If you tune a beam of protons or ions so they stop inside a tumor, you can deliver the maximum dose of radiation while sparing healthy tissue and minimizing side effects. This makes it ideal for treating children, whose developing bodies are particularly sensitive to radiation damage, and for cancers very close to vital tissues such as the optic nerves or spinal cord.

    proton
    Protons and electrons in an atom

    Today, nearly 70 years after American particle physicist Robert Wilson came up with the idea, proton therapy has been gaining traction worldwide and in the United States, where 14 centers are treating patients and nine more are under construction. Ions such as carbon, helium and oxygen are being used to treat patients in Germany, Italy, China and Japan. More than 120,000 patients had been treated with various forms of charged-particle therapy by the end of 2013, according to the Particle Therapy Co-Operative Group.

    New initiatives from CERN research center in Europe and the Department of Energy and National Cancer Institute in the United States are aimed at moving the technology along, assessing its strengths and limitations and making it more affordable.

    And physicists are still deeply involved. No one knows more about building and operating particle accelerators and detectors. But there’s a lot more to know. So they’ve been joining forces with physicians, engineers, biologists, computer scientists and other experts to make the equipment smaller, lighter, cheaper and more efficient and to improve the way treatments are done.

    pa
    particle Accelerator

    “As you get closer to the patient, you leave the world accelerator physicists live in and get closer to the land of people who have PhDs in medical physics,” says Stephen Peggs, an accelerator physicist at Brookhaven National Laboratory.

    “It’s alignment, robots and patient ergonomics, which require just the right skill sets, which is why it’s fun, of course, and one reason why it’s interesting—designing with patients in mind.”

    Knowing where to stop

    The collaborations that make charged-particle therapy work go back a long way. The first experimental treatments took place in 1954 at what is now Lawrence Berkeley National Laboratory. Later scientists at Fermi National Accelerator Laboratory designed and built the circular accelerator at the heart of the first hospital-based proton therapy center in the United States, opened in 1990 at California’s Loma Linda University Medical Center.

    A number of private companies have jumped into the field, opening treatment centers, selling equipment and developing more compact and efficient treatment systems that are designed to cut costs. ProTom International, for instance, recently received US Food and Drug Administration approval for a system that’s small enough and light enough to ship on a plane and move in through a door, so it will no longer be necessary to build the treatment center around it. Other players include ProCure, Mevion, IBA, Varian Medical Systems, ProNova, Hitachi, Sumitomo and Mitsubishi.

    The goal of any treatment scheme is to get the beam to stop in exactly the right spot; the most advanced systems scan a beam back and forth to “paint” the 3-D volume of the tumor with great precision. Aiming it is not easy, though. Not only is every patient’s body different—a unique conglomeration of organs and tissues of varying densities—but every patient breathes, so the target is in constant motion.

    Doctors use X-ray CT scans—the CT stands for “computed tomography”—to make a 3-D image of the tumor and its surroundings so they can calculate the ideal stopping point for the proton beam. But since protons don’t travel through the body exactly the same way X-rays do—their paths are shifted by tiny, rapid changes in the tissues they encounter along the way—their end points can differ slightly from the predicted ones.

    Physicists are trying to reduce that margin of error with a technology called proton CT.

    centers
    There are 49 charged-particle treatment centers operating worldwide, including 14 in the United States, and 27 more under construction. This map shows the number of patients treated through the end of 2013 in centers that are now in operation. Source: Particle Therapy Co-Operative Group.
    Artwork by: Sandbox Studio, Chicago with Shawna X.

    Reconnoitering with proton CT

    The idea is simple: Use protons rather than X-rays to make the images. The protons are tuned to high enough energies that they go through the body without stopping, depositing about one-tenth as much radiation along their path as X-rays do.

    Detectors in front of and behind the body pinpoint where each proton beam enters and leaves, and a separate detector measures how much energy the protons lose as they pass through tissues. By directing proton beams through the patient from different angles, doctors can create a 3-D image that tells them, much more accurately than X-rays, how to tune the proton beam so it stops inside the tumor.

    Two teams are now in friendly competition, testing rival ways to perform proton CT on “phantom” human heads made of plastic. Both approaches are based on detectors that are staples in particle physics.

    One team is made up of researchers from Northern Illinois University, Fermilab, Argonne National Laboratory and the University of Delhi in India and funded by the US Army Medical Research Acquisition Center in Maryland. They use a pair of fiber trackers on each side of the phantom head to pinpoint where the proton beams enter and exit. Each tracker contains thousands of thin plastic fibers. When a proton hits a fiber, it gives off a flash of light that is picked up by another physics standby—a silicon photomultiplier—and conveyed to a detector.

