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  • richardmitnick 5:19 pm on July 25, 2016 Permalink | Reply
    Tags: , Cancer, ,   

    From MIT: “Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results” 

    MIT News
    MIT News
    MIT Widget

    July 25, 2016
    Helen Knight

    1
    Researchers at MIT are developing an adhesive patch that can stick to a tumor site, either before or after surgery. The patch delivers a triple-combination of drug, gene, and photo (light-based) therapy via specially designed nanospheres and nanorods, shown here attacking a tumor cell. Image: Ella Maru

    Approximately one in 20 people will develop colorectal cancer in their lifetime, making it the third-most prevalent form of the disease in the U.S. In Europe, it is the second-most common form of cancer.

    The most widely used first line of treatment is surgery, but this can result in incomplete removal of the tumor. Cancer cells can be left behind, potentially leading to recurrence and increased risk of metastasis. Indeed, while many patients remain cancer-free for months or even years after surgery, tumors are known to recur in up to 50 percent of cases.

    Conventional therapies used to prevent tumors recurring after surgery do not sufficiently differentiate between healthy and cancerous cells, leading to serious side effects.

    In a paper published today in the journal Nature Materials, researchers at MIT describe an adhesive patch that can stick to the tumor site, either before or after surgery, to deliver a triple-combination of drug, gene, and photo (light-based) therapy.

    Releasing this triple combination therapy locally, at the tumor site, may increase the efficacy of the treatment, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research.

    The general approach to cancer treatment today is the use of systemic, or whole-body, therapies such as chemotherapy drugs. But the lack of specificity of anticancer drugs means they produce undesired side effects when systemically administered.

    What’s more, only a small portion of the drug reaches the tumor site itself, meaning the primary tumor is not treated as effectively as it should be.

    Indeed, recent research in mice has found that only 0.7 percent of nanoparticles administered systemically actually found their way to the target tumor.

    “This means that we are treating both the source of the cancer — the tumor — and the metastases resulting from that source, in a suboptimal manner,” Artzi says. “That is what prompted us to think a little bit differently, to look at how we can leverage advancements in materials science, and in particular nanotechnology, to treat the primary tumor in a local and sustained manner.”

    The researchers have developed a triple-therapy hydrogel patch, which can be used to treat tumors locally. This is particularly effective as it can treat not only the tumor itself but any cells left at the site after surgery, preventing the cancer from recurring or metastasizing in the future.

    Firstly, the patch contains gold nanorods, which heat up when near-infrared radiation is applied to the local area. This is used to thermally ablate, or destroy, the tumor.

    These nanorods are also equipped with a chemotherapy drug, which is released when they are heated, to target the tumor and its surrounding cells.

    Finally, gold nanospheres that do not heat up in response to the near-infrared radiation are used to deliver RNA, or gene therapy to the site, in order to silence an important oncogene in colorectal cancer. Oncogenes are genes that can cause healthy cells to transform into tumor cells.

    The researchers envision that a clinician could remove the tumor, and then apply the patch to the inner surface of the colon, to ensure that no cells that are likely to cause cancer recurrence remain at the site. As the patch degrades, it will gradually release the various therapies.

    The patch can also serve as a neoadjuvant, a therapy designed to shrink tumors prior to their resection, Artzi says.

    When the researchers tested the treatment in mice, they found that in 40 percent of cases where the patch was not applied after tumor removal, the cancer returned.

    But when the patch was applied after surgery, the treatment resulted in complete remission.

    Indeed, even when the tumor was not removed, the triple-combination therapy alone was enough to destroy it.

    The technology is an extraordinary and unprecedented synergy of three concurrent modalities of treatment, according to Mauro Ferrari, president and CEO of the Houston Methodist Research Institute, who was not involved in the research.

    “What is particularly intriguing is that by delivering the treatment locally, multimodal therapy may be better than systemic therapy, at least in certain clinical situations,” Ferrari says.

    Unlike existing colorectal cancer surgery, this treatment can also be applied in a minimally invasive manner. In the next phase of their work, the researchers hope to move to experiments in larger models, in order to use colonoscopy equipment not only for cancer diagnosis but also to inject the patch to the site of a tumor, when detected.

    “This administration modality would enable, at least in early-stage cancer patients, the avoidance of open field surgery and colon resection,” Artzi says. “Local application of the triple therapy could thus improve patients’ quality of life and therapeutic outcome.”

