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  • richardmitnick 9:28 pm on November 26, 2015 Permalink | Reply
    Tags: , Cancer,   

    From TUM: “TUM sets the next milestone in biomedicine” 

    Techniche Universitat Munchen

    Techniche Universitat Munchen


    At TranslaTUM interdisciplinary teams of engineers, scientists and clinicians will work together to quickly “translate” research findings into practical applications, hence the name TranslaTUM. (Picture: doranth post architekten GmbH)

    Translational cancer research will be the focus of the new TranslaTUM central institute at the Technical University of Munich (TUM). The topping-out ceremony for the new research building (investment volume of approx. EUR 60 million) has just taken place. Biomedical research connects at all three TUM locations. Located on the clinic campus in Bogenhausen, TranslaTUM will provide interdisciplinary teams bringing together engineers, scientists and clinicians with the ideal environment to quickly “translate” research findings into practical applications (diagnostics, therapies), hence the name TranslaTUM. The Chair of Medical Sensor Technology, a position which is in the process of being filled, will also be based at the new central institute to ensure full integration into clinical practice.

    The German federal government is financing the new research center to the tune of EUR 24 million thanks to the approval of the expert committee of the German Council of Science and Humanities – which was impressed with the potential cross-regional reach of the TranslaTUM concept – and the excellent caliber of the scientists involved. The founding director of the new central institute is the renowned nuclear medicine scientist Prof. Markus Schwaiger.

    TranslaTUM is part of an overarching concept which the university is implementing step-by-step. Biomedical research activities are being expanded and interlinked across all three main TUM campuses. In addition to TranslaTUM, there is the Bavarian Nuclear Magnetic Resonance Center (Garching), the TUM Center for Functional Protein Assemblies (CPA) (Garching) and the Klaus Tschira Foundation’s Multiple Sclerosis Research Center (Munich). TUM’s MUNICH SCHOOL OF BIOENGINEERING is an integrative research center that provides a common teaching and research platform for all relevant medical engineering activities across different departments, including imaging technologies.

    See the full article here .

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    Techniche Universitat Munchin Campus

    Technische Universität München (TUM) is one of Europe’s top universities. It is committed to excellence in research and teaching, interdisciplinary education and the active promotion of promising young scientists. The university also forges strong links with companies and scientific institutions across the world. TUM was one of the first universities in Germany to be named a University of Excellence. Moreover, TUM regularly ranks among the best European universities in international rankings.

  • richardmitnick 4:23 pm on November 16, 2015 Permalink | Reply
    Tags: , Cancer, Help fight childhood cancer,   

    From HFCC at WCG: “New research phase will attack more types of childhood cancer” 

    New WCG Logo

    16 Nov 2015
    Dr. Akira Nakagawara, MD, PhD
    CEO of the Saga Medical Center KOSEIKAN and President Emeritus, Chiba Cancer Center

    Phase 2 of Help Fight Childhood Cancer will expand on the breakthrough discoveries from Phase 1. New collaborators, new disease targets and new therapy options will mean new hope for even more pediatric patients afflicted with cancer.


    Last year, our Help Fight Childhood Cancer (HFCC) team announced a breakthrough discovery with the potential to improve treatments for neuroblastoma – one of the most common and deadly types of childhood cancer. We have begun preparing for a second phase of our project which will investigate possible treatments for other types of tumors that occur in children. There are several new developments in the project, each of which increases its scope, potential effectiveness and eventual benefit for some of the most vulnerable pediatric patients.

    New project structure

    Phase 1 of HFCC was a joint effort by personnel at the Chiba Cancer Center Research Institute (which I formerly led) and Chiba University, (led by Dr. Hoshino and Dr. Tamura). Because of my new position, primary responsibility for the project is now shifting to the Saga Medical Center KOSEIKAN Research Institute (which I now lead). Phase 2 will also welcome several new collaborators, including teams from Hong Kong University (led by Dr. Godfrey C.F. Chan) and Texas Children’s Hospital (led by Dr. Ching C. Lau), both of whom are pediatric oncologists.

    New disease targets

    With the success of HFCC Phase 1 in identifying promising candidates for neuroblastoma, we are applying our proven research approach to considerably expand the scope of our work. In Phase 2, we will be examining a wider range of target childhood cancers, to include not only neuroblastoma but also other cancers in the nervous system, bones and liver. Our initial efforts in Phase 2 will target hepatoblastoma, neuroblastoma and Ewing’s sarcoma. Other cancers will be added later as specific protein targets are identified and their structures discovered.

    New therapy options

    Our move to Saga Medical Center KOSEIKAN means we also have access to the resources of the Saga International Heavy Charged Particle Cancer Therapy Foundation. This includes the use of heavy carbon ion beam radiotherapy, which could be indicated as one of the new radiotherapeutic strategies against childhood tumors like neuroblastoma. The combination of new drugs—like those discovered during HFCC Phase 1—and new radiotherapy shows great promise in helping children to conquer neuroblastoma in the future.