    The team is testing this system, which includes computers and software for turning the data into images, at the CDH Proton Center in Warrenville, Illinois.

    “The point is to demonstrate you can get the image quality you need to target the treatment more accurately with a lower radiation dose level than with X-ray CT,” says Peter Wilson, principal investigator for the Fermilab part of the project.

    The second project, a collaboration between researchers at Loma Linda, University of California, Santa Cruz, and Baylor University, is fi-nanced by a $2 million grant from the National Institutes of Health. Their proton CT system is based on silicon strip detectors the Santa Cruz group developed for the Fermi Gamma-ray Space Telescope and the ATLAS experiment at CERN, among others. It’s being tested at Loma Linda.

    NASA Fermi Telescope
    NASA/Fermi

    CERN ATLAS New
    CERN/ATLAS

    “We know how to detect charged particles with silicon detectors. Charged particles for us are duck soup,” says UCSC particle physicist Hartmut Sadrozinski, who has been working with these detectors for more than 30 years. Since a single scan requires tracking about a billion protons, the researchers also introduced software packages developed for high-energy physics to analyze the high volume of data coming into the detector.

    Proton CT will have to get a lot faster before it’s ready for the treatment room. In experiments with the phantom head, the system can detect a million protons per second, completing a scan in about 10 minutes, Sadrozinski says; the goal is to bring that down to 2 to 3 minutes, reducing the time the patient has to hold still and ensuring accurate images and dose delivery.
    Trimming the size and cost of ion therapy

    The first ion therapy center opened in Japan in 1994; by the end of 2013 centers in Japan, China, Germany and Italy had treated nearly 13,000 patients.

    There’s reason to think ions could be more effective than protons or X-rays for treating certain types of cancer, according to a recent review of the field published in Radiation Oncology by researchers from the National Cancer Institute and Walter Reed National Military Medical Center. Ions deliver a more powerful punch than protons, causing more damage to a tumor’s DNA, and patient treatments have shown promise.

    But the high cost of building and operating treatment centers has held the technology back, the researchers wrote; and long-term research on possible side effects, including the possibility of triggering secondary cancers, is lacking.

    The cost of building ion treatment centers is higher in part because the ions are so much heavier than protons. You need bigger magnets to steer them around an accelerator, and heavier equipment to deliver them to the patient.

    Two projects at Brookhaven National Laboratory aim to bring the size and cost of the equipment down.

    One team, led by accelerator physicist Dejan Trbojevic, has developed and patented a simpler, less expensive gantry that rotates around a stationary patient to aim an ion beam at a tumor from various angles. Gantries for ion therapy can be huge—the one in use at the Heidelberg Ion-Beam Therapy Center in Germany weighs 670 tons and is tall as a jetliner. The new design shrinks the size of the gantry by making a single set of simpler, smaller magnets do double duty, both bending and focusing the particle beam.

    In the second project, Brookhaven scientists are working with a Virginia company, Best Medical International, to design a system for treating patients with protons, carbon ions and other ion beams. Called the ion Rapidly Cycling Medical Synchrotron (iRCMS), it is designed to deliver ions to patients in smaller, more rapid pulses. With smaller pulses, the diameter of the beam also shrinks, along with the size of the magnets used to steer it. Brookhaven is building one of the system’s three magnet girders, radio-frequency acceleration cavities and a power supply for a prototype system. The end product must be simple and reliable enough for trained hospital technicians to operate for years.

    “A particle accelerator for cancer treatment has to be industrial, robust—not the high-tech, high-performance, typical machine we’re used to,” says Brookhaven’s Peggs, one of the lead scientists on the project. “It’s more like a Nissan than a Ferrari.”

    image
    Artwork by: Sandbox Studio, Chicago with Shawna X.

    Launching a CERN initiative for cancer treatment

    CERN, the international particle physics center in Geneva, is best known to many as the place where the Higgs boson was discovered in 2012. In 1996 it began collaborating on a study called PIMMS that designed a system for delivering both proton and ion treatments. That system evolved into the equipment at the heart of two ion therapy centers: CNAO, the National Center for Oncological Treatment in Pavia, Italy, which treated its first patient in 2011, and MedAustron, scheduled to open in Austria in 2015.

    Now scientists at CERN want to spearhead an international collaboration to design a new, more compact treatment system that will incorporate the latest particle physics technologies. It’s part of a larger CERN initiative launched late last year with a goal of contributing to a global system for treating cancer with charged-particle beams.