    Artzi is joined on the paper by João Conde, Nuria Oliva, and Yi Zhang, of IMES. Conde is also at Queen Mary University in London.

    See the full article here .

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  • richardmitnick 4:46 pm on July 25, 2016 Permalink | Reply
    Tags: 3-D printing, , Cancer, ,   

    From U Wisconsin: “Tiny 3-D models may yield big insights into ovarian cancer” 

    U Wisconsin

    University of Wisconsin

    July 25, 2016
    Will Cushman
    perspective@engr.wisc.edu

    With a unique approach that draws on 3-D printing technologies, a team of University of Wisconsin–Madison researchers is developing new tools for understanding how ovarian cancer develops in women.

    About 1.5 percent of American women will be diagnosed with ovarian cancer, but most of them will not be diagnosed until late in the disease’s progression — after the cancer has spread to other parts of the body. This is reflected in the grim outlook for most women: The five-year survival rate for ovarian cancer is about 25 percent.

    Paul Campagnola, a professor of biomedical engineering and medical physics at UW–Madison, leads a group of researchers aiming to improve that outlook by understanding how ovarian cancer cells interact with nearby body tissue, and by developing new tools for imaging and detecting the disease. With a $2 million grant from the National Institutes of Health, they will use technology they’ve developed on the UW–Madison campus to develop images of tissues from surgical patients. The first target is collagen, a common protein that gives much of the body structure by holding bones, ligaments and muscles together.

    1
    A normal ovarian epithelial cell clings to a tiny model of an ovarian cancer tumor made with a 3-D printer. The tumor models will help scientists study ovarian cancer in mice, which do not naturally develop the disease. Image courtesy of Paul Campagnola

    “In most cancers, including ovarian, there are large changes in the collagen structure that goes along with the disease,” Campagnola says. “It might happen first. It might be later. It’s actually not known.”

    Campagnola and his colleagues, including Kevin Eliceiri, director of UW–Madison’s Laboratory for Optical and Computational Instrumentation, and Manish Patankar, associate professor of obstetrics and gynecology, hope to eliminate that unknown by printing tiny, 3-D models of the collagen samples.

    The models will be biomimetic — synthetic, but mimicking biological materials, as Velcro mimics the burs of a plant — and extremely small. Because, after seeding the models with ovarian cancer cells, the researchers will implant them into mice.

    Why not simply inject the mice with cancer cells and skip the painstaking imaging and 3-D printing process? Mice don’t get ovarian cancer — a partial answer for why we still don’t understand ovarian cancer as well as many other cancers.

    “The current way that people study ovarian cancer in a mouse is very poor,” Campagnola explains. “They just take human cell lines and then inject them into a mouse. Then some of them will form into a tumor, but most do not.”

    By implanting a 3-D tissue model seeded with ovarian cancer into mice, Campagnola hopes to mimic more closely the conditions of metastatic ovarian cancer in humans.

    “What’s different is our tissues will already be 3-D structured,” Campagnola says. “One problem when people study cancer sometimes is that they put cells in a dish. Cells in a dish don’t act like cells in tissue. So we’re trying to give them the tissue structure that cancer cells would have in a native environment.”

    From there, they’ll study how the implanted tumors grow inside the mice, and hopefully begin to learn more about the cues and processes involved in the disease’s progression and spread.

    It’s an approach that no one has ever attempted, one that will also help improve the way doctors make images of ovaries inside the body.

    “It’s an integrated approach to improving our imaging capabilities, but then also using our imaging capabilities to make these models so we can study the biology,” Campagnola says.

    Ultimately, the team’s long-term goal is to improve screening, diagnosis and treatment of ovarian cancer. One of the most effective ways to improve the outlook for women with ovarian cancer is to develop a straightforward method for screening women at higher risk for the disease. Women with a mutation in a gene called BRCA — a mutation also implicated in a higher risk for breast cancer — have a 40 percent chance of developing ovarian cancer in their lifetime.

    “Those are the women we really want to follow,” Campagnola says. “You could imagine — we’re a long way off from this — screening those women every few years with a minimally invasive device through a laparoscope or through the fallopian tubes.”

    But to get to that point, Campagnola says, researchers need to know a lot more about how ovarian cancer works.