    New drug development partners

    In a previous update, one of the problems we mentioned is that many pharmaceutical companies are not interested in developing drugs for neuroblastoma, because the potential market is relatively small. That’s why we are especially excited to announce that recently, two organizations that support drug development in Japan – the National Institute of Biomedical Innovation (NIBIO) and the Innovation Network Corporation of Japan (INCJ) – have shown interest in our project of TrkB antagonists as candidate anti-cancer drugs. In addition, the Association Hubert Gouin: Enfance & Cancer, which supports researchers who develop new drugs against high-risk neuroblastoma, is also interested in our TrkB antagonists project. We hope to secure their support for our project in the near future.

    Once again, thank you to the thousands of volunteers who have made our work possible. We’re very excited to share these promising developments, and look forward to launching Phase 2 in the near future.

    See the full article here.

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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.

    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


    “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-
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers

    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


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

    IBM – Smarter Planet

  • richardmitnick 9:22 am on November 12, 2015 Permalink | Reply
    Tags: , Cancer,   

    From Stanford: “Researchers develop molecular target for brain cancer” 

    Stanford University Name
    Stanford University


    November 11th, 2015
    Jennifer Huber


    About 23,000 new cases of brain and central nervous system tumors are diagnosed annually, and more than 15,000 patients are expected to die of brain cancer this year in the United States, according to the American Cancer Society. Glioblastoma multiforme is the most common brain malignancy, but it remains incurable with only 5 percent of patients surviving at least 5 years after diagnosis. This bleak scenario has motivated the search for a better molecular target for glioblastoma multiforme diagnosis and therapy.

    Weibo Cai, PhD, an associate professor of radiology and medical physics, and his research team at the University of Wisconsin-Madison searched the Cancer Genome Atlas database and identified an effective biomarker for the deadly glioblastoma multiforme: the CD146 gene, which is highly active in glioblastoma.

    CD146 genes place unique CD146 proteins on the surface of cells. Cai’s team developed an antibody that selectively latches onto the CD146 proteins concentrated on the glioblastoma tumors. They also tagged the antibody with a radioactive copper isotope, so the tumors could be easily identified and localized with a positron emission tomograph (PET), an imaging scanner commonly used to detect cancer.

    Cai tested their antibody by implanting animal models with human glioblastoma tumors, injecting them with the antibody and imaging them with a small animal PET scanner. The copper-labeled antibody preferentially accumulated in the tumors, allowing PET imaging to accurately identify tumors as small as 2 mm. Their study results were recently reported in the Proceedings of the National Academy of Sciences.

    As Cai explained in a university news release:

    We’ve created a tag that – at least in our mouse model – is highly specific for this aggressive brain cancer. If the technique proves out in further tests, it could be used to diagnose some strains of aggressive glioblastoma, and also to evaluate treatment progress or even to test potential drugs.

    The researchers also found high activity of CD146 in ovarian, liver, and lung tumors so their antibody could have a wide range of applications. However, there is a lot of research to be done before the technique could be used in the clinic. Cai said in the news release, “This targets tumors with the worst survival, but I want to emphasize that human trials are some years in the future.”

    See the full article here .

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    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 11:56 am on November 3, 2015 Permalink | Reply
    Tags: , Cancer,   

    From MIT: “Tackling cancer research from multiple perspectives” 

    MIT News

    November 2, 2015
    Catherine Curro Caruso

    Tushar KamathPhoto: Bryce Vickmark

    Graduate student Tushar Kamath takes an interdisciplinary approach to cancer research.

    As an MIT undergraduate, Tushar Kamath regularly rode his bike across the Charles River to Massachusetts General Hospital (MGH) to retrieve blood samples from cancer patients; he then analyzed these samples on campus, at the Koch Institute for Integrative Cancer Research. Kamath, who received his BS in biological engineering in June and is now an MIT master’s student in biological engineering, says his trips back and forth across the river reflect his interdisciplinary view of research.

    “You’ve got the top physicians sitting across the river, and you’ve got the top scientists sitting on this side of the river,” Kamath says. “Everybody is so close together, the potential for collaboration is huge.”

    The blood that Kamath pedaled back from MGH helped in an exciting discovery about circulating tumor cells, which move through the blood in very low numbers, making them difficult to capture: He determined that a method of capturing these cells, developed in the lab where he was working, was as good as the method approved by the Food and Drug Administration. The experience showed Kamath that you don’t need a PhD to make a significant discovery.

    “It’s democratic in that anybody can really push forward and make these discoveries,” Kamath says, “as long as they have the knowledge base, the intuition, and the drive.”

    Kamath first experienced MIT the summer before his senior year of high school, at Thomas Jefferson High School for Science and Technology in Alexandria, Virginia. That summer, he spent two weeks at the Institute, working in a cancer-modeling lab where he is now working on his master’s degree. The experience not only put MIT on his radar, but also sparked what has become a long-term interest in cancer research.

    Multidisciplinary research

    Kamath is working with William Thilly, a professor of biological engineering at MIT, and research scientist Elena Gostjeva in the new field of metakaryotic biology. Gostjeva discovered the metakaryotic stem cells, which create organs during fetal and juvenile growth, but later serve as the generative stem cells for pathologic lesions including tumors and atherosclerotic plaques. These cells also have peculiarities including X-ray resistance, not using mitosis to divide, and organizing their genomes in a set of circular structures instead of in linear chromosomes.