    Part of an existing CERN accelerator, the Low Energy Ion Ring, will be converted into a facility to provide various types of charged-particle beams for research into how they affect healthy and cancerous tissue. The lab will also consider developing detectors for making medical images and controlling the treatment beam, investigating ways to control the dose the patient receives and adapting large-scale computing for medical applications.

    CERN Low Energy Ion Ring
    CERN Low Energy Ion Ring

    CERN will provide seed funding and seek out other funding from foundations, philanthropists and other sources, such as the European Union.

    “Part of CERN’s mission is knowledge transfer,” says Steve Myers, director of the medical initiative, who spent the past five years running the Large Hadron Collider as director of accelerators and technology for CERN.

    CERN LHC Map
    CERN LHC Grand Tunnel
    CERN LHC particles
    CERN/LHC

    “We would like to make the technologies we have developed for particle physics available to other fields of research simply because we think it’s a nice thing to do,” he says. “All the things we do are related to the same goal, which is treating cancer tumors in the most effective and efficient way possible.”

    Expanding the options in the US

    In the US, the biggest barrier to setting up ion treatment centers is financial: Treatment centers cost hundreds of millions of dollars. Unlike in Europe and Asia, no government funding is available, so these projects have to attract private investors. But without rigorous studies showing that ion therapy is worth the added cost in terms of eradicating cancer, slowing its spread or improving patients’ lives, investors are reluctant to pony up money and insurance companies are reluctant to pay for treatments.

    Studies that rigorously compare the results of proton or ion treatment with standard radiation therapy are just starting, says James Deye, program director for medical physics at the National Cancer Institute’s radiation research program.

    The need for more research on ion therapy has caught the attention of the Department of Energy, whose Office of High Energy Physics oversees fundamental, long-term accelerator research in the US. A 2010 report, “Accelerators for America’s Future,” identified ion therapy as one of a number of areas where accelerator research and development could make important contributions to society.

    In January 2013, more than 60 experts from the US, Japan and Europe met at a workshop sponsored by the DOE and NCI to identify areas where more research is needed on both the hardware and medical sides to develop the ion therapy systems of the future. Ideally, the participants concluded, future facilities should offer treatment with multiple types of charged particles—from protons to lithium, helium, boron and carbon ions—to allow researchers to compare their effectiveness and individual patients to get more than one type of treatment.

    In June, the DOE’s Accelerator Stewardship program asked researchers to submit proposals for seed funding to improve accelerator and beam delivery systems for ion therapy.

    “If there are accelerator technologies that can better enable this type of treatment, our job is to apply our R&D and technical skills to try to improve their ability to do so,” says Michael Zisman, an accelerator physicist from Lawrence Berkeley National Laboratory who is temporarily detailed to the DOE Office of High Energy Physics.

    “Ideally we hope there will be partnerships between labs, industry, universities and medical facilities,” he says. “We don’t want good technology ideas in search of a problem. We rather want to make sure our customers are identifying real problems that we believe the application of improved accelerator technology can actually solve.”

    See the full article here.

    Symmetry is a joint Fermilab/SLAC publication.


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  • richardmitnick 8:54 pm on September 28, 2014 Permalink | Reply
    Tags: , , Cancer, ,   

    From MIT: “Biologists find an early sign of cancer” 


    MIT News

    September 28, 2014
    Anne Trafton | MIT News Office

    Patients show boost in certain amino acids years before diagnosis of pancreatic cancer.

    Years before they show any other signs of disease, pancreatic cancer patients have very high levels of certain amino acids in their bloodstream, according to a new study from MIT, Dana-Farber Cancer Institute, and the Broad Institute.

    cancer
    Christine Daniloff/MIT

    This finding, which suggests that muscle tissue is broken down in the disease’s earliest stages, could offer new insights into developing early diagnostics for pancreatic cancer, which kills about 40,000 Americans every year and is usually not caught until it is too late to treat.

    The study, which appears today in the journal Nature Medicine, is based on an analysis of blood samples from 1,500 people participating in long-term health studies. The researchers compared samples from people who were eventually diagnosed with pancreatic cancer and samples from those who were not. The findings were dramatic: People with a surge in amino acids known as branched chain amino acids were far more likely to be diagnosed with pancreatic cancer within one to 10 years.

    “Pancreatic cancer, even at its very earliest stages, causes breakdown of body protein and deregulated metabolism. What that means for the tumor, and what that means for the health of the patient — those are long-term questions still to be answered,” says Matthew Vander Heiden, an associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the paper’s senior authors.