    “You have to know what you’re looking for,” he says. “That’s why we have all this more basic work to do to get to that point. That’s why we need better imaging tools and we need better models to understand the biology of the disease.”

    See the full article here .

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  • richardmitnick 6:12 am on July 23, 2016 Permalink | Reply
    Tags: , Cancer,   

    From MIT: “Cancer-fighting bacteria” 

    MIT News
    MIT News
    MIT Widget

    July 20, 2016
    Anne Trafton

    1
    Researchers at MIT and the University of California at San Diego have delivered artificial genetic circuits into bacteria, allowing the microbes to kill cancer cells in three different ways. Here, an image of a motherboard has been micropatterned using programmable probiotic bacteria. The bright lines are composed of dots made of bacteria. This technique was developed in the lab of MIT professor Sangeeta Bhatia, who is a senior author on the new paper. Credit: Vik Muniz and Tal Danino

    Researchers at MIT and the University of California at San Diego (UCSD) have recruited some new soldiers in the fight against cancer — bacteria.

    In a study appearing in the July 20 of Nature, the scientists programmed harmless strains of bacteria to deliver toxic payloads. When deployed together with a traditional cancer drug, the bacteria shrank aggressive liver tumors in mice much more effectively than either treatment alone.

    The new approach exploits bacteria’s natural tendency to accumulate at disease sites. Certain strains of bacteria thrive in low-oxygen environments such as tumors, and suppression of the host’s immune system also creates favorable conditions for bacteria to flourish.

    “Tumors can be friendly environments for bacteria to grow, and we’re taking advantage of that,” says Sangeeta Bhatia, who is the John and Dorothy Wilson Professor of Health Sciences and Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and its Institute for Medical Engineering and Science.

    Bhatia and Jeff Hasty, a professor of bioengineering at UCSD, are the senior authors of the paper. Lead authors are UCSD graduate student Omar Din and former MIT postdoc Tal Danino, who is now an assistant professor of biomedical engineering at Columbia University.

    Tumor-killing circuits

    The research team began looking into the possibility of harnessing bacteria to fight cancer several years ago. In a study published last year focusing on cancer diagnosis, the researchers engineered a strain of probiotic bacteria (similar to those found in yogurt) to express a genetic circuit that produces a luminescent signal, detectable with a simple urine test, if liver cancer is present.

    These harmless strains of E. coli, which can be either injected or consumed orally, tend to accumulate in the liver because one of the liver’s jobs is to filter bacteria out of the bloodstream.

    In their new study, the researchers delivered artificial genetic circuits into the bacteria, that allow the microbes to kill cancer cells in three different ways. One circuit produces a molecule called hemolysin, which destroys tumor cells by damaging their cell membranes. Another produces a drug that induces the cell to undergo programmed suicide, and the third circuit releases a protein that stimulates the body’s immune system to attack the tumor.

    To prevent potential side effects from these drugs, the researchers added another genetic circuit that allows the cells to detect how many other bacteria are in their environment, through a process known as quorum sensing. When the population reaches a predetermined target level, the bacterial cells self-destruct, releasing their toxic contents all at once. A few of the cells survive to begin the cycle again, which takes about 18 hours, allowing for repeated release of the drugs.

    “That allows us to maintain the burden of the bacteria in the whole organism at a low level and to keep pumping the drugs only into the tumor,” Bhatia says.

    Combination therapy

    The researchers tested the bacteria in mice with a very aggressive form of colon cancer that spreads to the liver. The bacteria accumulated in the liver and began their cycle of growth and drug release. On their own, they reduced tumor growth slightly, but when combined with the chemotherapy drug 5-fluorouracil, often used to treat liver cancer, they achieved a dramatic reduction in tumor size — much more extensive than if the drug was used on its own.

    This approach is well suited to liver tumors because bacteria taken orally have high exposure there, Bhatia says. “If you want to treat tumors outside the gut or liver with this strategy, then you would need to give a higher dose, inject them directly into the tumor, or add additional homing strategies,” she says.

    In previous studies, the researchers found that engineered bacteria that escape from the liver are effectively cleared by the immune system, and that they tend to thrive only in tumor environments, which should help to minimize any potential side effects.

    Martin Fussenegger, a professor of biotechnology and bioengineering at ETH Zurich, calls the new approach “unconventional” and “highly promising.”