    Kamath describes a cancer-modeling paper he co-authored that combined data from lab experiments on cancerous mutations in colonic stem cells with a large database of cancer mortality statistics. “I think that’s a very strong interdisciplinary effort because it does modeling of epidemiology from a huge perspective and then it also goes down into the very, very small single-cell level in the lab,” Kamath says.

    Kamath turns to his mentor for advice on everything from experimental design to medical school applications, and he has adopted Thilly’s interdisciplinary approach. Kamath’s current work tests drugs that could be inhibitors of genome-doubling metakaryotic cancer stem cells. He is testing inhibitors of a specific DNA polymerase used in metakaryotic stem cells but not needed in the mitotic eukaryotic cells generally studied in human biology.

    Kamath is now applying to MD/PhD programs, and would ultimately like to run a lab in a research hospital, so he can use the knowledge gained working with patients to inform experiments on new therapies. “There’s this yawning gap between the clinic and the lab bench, which can be bridged by those in an MD/PhD program, and I think it’s really where I want to start out as a career,” Kamath says.

    Getting multiple perspectives

    Kamath’s interdisciplinary approach also applies to other areas of his life. He began writing for MIT’s student newspaper, The Tech, during his freshman year; during his senior year, he served as executive editor. Kamath says he is proud of stories the paper produced on difficult topics, such as mental health and sexual assault, during his tenure.

    Kamath also spent a summer working on health care policy in U.S. Rep. Paul Ryan’s office as part of the MIT Washington Summer Internship Program. The experience provided him with insight into health care funding — and showed him that bipartisan compromise occurs much more often than he had realized. “I don’t think I will ultimately work in policy, but it is a good perspective,” Kamath says.

    As a graduate student, Kamath devotes time to mentoring undergraduates in biological engineering — which he sees as an important role for any scientist. “Advising and mentoring … is very high-impact, and it’s something most scientists should try to do in their career, because they can help bring up a new generation,” he says.

    See the full article here .

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    The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

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  • richardmitnick 1:08 pm on October 22, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From MIT: “Biologists unravel drug-resistance mechanism in tumor cells” 

    MIT News

    October 22, 2015
    Anne Trafton | MIT News Office

    P53, which helps healthy cells prevent genetic mutations, is missing from about half of all tumors. Researchers have found that a backup system takes over when p53 is disabled and encourages cancer cells to continue dividing. In the background of this illustration are crystal structures of p53 DNA-binding domains. Image: Jose-Luis Olivares/MIT (p53 illustration by Richard Wheeler/Wikimedia Commons)

    Targeting the RNA-binding protein that promotes resistance could lead to better cancer therapies.

    About half of all tumors are missing a gene called p53, which helps healthy cells prevent genetic mutations. Many of these tumors develop resistance to chemotherapy drugs that kill cells by damaging their DNA.

    MIT cancer biologists have now discovered how this happens: A backup system that takes over when p53 is disabled encourages cancer cells to continue dividing even when they have suffered extensive DNA damage. The researchers also discovered that an RNA-binding protein called hnRNPA0 is a key player in this pathway.

    “I would argue that this particular RNA-binding protein is really what makes tumor cells resistant to being killed by chemotherapy when p53 is not around,” says Michael Yaffe, the David H. Koch Professor in Science, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study, which appears in the Oct. 22 issue of Cancer Cell.

    The findings suggest that shutting off this backup system could make p53-deficient tumors much more susceptible to chemotherapy. It may also be possible to predict which patients are most likely to benefit from chemotherapy and which will not, by measuring how active this system is in patients’ tumors.

    Rewired for resistance

    In healthy cells, p53 oversees the cell division process, halting division if necessary to repair damaged DNA. If the damage is too great, p53 induces the cell to undergo programmed cell death.

    In many cancer cells, if p53 is lost, cells undergo a rewiring process in which a backup system, known as the MK2 pathway, takes over part of p53’s function. The MK2 pathway allows cells to repair DNA damage and continue dividing, but does not force cells to undergo cell suicide if the damage is too great. This allows cancer cells to continue growing unchecked after chemotherapy treatment.

    “It only rescues the bad parts of p53’s function, but it doesn’t rescue the part of p53’s function that you would want, which is killing the tumor cells,” says Yaffe, who first discovered this backup system in 2013.

    In the new study, the researchers delved further into the pathway and found that the MK2 protein exerts control by activating the hnRNPA0 RNA-binding protein.

    RNA-binding proteins are proteins that bind to RNA and help control many aspects of gene expression. For example, some RNA-binding proteins bind to messenger RNA (mRNA), which carries genetic information copied from DNA. This binding stabilizes the mRNA and helps it stick around longer so the protein it codes for will be produced in larger quantities.

    “RNA-binding proteins, as a class, are becoming more appreciated as something that’s important for response to cancer therapy. But the mechanistic details of how those function at the molecular level are not known at all, apart from this one,” says Ian Cannell, a research scientist at the Koch Institute and the lead author of the Cancer Cell paper.

    In this paper, Cannell found that hnRNPA0 takes charge at two different checkpoints in the cell division process. In healthy cells, these checkpoints allow the cell to pause to repair genetic abnormalities that may have been introduced during the copying of chromosomes.