    The paper’s other senior author is Brian Wolpin, an assistant professor of medical oncology at Dana-Farber. Wolpin, a clinical epidemiologist, assembled the patient sample from several large public-health studies. All patients had their blood drawn when they began participating in the studies and subsequently filled out annual health questionnaires.

    Working with researchers at the Broad Institute, the team analyzed blood samples for more than 100 different metabolites — molecules, such as proteins and sugars, produced as the byproducts of metabolic processes.

    “What we found was that this really interesting signature fell out as predicting pancreatic cancer diagnosis, which was elevation in these three branched chain amino acids: leucine, isoleucine, and valine,” Vander Heiden says. These are among the 20 amino acids — the building blocks for proteins — normally found in the human body.

    Some of the patients in the study were diagnosed with pancreatic cancer just one year after their blood samples were taken, while others were diagnosed two, five, or even 10 years later.

    “We found that higher levels of branched chain amino acids were present in people who went on to develop pancreatic cancer compared to those who did not develop the disease,” Wolpin says. “These findings led us to hypothesize that the increase in branched chain amino acids is due to the presence of an early pancreatic tumor.”

    Early protein breakdown

    Vander Heiden’s lab tested this hypothesis by studying mice that are genetically programmed to develop pancreatic cancer. “Using those mouse models, we found that we could perfectly recapitulate these exact metabolic changes during the earliest stages of cancer,” Vander Heiden says. “What happens is, as people or mice develop pancreatic cancer, at the very earliest stages, it causes the body to enter this altered metabolic state where it starts breaking down protein in distant tissues.”

    “This is a finding of fundamental importance in the biology of pancreatic cancer,” says David Tuveson, a professor at the Cancer Center at Cold Spring Harbor Laboratory who was not involved in the work. “It really opens a window of possibility for labs to try to determine the mechanism of this metabolic breakdown.”

    The researchers are now investigating why this protein breakdown, which has not been seen in other types of cancer, occurs in the early stages of pancreatic cancer. They suspect that pancreatic tumors may be trying to feed their own appetite for amino acids that they need to build cancerous cells. The researchers are also exploring possible links between this early protein breakdown and the wasting disease known as cachexia, which often occurs in the late stages of pancreatic cancer.

    Also to be answered is the question of whether this signature could be used for early detection. The findings need to be validated with more data, and it may be difficult to develop a reliable diagnostic based on this signature alone, Vander Heiden says. However, he believes that studying this metabolic dysfunction further may reveal additional markers, such as misregulated hormones, that could be combined to generate a more accurate test.

    The findings may also allow scientists to pursue new treatments that would work by targeting tumor metabolism and cutting off a tumor’s nutrient supply, Vander Heiden says.

    MIT’s contribution to this research was funded by the Lustgarten Foundation, the National Institutes of Health, the Burroughs Wellcome Fund, and the Damon Runyon Cancer Research Foundation.

    See the full article here.

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  • richardmitnick 7:07 am on September 23, 2014 Permalink | Reply
    Tags: , Cancer,   

    From Cornell: “Gene linked to development of skin cancer in mice” 

    Cornell Bloc

    Cornell University

    Sept. 22, 2014
    Merry R. Buckley

    New research on an enzyme linked to cancer development shows that 37 percent of mice that produce excessive quantities of the enzyme developed skin tumors within four to 12 months of birth, and many of these growths progressed to highly invasive squamous cell carcinoma, a common form of skin cancer.

    This finding, published online Sept. 11 in the journal Cancer Research, provides the first genetic link between the activity of the enzyme, called PAD2, and cancer progression, and provides important supporting evidence for further studies aimed at using PAD2 inhibitors to block carcinoma progression in humans.

    Lead author Scott Coonrod, the Judy Wilpon Associate Professor of Cancer Biology at the Baker Institute for Animal Health in Cornell’s College of Veterinary Medicine, has studied links between PAD2 and other PAD (peptidylarginine deiminase) enzymes and cancer for some time. Those prior studies suggested that PAD2 plays an important role in regulating genes during cancer progression; however, a direct link between PADs and tumor progression had not yet been proven. Other work from the lab suggested that PAD2 is found at high concentrations in several tumor types, but it was not known whether these elevated levels of the enzyme were causing cancer or merely a consequence of tumor progression.

    two
    Ph.D. student and study co-author Sachi Horibata and Scott Coonrod, associate professor at the Baker Institute for Animal Health, work on research that linked an enzyme to cancer development.

    To directly test for links between PAD2 and cancer, the researchers engineered mice to overexpress PAD2 and then looked to see whether these mice developed cancer.