    “This is a fascinating, refreshing, and beautiful concept,” says Fussenegger, who was not involved in the study. “In a world of mainstream cancer therapy concepts with often limited success, new therapy strategies are badly needed.”

    The researchers are now working on programming the bacteria to deliver other types of lethal cargo. They also plan to investigate which combinations of bacterial strains and tumor-targeting circuits would be the most effective against different types of tumors.

    The study was funded by the San Diego Center for Systems Biology, the National Institute of General Medical Sciences, the Ludwig Center for Molecular Oncology at MIT, an Amar G. Bose Research Grant, the Howard Hughes Medical Institute, a Koch Institute Support Grant from the National Cancer Institute, and a Core Center Grant from the National Institute of Environmental Health Sciences.

    See the full article here .

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  • richardmitnick 5:59 am on July 23, 2016 Permalink | Reply
    Tags: , Cancer,   

    From CMU: “Algorithm Characterizes How Cancer Genomes Get Scrambled” 

    Carnegie Mellon University logo
    Carnegie Mellon University

    July 21, 2016
    Byron Spice
    412-268-9068
    bspice@cs.cmu.edu

    Research Tool Identifies Interactions Involved in Genetic Changes

    1
    The above artist’s depiction shows extra copies of normally paired chromosomes. Variations in chromosome color show where DNA has become rearranged and duplicated within and between chromosomes. Credit: Ella Marushchenko

    A new method for analyzing the scrambled genomes of cancer cells gives researchers for the first time the ability to simultaneously identify two different types of genetic changes associated with cancers and to identify connections between the two.

    Jian Ma, associate professor in Carnegie Mellon University’s Computational Biology Department, said his new algorithm, called Weaver, could become an important tool for identifying interactions of the alterations within a cancerous cell’s DNA that drive the disease.

    “This work uses a rigorous and elegant approach to give a better picture of the genome changes that occur during the evolution of individual cancers,” said Robert F. Murphy, Ray & Stephanie Lane Professor and Head of the School of Computer Science’s Computational Biology Department. “Having a clearer picture can help identify characteristics, such as responsiveness to drugs, that distinguish cancers and may contribute to developing more personalized treatments.”

    A report on this work by Ma and his former Ph.D. student at the University of Illinois at Urbana-Champaign, Yang Li, was published online today by the journal Cell Systems.

    The genetic code of a healthy cell is embodied by 23 pairs of chromosomes, “but in tumor cells, it’s completely scrambled,” Ma said. Many cancers are known to give rise to multiple copies of chromosomes, a type of mutation known as aneuploidy. Likewise, cancer cells are known to undergo another type of mutation, called structural variations, in which DNA sequences within the chromosomes get rearranged and duplicated.

    Both of these genetic changes can occur within the same cell, but until now separate techniques had to be used to quantify them. Weaver, however, does these analyses simultaneously using the same input — whole genome sequencing data.

    The advantage of doing these analyses simultaneously is that researchers can now see how aneuploidy is affected by structural variations and vice versa. When the analyses are done separately, these interactions are difficult to identify.

    Weaver uses a probabilistic graphical model called Markov Random Field, which enables researchers to visualize not only the number of mutations but also how they connect with each other.

    “This gives us a better view of the complexity of cancer genomes,” Ma said. This may help researchers better characterize cancers or understand which combinations of genetic changes might affect cancer behavior for the same type of cancer or for different cancer types.

    Ma said he anticipates Weaver could provide useful perspective for studies of the Cancer Genome Atlas (TCGA), a collaboration between the National Cancer Institute and the National Human Genome Research Institute that has described the genomes of tumor tissues and matched normal tissues from more than 11,000 patients. The publicly available TCGA dataset includes genomes for 33 different tumor types.

    Ma and Li applied Weaver to whole genome sequencing data for two cancer cell lines and to ovarian cancers from the TCGA. In the case of the ovarian cancer samples, Weaver identified duplicated chromosomal regions caused by a specific type of structural variation, an association not previously reported.

    David C. Schwartz and Shiguo Zhou of the University of Wisconsin-Madison joined Ma and Li in authoring the Cell Systems report. The National Institutes of Health and the National Science Foundation supported this research.

    See the full article here .