    One of these checkpoints, known as G2/M, is controlled by a protein called Gadd45, which is normally activated by p53. In lung cancer cells without p53, hnRNPA0 stabilizes mRNA coding for Gadd45. At another checkpoint called G1/S, p53 normally turns on a protein called p21. When p53 is missing, hnRNPA0 stabilizes mRNA for a protein called p27, a backup to p21. Together, Gadd45 and p27 help cancer cells to pause the cell cycle and repair DNA so they can continue dividing.

    Personalized medicine

    The researchers also found that measuring the levels of mRNA for Gadd45 and p27 could help predict patients’ response to chemotherapy. In a clinical trial of patients with stage 2 lung tumors, they found that patients who responded best had low levels of both of those mRNAs. Those with high levels did not benefit from chemotherapy.

    “You could measure the RNAs that this pathway controls, in patient samples, and use that as a surrogate for the presence or absence of this pathway,” Yaffe says. “In this trial, it was very good at predicting which patients responded to chemotherapy and which patients didn’t.”

    “The most exciting thing about this study is that it not only fills in gaps in our understanding of how p53-deficient lung cancer cells become resistant to chemotherapy, it also identifies actionable events to target and could help us to identify which patients will respond best to cisplatin, which is a very toxic and harsh drug,” says Daniel Durocher, a senior investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, who was not part of the research team.

    The MK2 pathway could also be a good target for new drugs that could make tumors more susceptible to DNA-damaging chemotherapy drugs. Yaffe’s lab is now testing potential drugs in mice, including nanoparticle-based sponges that would soak up all of the RNA binding protein so it could no longer promote cell survival.

    See the full article here .

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    The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

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  • richardmitnick 8:53 am on October 20, 2015 Permalink | Reply
    Tags: , Cancer, Melanoma,   

    From Weizmann: “Melanoma Mutations Mapped” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    No Writer Credit

    Cancer is a disease that begins with gene alterations: At the high end of the mutation scale, a cancer such as melanoma has hundreds. That may be why melanoma drugs that block certain cancer-causing genes only work for a subset of patients, and even these are successful for just a short while. Better maps might help in navigating the complex routes that mutations chart in cancer cells. To this end, a giant consortium of scientists has been working on the Cancer Genome Atlas, a project overseen by the US National Institutes of Health, to plot the maps of a number of cancer genomes.

    Prof. Yardena Samuels

    Prof. Yardena Samuels of the Weizmann Institute’s Molecular Cell Biology Department is a part of the Cancer Atlas group that recently produced the melanoma genome map. Hundreds of researchers from Australia, the US, Canada, Russia, Germany, Italy, Poland, China and Korea participated in the effort. “This has been the most in-depth mapping yet,” says Samuels. After a careful selection process, 333 melanoma samples were included in the study, and the screening was conducted using six different platform technologies, going beyond the bounds of simple gene sequencing to explore how the various genes are expressed, how they interact and which proteins they produce.

    Each sample required a second, non-cancerous sample from the same patient for comparison, and several of the samples afforded comparisons of genes from the patients’ early tumors to those that had metastasized. In addition to the sequencing of protein-coding genes, some of the samples had their entire genome sequenced, which could prove in the future to be an “unexplored goldmine of information on what makes cancer tick,” says Samuels. RNA and microRNA, as well as protein expression assays, were included. The latter screens added further dimensions to the gene map – creating a “landscape” that can help researchers understand not just the genes, but the pathways, intersections and cancer-causing diversions associated with them.

    “The study was intensive, and it has paid off,” says Samuels. For one thing, it showed, for the first time, that melanomas can be divided into four distinct groups, according to a main mutation. Now melanoma researchers will be able to focus on understanding exactly how the different mutations lead to cancer, and physicians may eventualy gain better tools for diagnosing the disease and tailoring treatments to individual cases. The first type, occurring in a mutation “hotspot,” is known as BRAF, and it tends to appear in younger people, in whom the cancer is fairly aggressive. The second is known as RAS. BRAF and RAS protein products lie in the same pathway so that BRAF and RAS mutations are mutually exclusive: A patient will have one or the other, but not both. The third is called NF1, and this mutation was found in older patients. The fourth group, called triple wild type, had none of the three most common mutations.

    Metastatic melanoma cells. Image: NIH

    In addition, the in-depth analysis held a surprise finding. RNA and protein expression tests revealed the infiltration of immune cells called lymphocytes into the tumors. These turned out to be highly correlated with the patient’s prognosis – the more lymphocytes, the better their chances of surviving, regardless of the genetic signature of their melanoma cells. This finding has interesting implications for the field of cancer immunotherapy, in which a patient’s immune cells are “trained” to fight the cancer. It suggests that even upping the numbers of particular immune cells could have a positive effect, and it could help identify those patients who might benefit from various new immunotherapies.

    Another area of research arising from the new cancer genome that could bear fruit in the near future is a sort of “matching” of existing drug compounds to the genetic profiles. For example, a comparison of genomes from different cancers shows that the genetic mutation pattern of one type of melanoma is similar to that of a form of a brain cancer called glioblastoma. That means that drugs already on the market for glioblastoma might have an effect on melanoma as well.