    Coonrod thinks that the reason PAD2 overproduction in the skin may cause cancer is likely due to its ability to promote inflammation.

    “Inflammation has long been known to play an important role in the development of many types of cancer,” he says. “Recent studies provide strong evidence that inflammation represents one of the 10 hallmarks of cancer.“It’s becoming clear that the activity of PAD enzymes seems to be low in most normal tissues, but becomes elevated in a whole range of inflammatory diseases – like rheumatoid arthritis, colitis and lupus. PAD activity is very high in the affected tissues and seems to be driving a lot of the inflammatory conditions that cause these diseases.”

    To test whether PAD2 might be promoting inflammation, Coonrod and his colleagues looked for classical markers of inflammation in the growths and found that a number of these markers were significantly elevated in the mouse tumors. To further test their hypothesis, they overexpressed PAD2 in human cell lines to better understand how the enzyme might behave in human tissue. They found that, similar to the mouse studies, PAD2 overproduction made these human cells more invasive and also enhanced inflammatory marker expression.

    Together, these studies suggest that increased PAD activity in human skin, and potentially other tissues, promotes an inflammatory environment that is favorable for cancer development, says Coonrod. His longtime collaborator, Paul Thompson at the University of Massachusetts Memorial Medical Center, has developed a range of new PAD inhibitors, and the team is now testing whether these compounds might suppress carcinoma progression in mouse models of both skin and mammary glands.

    Two of Coonrod’s co-authors on the paper, PAD2 Overexpression in Transgenic Mice Promotes Spontaneous Skin Neoplasia, are postdoctoral associate John McElwee, Ph.D. ’13, and graduate student Sunish Mohanan, DVM, who carried out some of the research for their thesis projects in Coonrod’s lab.

    See the full article here.

    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

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  • richardmitnick 6:44 pm on September 22, 2014 Permalink | Reply
    Tags: , , Cancer, ,   

    From Stanford: “Stanford researchers create ‘evolved’ protein that may stop cancer from spreading” 

    Stanford University Name
    Stanford University

    September 21, 2014
    Tom Abate

    Experimental therapy stopped the metastasis of breast and ovarian cancers in lab mice, pointing toward a safe and effective alternative to chemotherapy.

    A team of Stanford researchers has developed a protein therapy that disrupts the process that causes cancer cells to break away from original tumor sites, travel through the bloodstream and start aggressive new growths elsewhere in the body.

    This process, known as metastasis, can cause cancer to spread with deadly effect.

    “The majority of patients who succumb to cancer fall prey to metastatic forms of the disease,” said Jennifer Cochran, an associate professor of bioengineering who describes a new therapeutic approach in Nature Chemical Biology.

    Today doctors try to slow or stop metastasis with chemotherapy, but these treatments are unfortunately not very effective and have severe side effects.

    The Stanford team seeks to stop metastasis, without side effects, by preventing two proteins – Axl and Gas6 – from interacting to initiate the spread of cancer.

    Axl proteins stand like bristles on the surface of cancer cells, poised to receive biochemical signals from Gas6 proteins.

    When two Gas6 proteins link with two Axls, the signals that are generated enable cancer cells to leave the original tumor site, migrate to other parts of the body and form new cancer nodules.

    To stop this process Cochran used protein engineering to create a harmless version of Axl that acts like a decoy. This decoy Axl latches on to Gas6 proteins in the bloodstream and prevents them from linking with and activating the Axls present on cancer cells.

    In collaboration with Professor Amato Giaccia, co-director of the Radiation Biology Program in the Stanford Cancer Center, the researchers gave intravenous treatments of this bioengineered decoy protein to mice with aggressive breast and ovarian cancers.

    two
    Jennifer Cochran and Amato Giaccia are members of a team of researchers who have developed an experimental therapy to treat metastatic cancer.

    Mice in the breast cancer treatment group had 78 percent fewer metastatic nodules than untreated mice. Mice with ovarian cancer had a 90 percent reduction in metastatic nodules when treated with the engineered decoy protein.

    “This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” Giaccia said. “It could open up a new approach to cancer treatment.”

    Giaccia and Cochran are scientific advisors to Ruga Corp., a biotech startup in Palo Alto that has licensed this technology from Stanford. Further preclinical and animal tests must be done before determining whether this therapy is safe and effective in humans.

    Greg Lemke, of the Molecular Neurobiology Laboratory at the Salk Institute, called this “a prime example of what bioengineering can do” to open up new therapeutic approaches to treat metastatic cancer.