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  • richardmitnick 7:20 am on July 15, 2016 Permalink | Reply
    Tags: Cancer, Leukemia - The key to self-destruction,   

    From TUM- Leukemia:”The key to self-destruction” 

    Techniche Universitat Munchen

    Techniche Universitat Munchen

    14.07.2016
    PD Dr. Philipp J. Jost
    III. Medizinische Klinik und Poliklinik
    Klinikum rechts der Isar
    Technical University of Munich
    Tel: +49 (89) 4140-5941
    philipp.jost@tum.de

    1
    In Cancer Cell Ulrike Höckendorf and Dr. Philipp Jost describe a new molecular signaling pathway for self-destruction that is suppressed in leukemia cells. (Foto: Heddergott / TUM)

    When adults develop blood cancer, they are frequently diagnosed with what is referred to as acute myeloid leukemia. The disease is triggered by pathological alterations of bone marrow cells, in which, in addition, an important mechanism is out of action: these cells do not die when they are damaged. Researchers from the Technical University of Munich (TUM) have now discovered a molecular signaling pathway for self-destruction that is suppressed in leukemia cells.

    Leukemia involves pathological alterations in the body’s hematopoietic system. In acute myeloid leukemia, it is specifically the bone marrow (Greek: myelos) that is affected. In a healthy body, different blood cells, which perform different functions in the blood, are formed from stem cells and what is referred to as progenitor cells in the bone marrow. A genetic mutation can lead to alterations in stem cells and progenitor cells and turn them into leukemia-initiating cells, which are referred to as LICs for short. Like healthy progenitor cells, LICs multiply in the bone marrow. The genetic mutation, however, causes LICs to remain without function and prevents them from developing into mature blood cells, which ultimately leads to the repression of healthy hematopoiesis in the bone marrow and the onset of leukemia symptoms.

    The most frequent genetic alterations in myeloid leukemia include mutations in the FLT3 gene. A team led by Dr. Philipp Jost from the Department of Hematology/Oncology at Klinikum rechts der Isar at the Technical University of Munich has now discovered that the effects of this gene on pathologically altered cells in a way provide certain indications for the treatment of the disease. The mutation causes a permanent activation of the FLT3 gene. As demonstrated by the scientists, this triggers inflammation-like stimuli in the cell, subjecting it to permanent stress.

    Growth despite inflammation and damage

    Under normal circumstances, such permanent inflammatory stimuli would trigger a program known as programmed cell death to replace damaged cells. This is a kind of self-destruction mechanism used by a cell to initiate its own destruction in a coordinated fashion and allow it to be replaced by a healthy one. “By contrast, LICs manage to grow and proliferate despite the inflammation and damage,” states Philipp Jost. “In our study, we have taken a closer look at the molecular causes of this resistance.”

    To gain a better understanding of the research project described by the TUM scientists in the medical journal Cancer Cell, it is important to understand that cells have different ways of self-destructing. So far, the primary research focus in trying to ascertain why cancer cells survive longer than they should has been placed on a process called apoptosis. However, the fact that inflammatory processes occur in LICs pointed Philipp Jost and his colleagues in a different direction. Another way to initiate cell death is through what is referred to as necroptosis. Whereas, in apoptosis, a cell shrinks in a coordinated fashion, in necroptosis, a sudden destruction occurs, which releases the contents of the dying cell along with numerous messenger substances. This induces a strong inflammatory stimulus in the vicinity of the cell.

    Cancer cells block activation of protein

    Necroptosis is triggered by the activation of a protein called RIPK3, which subsequently initiates processes within the cell that lead to its death. The scientists used cell cultures to discover that leukemia takes a particularly severe course when RIPK3 is blocked inside LICs. This led to the cancer cells surviving particularly long, accompanied by their strong division and conversion to functionless blood cells (blasts). “We conclude from our findings that particularly aggressive cancer cells have the capacity to block RIPK3,” states Ulrike Höckendorf, lead author of the study. “Exactly how they accomplish this, however, remains to be investigated.”
    Inducing cell death in a LIC by means of necroptosis has repercussions which also affect neighboring leukemia cells. The inflammatory stimuli triggered by the substances released during necroptosis are significantly stronger than the processes caused by the mutation in the FLT3 gene in a LIC. This inflammation has positive effects on the area surrounding the cell: induced by the messenger substances, neighboring leukemia cells begin to mature similar to healthy cells, leading to a less aggressive progression of leukemia.