    Separating the drivers from the passengers

    Samuels says she intends to continue adding detail to the map – her lab has its own bank of melanoma cells, and she is creating an expanded database of melanoma genomes. This melanoma cell bank is an important resource for her lab, where she and her group are working to figure out which of the many mutated genes drive the development of melanoma, which help the drivers “steer,” and which are just “passengers.” Experiments on cell lines from the bank, for example, enable the group to investigate the effects of individual genes, and they are going after are suspected drivers, as well as the “helpers.”

    In parallel, she is beginning to explore the pathways – the series of biological interactions that underlie each action in the cell – in two of the melanoma subgroups. “If the mutation in a gene, for example, a tumor suppressor, causes a loss of function, you can’t fix it by blocking the gene – the problem is that the gene is not working in the first place,” she says. “But if you follow the pathway, you are likely to find other genes that present targets for turning the pathway around, farther down the line.

    “We are entering a new era of precision medicine in melanoma, in which physicians will aim to determine the personal profile of each cancer and tailor the treatment accordingly,” she says

    Prof. Yardena Samuels’ research is supported by the Ekard Institute for Diagnosis, which she heads; the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Laboratory in the name of M.E.H. Fund established by Margot and Ernst Hamburger; the Louis and Fannie Tolz Collaborative Research Project; the Dukler Fund for Cancer Research; the European Research Council; the De Benedetti Foundation-Cherasco 1547; the Peter and Patricia Gruber Awards; the Comisaroff Family Trust; the Rising Tide Foundation; the estate of Alice Schwarz-Gardos; the estate of John Hunter; the Estate of Adrian Finer. Prof. Samuels is the incumbent of the Knell Family Professorial 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 9:49 am on October 19, 2015 Permalink | Reply
    Tags: , Cancer,   

    From COSMOS: “New hope for cancer medicine” 

    Cosmos Magazine bloc


    19 Oct 2015
    Viviane Richter

    Leukaemia patient Emma Whitehead’s life was saved by an experimental treatment that reprogrammed her own T cells to attack her cancer.Credit: Jeff Swensen / The New York Times

    Researchers have found a way to fine-tune treatments that use a patient’s own immune system to attack cancer.

    Reprogramming the body’s immune cells to fight cancer tumours saves lives, but it can backfire. The treatment, called immunotherapy, can be deadly if these reprogrammed cells attack the wrong target inside a patient’s body. So researchers at the University of California in San Francisco, led by Wendell Lim, have designed a molecular safety switch to keep them on a tight leash.

    Richard Boyd, an immunologist at Melbourne’s Monash University, calls the idea “brilliant. The science is very slick.”

    In 2013, immunotherapy rescued seven-year-old Emma Whitehead. She was diagnosed with leukaemia at age five and had relapsed after multiple rounds of chemotherapy. Her doctors, who were running out of options, put her forward for an experimental therapy.

    Cancer kills because it can be very good at evading the immune system. Whitehead’s doctors extracted some of her T cells (a type of white blood cell essential for human immunity), genetically engineered them to recognise her cancer and then re-injected them into her body.

    These engineered cells are known as chimeric antigen receptor (CAR) T cells. They are equipped with precision tumour-targeting equipment, consisting of two main parts. The first is a protein that works somewhat like a barcode scanner – it can recognise cancer cells by identifying the proteins and sugars found on their surface. The scanner is hooked up to the second component – a switchboard inside the cell that, once it receives an alarm signal from the scanner, puts the cell on the attack.

    Like T cells, CAR-T cells can roam the body for months or longer, allowing them to make a sustained attack on cancer cells. But their longevity also poses a problem if the treatment goes awry. “The problem is that you put them in and then you can’t do anything,” says Lim.

    When T cells attack, they release small molecules called cytokines – messengers that recruit more immune cells. But if the immune response triggered by the CAR-T cells is too powerful, the resulting “cytokine storm” can cause potentially fatal fevers. Emma Whitehead nearly died from the fevers that followed her treatment, before making a full recovery.

    Killer T cells (green and red) surrounding a cancer cell. Lim’s re-engineered T cells hunt down cancer cells extremely efficiently – and now come with a kill switch should the treatment go awry.Credit: Alex Ritter, Jennifer Lippincott Schwartz, Gillian Griffiths/National Institutes of Health

    Another potential problem is “cross reactivity”. This occurs when a normal healthy cell produces a protein or sugar that is similar to the cancer markers the CAR-T cells have been primed to recognise. This can cause the CAR-T cells to attack normal tissues by mistake.

    So Lim’s team designed a control switch.

    “It’s really pretty simple,” he says. They genetically engineered CAR-T cells to carry the barcode scanner and switchboard as two separate parts, so they can scan and stick to the target but can’t attack the cell. Only when a special glue is added – in this case, a drug called rapalog – do the parts snap together, completing the circuit and allowing the cell to launch an offensive. By withdrawing the drug doctors can switch off the T cells if things go awry.

    Lim’s team found the “switchable” CAR-T cells only killed cancer cells in mice when the mice were also given rapalog. In a petri dish, they also showed they could use rapalog to dial the CAR-T cells up or down like a dimmer switch. The more rapalog, the more cancer cells died.