    “One of the remarkable things about this work is the binding affinity of the decoy protein,” said Lemke, a noted authority on Axl and Gas6 who was not part of the Stanford experiments.

    “The decoy attaches to Gas6 up to a hundredfold more effectively than the natural Axl,” Lemke said. “It really sops up Gas6 and takes it out of action.”
    Directed evolution

    The Stanford approach is grounded on the fact that all biological processes are driven by the interaction of proteins, the molecules that fit together in lock-and-key fashion to perform all the tasks required for living things to function.

    In nature proteins evolve over millions of years. But bioengineers have developed ways to accelerate the process of improving these tiny parts using technology called directed evolution. This particular application was the subject of the doctoral thesis of Mihalis Kariolis, a bioengineering graduate student in Cochran’s lab.

    Using genetic manipulation, the Stanford team created millions of slightly different DNA sequences. Each DNA sequence coded for a different variant of Axl.

    The researchers then used high-throughput screening to evaluate over 10 million Axl variants. Their goal was to find the variant that bound most tightly to Gas6.

    Kariolis made other tweaks to enable the bioengineered decoy to remain in the bloodstream longer and also to tighten its grip on Gas6, rendering the decoy interaction virtually irreversible.

    Yu Rebecca Miao, a postdoctoral scholar in Giaccia’s lab, designed the testing in animals and worked with Kariolis to administer the decoy Axl to the lab mice. They also did comparison tests to show that sopping up Gas6 resulted in far fewer secondary cancer nodules.

    Irimpan Mathews, a protein crystallography expert at SLAC National Accelerator Laboratory, joined the research effort to help the team better understand the binding mechanism between the Axl decoy and Gas6.

    Protein crystallography captures the interaction of two proteins in a solid form, allowing researchers to take X-ray-like images of how the atoms in each protein bind together. These images showed molecular changes that allowed the bioengineered Axl decoy to bind Gas6 far more tightly than the natural Axl protein.
    Next steps

    Years of work lie ahead to determine whether this protein therapy can be approved to treat cancer in humans. Bioprocess engineers must first scale up production of the Axl decoy to generate pure material for clinical tests. Clinical researchers must then perform additional animal tests in order to win approval for and to conduct human trials. These are expensive and time-consuming steps.

    But these early, hopeful results suggest that the Stanford approach could become a nontoxic way to fight metastatic cancer.

    Glenn Dranoff, a professor of medicine at Harvard Medical School and a leading researcher at the Dana-Farber Cancer Institute, reviewed an advance copy of the Stanford paper but was otherwise unconnected with the research. “It is a beautiful piece of biochemistry and has some nuances that make it particularly exciting,” Dranoff said, noting that tumors often have more than one way to ensure their survival and propagation.

    Axl has two protein cousins, Mer and Tyro3, that can also promote metastasis. Mer and Tyro3 are also activated by Gas6.

    “So one therapeutic decoy might potentially affect all three related proteins that are critical in cancer development and progression,” Dranoff said.

    Erinn Rankin, a postdoctoral fellow in the Giaccia lab, carried out proof of principle experiments that paved the way for this study.

    Other co-authors on the Nature Chemical Biology paper include Douglas Jones, a former doctoral student, and Shiven Kapur, a postdoctoral scholar, both of Cochran’s lab, who contributed to the protein engineering and structural characterization, respectively.

    Cochran said Stanford’s support for interdisciplinary research made this work possible.

    Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health) provided seed funds that allowed Cochran and Mathews to collaborate on protein structural studies.

    The Stanford Wallace H. Coulter Translational Research Grant Program, which supports collaborations between engineers and medical researchers, supported the efforts of Cochran and Giaccia to apply cutting-edge bioengineering techniques to this critical medical need.

    See the full article here.

    Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

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  • richardmitnick 10:10 am on September 14, 2014 Permalink | Reply
    Tags: , , Cancer, , New Technology,   

    From Rutgers- “Novel Local Morphologic Scale: Applications in Disease Diagnosis and Prognosis” 

    Rutgers University
    Rutgers University

    Rutgers Technology

    Invention Summary

    Timely and accurate diagnosis of disease pathologies is critical to providing effective treatment to patients. Rutgers scientists have developed a novel local morphologic scale (LMS) to rapidly and automatically select, quantify and classify tissue/specimen topologies using parallelized computations. This unique tool has the ability to define features for every special image location and generate subsequent scene segmentation and classification for each location. Further this technology is free from shape constraints and generates output based on local structure attributes of complex histological images. This innovation has been successfully utilized in discriminating tumor versus stromal regions by classifying oncogenic tumor infiltrating lymphocytes (biomarker) in ovarian cancer tissue microarrays. Additionally, this technology has been applied across 3 other domains (prostate, breast) under two different stains illustrating its robustness to domain selection. This technology can be immensely useful to identify regions of interest, model heterogeneity of the underlying topology and generate digital signatures. It can also be used to train supervised classifiers to identify similar structural signatures in an image and therefore reduce or eliminate and observer variability.