    With cell death blocked – apoptosis, too, is “neutralized” in many cancer cells – individual LICs manage to survive and proliferate even after chemotherapy or radiotherapy. “The new findings on the impact of the RIPK3 signaling pathway and the messenger substances released could open up new options for the treatment of leukemia,” states Philipp Jost. “If it were possible to artificially reproduce the effect of RIPK3 using medication, one could launch a targeted attack on leukemia cells.”

    Original Publication

    U. Höckendorf, Mo. Yabal, T. Herold, E. Munkhbaatar, S. Rott, S. Jilg, J. Kauschinger, G. Magnani, F. Reisinger, M. Heuser, H. Kreipe, K.Sotlar, T. Engleitner, R. Rad, W. Weichert, C. Peschel, J. Ruland, M. Heikenwalder, K. Spiekermann, J. Slotta-Huspenina, O. Groß, P. Jost. RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells. Cancer Cell Vol. 30:1 (2016). DOI: 10.1016/j.ccell.2016.06.002

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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 6:38 am on July 15, 2016 Permalink | Reply
    Tags: , Cancer, Scientists closer to understanding why red hair genes increase skin cancer risk,   

    From The Guardian: “Scientists closer to understanding why red hair genes increase skin cancer risk” 

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    The Guardian

    12 July 2016
    Nicola Davis

    1
    While redheads might already dodge the sun’s rays, those with only one copy of gene may not realise that they are at risk from the sun’s damaging effects. Photograph: David Leahy/Getty Images

    Scientists are a step closer to understanding why people with the genes for red hair have a greater risk of developing the potentially deadly skin cancer melanoma.

    Research has revealed that patients with the genes for red hair have more mutations in their skin cancer than those without.

    “We have known for a while that there is an association between these [genetic] variants that cause red hair and increased risk of melanoma,” said David Adams, a co-author of the research from the Wellcome Trust Sanger Institute. “What this really does is show at least a contributing factor to that is more mutations.”

    Red hair, fair skin and a sensitivity to the sun are down to variations in a gene called MC1R that affects the production of pigments, called melanins, in the skin.

    “People with red hair have a different type of melanin than people who don’t have red hair – and the type of melanin that redheads have is less able to protect them from the sun,” said Adams.

    About 6% of the UK population have two copies of the MC1R gene variant and hence have red hair, while around 25% of the UK population have only one copy and are typically not redheads. But the new research reveals that patients in both groups show the same number of mutations in their skin cancer.

    The scientists say the findings suggests people with just one copy of the gene might be more susceptible to the damaging effects of sunlight than previously thought.

    Writing in the journal Nature Communications, an international team of researchers describe how they analysed existing genetic data and samples from 405 melanoma patients.

    The scientists found that melanoma patients with redhead gene variants had a greater number of mutations in their skin cancer than those without, with 42% more sun-associated mutations alone.

    But while previous research has shown that the chance of developing melanoma is linked to the number of copies of the redhead gene variants a person has, the new study has thrown up a puzzle.

    “We don’t understand why persons with two MC1R variants are more likely to develop melanoma than those with only one variant, because our [new] data suggest they accumulate mutations at the same rate,” said Tim Bishop, co-author of the study from the University of Leeds.

    The findings, he says, have important implications. While redheads might already dodge the sun’s rays, those with only one copy of gene may not realise that they are at risk from the sun’s damaging effects.

    Adams agrees. “I think there is a general public health message here that there’s a high proportion of the population who need to be careful in the sun,” he said.

    Dr Julie Sharp, head of health and patient information at Cancer Research UK, which co-funded the research, said: “This important research explains why red-haired people have to be so careful about covering up in strong sun. It also underlines that it isn’t just people with red hair who need to protect themselves from too much sun. People who tend to burn rather than tan, or who have fair skin, hair or eyes, or who have freckles or moles are also at higher risk.

    “For all of us the best way to protect skin when the sun is strong is to spend time in the shade between 11am and 3pm, and to cover up with a t-shirt, hat and sunglasses. And sunscreen helps protect the parts you can’t cover; use one with at least SPF15 and four or more stars, put on plenty and reapply regularly.”