    Doctors could one day inject these switchable CAR-T cells to let them roll around the body and “hope they stick to cancer cells like flies on a cake,” as Boyd puts it. Doctors could then slowly ramp up their cancer-killing power by increasing the rapalog dose, while keeping a close eye on any side effects. Should they see excessive fever or signs of cross-reactivity, doctors could stop and the T cells would become inactive. Rapalog is excreted by the body after only a few hours.

    “We’re very excited,” says Lim. “We weren’t sure if we could get this kind of tuneable control but we’ve really shown we can. And that could really help move this therapy forward – right now.”

    Lim’s next step is to find a better, longer-lasting glue so an effective dose can be sustained. Rapalog is excreted a little too fast for a practical treatment.

    Boyd says he is optimistic about the place of CAR-T cells in a wide range of new cancer therapies: “The immune system is remarkably sophisticated and it’s going to be the smartest way to treat disease.”

    See the full article here .

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  • richardmitnick 6:28 am on October 13, 2015 Permalink | Reply
    Tags: , , Cancer   

    From AAAS: “Cancer Research UK announces grand challenges competition” 



    A blood vessel within a melanoma (brown) is part of the tumor microenvironment, one area targeted by Cancer Research UK’s Grand Challenges.K. Hodivala-Dilke & M. Stone, Wellcome Images

    11 October 2015
    Jocelyn Kaiser

    A £20 million grant awaits a team of researchers who submit the best proposal for tackling one of seven grand challenges in cancer.

    The new competition, announced today by Cancer Research UK, the giant U.K. research charity, is meant to spur collaborations aimed at exploring untested but promising ideas. “They’re willing to take some risks and see some projects fail,” says advisory board member Brian Druker of Oregon Health & Science University in Portland, who helped develop Gleevec, a model for drugs targeted at molecular defects in cancers. The charity expects to spend £100 million on the program over the next 5 years through a series of 5-year grants.

    The challenges were developed over the past few months by Druker and other advisers. The list includes mapping the cells and molecules within tumors, or the microenvironment; devising drugs that target MYC, a gene involved in many cancers; eradicating cancers caused by Epstein-Barr virus, a major cause of certain cancers in East Asia; and developing vaccines to prevent nonviral cancers.

    These areas have been studied before, but haven’t had enough resources or the science hasn’t been ripe enough, says Nic Jones, chief scientist for the charity. For example, recent insights into how tumors evade the immune system that led to several new drugs could shed light on vaccines that prevent tumors from growing in the first place. “You could imagine how powerful that could be,” Jones says. Team members may come from both academia and industry and must include U.K. researchers.

    The U.K. effort brings to mind Stand Up to Cancer (SU2C), a Hollywood-backed fundraising effort that has put millions of dollars into large research “dream teams” since 2008. It is also in line with Provocative Questions, a U.S. National Cancer Institute (NCI) project to identify neglected questions in cancer launched in 2010 by then-Director Harold Varmus. But the Cancer Research UK grants will be an order of magnitude larger than the NCI grants and address more fundamental questions than projects funded by SU2C, which are supposed to lead to a clinical trial within 3 years.

    Cancer Research UK won’t mind if some researchers complain about what’s not on the list of challenges, Druker says. “If part of what this does is stimulate a debate, that’s a good thing.”

    Teams that fail to win the challenge may seek funding from other programs at Cancer Research UK or elsewhere, Jones says. The losers could also try again if their proposal addresses a challenge that remains on the list of eligible topics, which will be updated annually.

    Preproposals for the first round are due in February. The winning team will be announced next fall.

    See the full article here .

    The American Association for the Advancement of Science is an international non-profit organization dedicated to advancing science for the benefit of all people.

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  • richardmitnick 10:48 am on October 11, 2015 Permalink | Reply
    Tags: , Cancer,   

    From UC Davis: “New treatments a big step for patients with advanced kidney cancer” 

    UC Davis bloc

    UC Davis

    September 29, 2015
    Dorsey Griffith
    Phone: 916-734-9118

    In an editorial published in the New England Journal of Medicine, Primo Lara, associate director for Translational Research at the UC Davis Comprehensive Cancer Center and David Quinn, medical director, USC Norris Cancer Hospital, highlight two new drugs that have shown great efficacy against kidney cancer. In two studies, also published in the Sept. 25 edition of the journal, researchers showed that nivolumab, an immunotherapeutic drug, and cabozantinib, a multikinase inhibitor, are more effective against advanced kidney cancer than a current standard of care. In the accompanying editorial, Lara and Quinn note that the positive results are “unequivocal.”

    Primo Lara

    “These new drugs are clearly better than the older drug everolimus; they will soon find their place in the kidney cancer arsenal,” notes Lara. “Since these new agents are already approved for other indications, it is likely that their manufacturers will be applying to get FDA approval for kidney cancer soon.”

    Currently, kidney cancer patients are first treated with an angiogenesis inhibitor, which restricts or reduces blood vessel growth into tumors. When that that therapy ceases to be effective patients are sometimes switched to everolimus, which inhibits mTOR, a master protein that controls a number of important cell growth pathways.