    Market Application

    Disease Diagnosis, Digital Pathology, Histopathology, Computer Aided Diagnosis (CAD), Tissue Classification, Disease Monitoring and Prognosis, Lymphocyte Infiltration, Cancer.

    Advantages

    Signatures derived from cancerous versus non-cancerous tissues differ greatly. This tool can be highly instrumental in classifying cancerous versus non-cancerous tissue, can reliably and accurately account for cell shape and phenotypes, and provide accurate tissue classification, enabling pathologists to visually discern the two regions.

    Intellectual Property & Development Status
    Patent pending.

    Select Publication
    Janowczyk, A, Chandran S, Feldman MD, Madabhushi A. (2011). Local morphologic scale: Application to segmenting tumor infiltrating lymphocytes in ovarian cancer TMAs. SPIE http://lcib.rutgers.edu/publications/ Andrew/SPIE2011.pdf

    See the full articled here.

    Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

    Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.

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  • richardmitnick 1:46 pm on September 5, 2014 Permalink | Reply
    Tags: , Cancer, ,   

    From PBS NOVA: “New Drug Clears Cancer Cells Through Immune System Judo” 

    PBS NOVA

    NOVA

    Fri, 05 Sep 2014
    Tim De Chant

    For years, scientists have been probing various immune response proteins in the hopes of finding a new way to target and destroy cancer cells. Yesterday, two months ahead of schedule, the FDA approved a drug that does just that, targeting the protein “programmed cell death 1,” or PD-1. While not the first drug to use the immune system to fight cancer, it may be the most promising to date.

    Pembrolizumab is currently approved for advanced melanoma patients who have no other treatment options left. In clinical trials, tumors shrank in 24% of patients, and in one particular trial, 69% of patients were alive after one year of pembrolizumab treatment, a number that shocked the doctors in charge.

    melanoma
    Melanoma cell

    Pembrolizumab works by suppressing the expression of PD-1. In a healthy cell, PD-1 is active and present on the surface of a cell. But when a cell is nearing the end of it’s life, PD-1 expression tapers off. Immune cells recognize this signal and come in to clear away the dead or dying cell. Researchers have discovered that, in many tumors, PD-1 continues to be expressed. By preventing PD-1 from appearing on the surface of a cell, they predicted that cancer cells would be eliminated by the body’s own defenses.

    Doctors are hopeful that therapies which target PD-1 will give patients new options with fewer side effects than traditional chemotherapy. Andrew Pollack, reporting for the New York Times:

    “This is really opening up a whole new avenue of effective therapies previously not available,” said Dr. Louis M. Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington and a spokesman for the American Association for Cancer Research. “It allows us to see a time when we can treat many dreaded cancers without resorting to cytotoxic chemotherapy.”

    Pembrolizumab is being marketed as Keytruda by Merck, the drug’s developer. Priced at $12,500 per month or $150,000 per year, the drug is apparently more expensive than other cancer drugs. Pollack reports that some cancer doctors have expressed concern that the high price tag will be too dear for some patients.

    Pembrolizumab is an antibody that specifically targets PD-1, so side effects tend to be less severe than with more general chemotherapy. Patients still run the risk of a potentially harmful inflammatory response—a sign of a runaway immune system, though most tolerated the drug well.

    For now, pembrolizumab is limited to patients with advanced melanoma that doesn’t respond to other treatments, but Merck has seen promising results with lung and kidney cancers. Other pharmaceutical companies are racing to get their PD-1 drugs approved, too. As more drugs come on the market, and new ones are calibrated for different cancers, the next few years could be the beginning of a new era in clinical cancer treatments.

    See the full article here.

    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.

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  • richardmitnick 3:02 pm on August 16, 2014 Permalink | Reply
    Tags: , , , Cancer,   

    From Argonne Lab: “New nanotech invention improves effectiveness of the ‘penicillin of cancer'” 

    News from Argonne National Laboratory

    August 13, 2014
    Jared Sagoff

    Scientists at the U.S. Department of Energy’s Argonne National Laboratory have added a new weapon to oncologists’ arsenal of anti-cancer therapies.

    By combining magnetic nanoparticles with one of the most common and effective chemotherapy drugs, Argonne researchers have created a way to deliver anti-cancer drugs directly into the nucleus of cancer cells.

    nano
    “This new method gives a way of delivering the dose of therapeutic cargo much more directly, which will enable us to have the same overall effect with a lower total dose, reducing the unpleasant and dangerous side effects of chemotherapy,” said oncologist Ezra Cohen, an author of the study.

    Researchers at Argonne’s Center for Nanoscale Materials and oncologists at the University of Chicago created nano-sized bubbles, or “micelles,” that contained two ingredients at their centers: magnetic nanoparticles of iron oxide and cisplatin, a conventional chemotherapy drug also known as “the penicillin of cancer.”

    Cisplatin works by directly blocking DNA replication within the cancer cell. However, in order to work, the cisplatin has to make it from the bloodstream through the somewhat rigid barrier of the cell membrane.

    “When someone is given a dose of chemotherapy, typically much of the drug doesn’t actually make it into the cancer cells. In addition, some cancer patients are sensitive to this drug due to impaired kidney function,” said oncologist Ezra Cohen, an author of the study. “This new method gives a way of delivering the dose of therapeutic cargo much more directly, which will enable us to have the same overall effect with a lower total dose, reducing the unpleasant and dangerous side effects of chemotherapy.”

    “This technique could potentially allow us to increase the proportion of cisplatin in cancer cells by a hundredfold, making it that much more effective a chemotherapeutic agent,” he added.

    Like the membranes of cancer cells themselves, the micelles are made up of a polymer material whose outer surfaces are hydrophilic, which means they are attracted to water, while the inner parts are hydrophobic, repelling water. “In addition, the surface of micelles can be equipped with targeting molecules capable of recognizing malignancy,” said Argonne nanoscientist Elena Rozhkova, lead author of the study.

    Rozhkova and her colleagues still needed a way to get the cisplatin into the nucleus of the cancer cell after the micelle had attached to it. To do so, they also encapsulated iron oxide nanoparticles within the micelle along with the cisplatin. These nanoparticles served as tiny “heaters” that were turned on by an applied magnetic field, which caused the micelle container to collapse and release the cisplatin.

    This was not the first time scientists had used applied nanomagnetic heat sources as a way to attack cancer cells, but the more targeted approach of the micelles allowed the researchers to use a much lower amount of heat and much less magnetic material, thereby risking less damage to healthy cells.

    In order to see the action of the nanoparticles and cisplatin as the micelle collapsed, the researchers used the Hard X-Ray Nanoprobe at Argonne’s Advanced Photon Source. “Normally, it’s difficult to see how cisplatin is delivered into organelles like the nucleus, but with this technology we can see simultaneously how the drug delivery happens, how the nanoparticles interact with the cell’s membrane and the cell’s response,” said Argonne nanoscientist Volker Rose.

    The study, entitled Efficient cisplatin pro-drug delivery visualized with sub-100 nm resolution: interfacing engineered thermosensitive magnetomicelles with a living system, appeared online in the June 6 issue of Advanced Materials Interfaces.

    The materials characterization and synthesis work was performed at the Center for Nanoscale Materials and the Advanced Photon Source, both DOE Office of Science User Facilities. The medical aspects of the research, including animal studies, were supported by the University of Chicago.

    The Center for Nanoscale Materials at Argonne National Laboratory is one of the five DOE Nanoscale Science Research Centers (NSRCs), premier national user facilities for interdisciplinary research at the nanoscale, supported by the DOE Office of Science. Together the NSRCs comprise a suite of complementary facilities that provide researchers with state-of-the-art capabilities to fabricate, process, characterize and model nanoscale materials, and constitute the largest infrastructure investment of the National Nanotechnology Initiative. The NSRCs are located at DOE’s Argonne, Brookhaven, Lawrence Berkeley, Oak Ridge and Sandia and Los Alamos National Laboratories. For more information about the DOE NSRCs, please visit the Office of Science website.

    See the full article here.

    Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science. For more visit http://www.anl.gov.

    The Advanced Photon Source at Argonne National Laboratory is one of five national synchrotron radiation light sources supported by the U.S. Department of Energy’s Office of Science to carry out applied and basic research to understand, predict, and ultimately control matter and energy at the electronic, atomic, and molecular levels, provide the foundations for new energy technologies, and support DOE missions in energy, environment, and national security. To learn more about the Office of Science X-ray user facilities, visit http://science.energy.gov/user-facilities/basic-energy-sciences/.

    Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science

    Argonne Lab Campus

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