    In the nivolumab study, called Checkmate, the median overall survival for patients treated with nivolumab was 25 months, compared to 19.6 months for those on everolimus. In addition, nivolumab reduced the risk of death by 27 percent and had far fewer side effects. Nivolumab is a checkpoint inhibitor, which takes the brakes off T-cells to help the immune system attack cancer. The drug is currently approved to treat advanced squamous cell lung cancer and metastatic melanoma.

    In the cabozantinib study, called METEOR, the drug improved progression-free survival by nearly four months and showed a strong trend to improving overall survival. Cabozantinib is a multi-kinase inhibitor that affects several proteins associated with cancer progression and is currently approved to treat medullary thyroid cancer.

    While these results are encouraging, the editorial noted some important caveats. Both trials failed to produce a significant number of complete responses, in which the cancer disappeared completely. There are also no good biomarkers that predict benefit from these agents.

    “We need to expand the spectrum benefit by finding a biomarker that predicts which patient will preferentially benefit,” said Lara. “There seems to be a fixed number of patients who respond to immunotherapy – about 20 to 30 percent. We need to find markers that identify these patients. We also need to develop new combinations that broaden the group that benefits.”

    The editorial also highlights another issue – value. These drugs are quite expensive, and the authors express their concerns that some patients will not have access due to inability to afford these pricey medicines.

    “No treatment will work if patients do not get it,” said Lara. “And no patient will get it if it’s not affordable.”

    Lara was a compensated member of the Independent Data Monitoring Committee for the METEOR trial.

    See the full article here .

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    The University of California, Davis, is a major public research university located in Davis, California, just west of Sacramento. It encompasses 5,300 acres of land, making it the second largest UC campus in terms of land ownership, after UC Merced.

  • richardmitnick 7:24 am on October 10, 2015 Permalink | Reply
    Tags: , Cancer,   

    From The Conversation: “Chemistry Nobel DNA research lays foundation for new ways to fight cancer” 

    The Conversation

    October 8, 2015
    Rachel Litman Flynn

    You’d be in bad shape if your cells couldn’t fix DNA issues that arise. redondoself, CC BY

    Our cells are up against a daily onslaught of damage to the DNA that encodes our genes. It takes constant effort to keep up with the DNA disrepair – and if our cells didn’t bother to try to fix it, we might not survive. The DNA damage repair pathways are an essential safeguard for the human genome.

    The 2015 Nobel Laureates in chemistry received the prize for their pioneering work figuring out the molecular machinery that cells use to repair that DNA damage. In their basic research, Tomas Lindahl, Paul Modrich and Aziz Sancar each narrowed in on one piece of the DNA repair puzzle.

    They’ve laid the framework for the research that many basic and translational scientists are expanding upon to try to crack cancer. Ironically, we’re finding ways to turn that DNA repair system against cancerous cells that have often arisen from DNA damage in the first place.

    UV light from the sun is one cause of DNA mutations. NASA/David Herring, CC BY

    DNA under siege

    DNA is composed of four simple letters, or nucleotides, A, T, C and G. When combined, these nucleotides form the genetic code. There are approximately 30,000 genes in the human genome.

    Each time a cell grows and divides, every single gene needs to be faithfully copied to the next generation of cells. This process of DNA replication is constantly threatened by both internal and external sources of DNA damage. There are environmental sources such as radon from the earth or UV light from the sun. Or it can be just a mistake, happening within the cell as a consequence of normal growth and division. Some studies have estimated that a single cell can experience several thousand DNA damage events in a single day.

    The question then becomes: how does the cell repair all of this damage? Or perhaps more worrisome, what happens if the cell doesn’t repair the damage?

    A full toolbox to deal with the damage

    To counter the daily onslaught of DNA damage, mammalian cells have evolved a number of intricate mechanisms to not only recognize DNA damage, but repair it and restore the original genetic sequence.

    Consider a typo that changes the letter N to the letter M, causing “grin” to become “grim.” That single typo has now changed the entire meaning of the word. It works just the same in the “words” of the genetic code when an incorrect nucleotide takes the place of the right one. The DNA damage repair enzymes function like an eraser reverting the mutant M back to the original N.

    DNA excision repair gets rid of a mistaken nucleotide and fills in what should be there. LadyofHats

    Following DNA damage, the cell must first recognize the damage and then alert the system that there’s a problem. The recognition machinery then activates various factors to halt cell growth until the damage has been repaired. And if things are too far gone, additional factors are poised and ready to induce cell death.

    That’s the most basic way to think about the DNA damage response pathway, as a simple chain of events. Of course it’s a lot more complicated, a complex network of checks and balances to ensure that the DNA damage is not only recognized but clearly identified to ensure that the correct factors are recruited to repair the lesion.

    Much like a homeowner wouldn’t want an electrician to fix the leaky roof, a DNA “typo” shouldn’t be fixed by a mechanism used to heal double-strand DNA breaks, for instance. Therefore, sensing which specific genetic lesion is the problem is one of the earliest and most critical steps in the DNA damage response pathway.

    It’s hard to say exactly how many DNA damage response “sensors” there are or exactly who they are, but that’s something the field is actively investigating. Likewise, while the number of DNA damage repair pathways we know about hasn’t necessarily increased since the groundbreaking Nobel work was done, the complexity of our understanding has.

    What if the repair process itself is broken?

    In a limited capacity, mutations actually aid evolution. There have to be changes for natural selection to act on, so these DNA mutations are a significant factor in Darwin’s theory of evolution. However, what is a blessing may also be a curse.

    Mutations in essential genes can lead to death even before we enter the world. However, mutations in nonessential genes may not be evident until later in life. When these mutations persist – or even worse, accumulate – it can lead to genomic instability. And that’s a hallmark of cancer cells.

    You can imagine, then, that a single mutation in a component of the DNA damage response pathway could lead to the accumulation of DNA damage, genomic instability and ultimately the progression toward cancer. And it’s true, we frequently find mutations in the DNA damage response pathway in cancer. Deciphering exactly how these pathways work is essential to our understanding not only of cancer, but also of how we might exploit these pathways to actually treat the disease.
    Harnessing the repair systems to our own ends

    These damage repair pathways are essential to prevent the accumulation of genetic lesions and ultimately inhibit the progression toward cancer. Is there a way we can exploit the system, push it over the edge and cause an unwanted cell not just to gain mutations but to die?

    To that end, researchers are hard at work trying to further define the nitty gritty details that regulate the DNA damage response. Others are trying to identify factors that we could target therapeutically.

    It may seem counterintuitive to target the DNA damage response pathway once it’s already been inactivated by a mutation. But the approach has its advantages.

    Generally, when a genetic mutation inactivates one branch of repair, the cell will try to compensate by using another type of repair just to keep the cell alive. Would you rather call the electrician and hope he can fix the leaky roof or risk having the entire roof collapse in on you?

    The cell opts for a back-up mechanism to try to resolve the damage. In general, this results in inadequate repair and the acquisition of additional mutations, fueling the genomic instability and cancer progression.

    We want to eliminate the back-up mechanism – send the electrician out of town. Research has demonstrated that when one type of repair mechanism is inactivated by a genetic mutation and you therapeutically inactivate the back-up mechanism, the cancerous cell dies. Likewise, if we combine drugs that induce a particular type of damage and then inactivate that specific repair pathway, cells die. Clinical scientists have demonstrated that this can lead to tumor regression in patients sparking a surge of research in this area.

    In these dividing cells, DNA is colored white. They were treated with ATR molecules that interfere with DNA damage repair. Dr Neil J Ganem, Boston University, CC BY-ND

    Targeting telomeres

    My lab is interested in understanding how the DNA damage response is regulated specifically at telomeric DNA.

    The telomere is a repetitive DNA sequence that caps the ends of each human chromosome. Telomeres function as a barrier, protecting the human genome from degradation and/or the fusion of whole chromosomes.

    Each time a cell divides, a portion of this barrier is lost; over time the shortened telomere compromises the genome’s stability. To avoid damage to the genome, critically short telomeres send a signal to the cell to either stop growing or induce cell death.

    Cancer cells, however, have evolved mechanisms to overcome progressive telomere shortening and bypass this growth arrest. In other words, they outmaneuver the normal routine, dividing and growing while avoiding the usual step of telomere shortening that eventually leads to death for normal cells. One way they counter telomere shortening and promote telomere elongation is by activating the Alternative Lengthening of Telomeres pathway (ALT).

    The ALT mechanism is active in 10%-15% of all human cancers. This incidence skyrockets to approximately 60% in some of the most aggressive forms of human cancer, including osteosarcoma and glioblastoma. These cancers are often resistant to common therapeutic strategies and there are no therapies that specifically target the ALT pathway.

    Representative chromosome spread from ALT cells where telomeres are stained with either a red or green probe. A yellow signal indicates a ??? [not complete]

    In my lab, we’re focusing on one of the molecules that senses DNA damage in the first place, the ATR kinase. We’ve found that preventing it from doing its job leads to both a decrease in recombination at telomeres and an increase in telomere loss at the chromosome ends, suggesting a defect in ALT activity.

    Perhaps most significant is that ATR inhibitions led to catastrophic cell division and robust cell death in ALT-positive cancer cells, yet had little effect on non-cancerous cell lines.

    These studies may allow us to drive ATR inhibitors into preclinical development with the ultimate goal of improving the therapeutic strategies in the treatment of some of the most aggressive forms of human cancer.

    Time-lapse live-cell imaging experiment from the author’s lab investigating how to disrupt cancer cells by disrupting telomere maintenancete.
    download the mp4 video here.

    It’s this kind of translational research that builds on the framework laid by the work of our newest Nobel laureates in chemistry. Their basic research is proving to be the foundation for new ways to target – and hopefully treat – cancer.

    See the full article here .

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    The Conversation US launched as a pilot project in October 2014. It is an independent source of news and views from the academic and research community, delivered direct to the public.
    Our team of professional editors work with university and research institute experts to unlock their knowledge for use by the wider public.
    Access to independent, high quality, authenticated, explanatory journalism underpins a functioning democracy. Our aim is to promote better understanding of current affairs and complex issues. And hopefully allow for a better quality of public discourse and conversation.

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