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  • richardmitnick 9:39 am on July 14, 2016 Permalink | Reply
    Tags: , Cancer,   

    From Scripps: “Catching Cancer-Causing Mutations in the Act” 

    Scripps
    Scripps Research Institute

    July 2016
    No writer credit found

    Cancer can be caused by mutations in cell DNA, and researchers at The Scripps Research Institute (TSRI) have discovered how one mutation, in a protein known as POT1, causes some of the most aggressive forms of cancer, including leukemia, lymphoma, glioma and melanoma. The research also suggests a possible way to kill these kinds of tumors by targeting an important enzyme.

    1
    Eros Lazzerini Denchi of The Scripps Research Institute co-led the study with Agnel Sfeir of New York University School of Medicine.

    “We’ve found the mechanism through which this mutation leads to a scrambling of the genome,” said TSRI Associate Professor Eros Lazzerini Denchi, who co-led the study with Agnel Sfeir of New York University (NYU) School of Medicine. “That’s when you get really massive tumors.”

    The researchers investigated mutations in a gene that codes for the protein POT1. This protein normally forms a protective cap around the ends of chromosomes (called telomeres), stopping cell machinery from mistakenly damaging the DNA there and causing harmful mutations.

    POT1 is so critical that cells without functional POT1 would rather die than pass on POT1 mutations. Stress in these cells leads to the activation of an enzyme called ATR that triggers programmed cell death.

    Knowing this, scientists in recent years were surprised to find recurrent mutations affecting POT1 in several human cancers, including leukemia and melanoma.

    “Somehow those cells found a way to survive – and thrive,” said Dr. Lazzerini Denchi. “We thought that if we could understand how that happens, maybe we could find a way to kill those cells.”

    Using a mouse model, the researchers found that mutations in POT1 lead to cancer when combined with a mutation in a gene called p53.

    “The cells no longer have the mechanism for dying, and mice develop really aggressive thymic lymphomas,” said Dr. Lazzerini Denchi.

    P53, a well-known tumor suppressor gene, is a cunning accomplice. When mutated, it overrides the protective cell death response initiated by ATR. Then, without POT1 creating a protective cap, the chromosomes are fused together and the DNA is rearranged, driving the accumulation of even more mutations. These mutant cells go on to proliferate and become aggressive tumors. The findings led the team to consider a new strategy for killing these tumors.

    Scientists know that all cells – even cancer cells – will die if they have no ATR. Since tumors with mutant POT1 already have low ATR levels, the researchers think a medicine that knocks out the remaining ATR could kill tumors without affecting healthy cells. “This study shows that by looking at basic biological questions, we can potentially find new ways to treat cancer,” said Dr. Lazzerini Denchi.

    The researchers plan to investigate this new therapeutic approach in future studies.

    See the full article here .

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    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 7:12 am on July 12, 2016 Permalink | Reply
    Tags: , Cancer,   

    From U Cambridge: “Where did it all go wrong? Scientists identify ‘cell of origin’ in skin cancers” 

    U Cambridge bloc

    Cambridge University

    08 Jul 2016
    Craig Brierley
    Craig.Brierley@admin.cam.ac.uk

    1
    Basal cell carcinoma in mouse tail epidermis derived from a single mutant stem cell. Credit: Adriana Sánchez-Danés

    Scientists have identified for the first time the ‘cell of origin’ – in other words, the first cell from which the cancer grows – in basal cell carcinoma, the most common form of skin cancer, and followed the chain of events that lead to the growth of these invasive tumours.

    Our skin is kept healthy by a constant turnover, with dying skin cells being shed and replaced by new cells. The process is maintained by ‘progenitor’ cells – the progeny of stem cells – that divide and ‘differentiate’ into fully-functional skin cells to replenish dying skin. These cells are in turn supported by a smaller population of ‘stem cells’, which remain silent, ready to become active and repair skin when it becomes damaged.

    However, when this process goes awry, cancers can arise: damaged DNA or the activation of particular genes known as ‘oncogenes’ can trigger a cascade of activity that can lead ultimately to unchecked proliferation, the hallmark of a cancer. In some cases, these tumours may be benign, but in others, they can spread throughout the body – or ‘metastasise’ – where they can cause organ failure.

    Until now, there has been intense interest in the scientific field about which types of cell – stem cell, progenitor cell or both – can give rise to tumours, and how those cells become transformed in the process of tumour initiation and growth. Now, in a study published in Nature, researchers led by Professor Cédric Blanpain at the Université Libre de Bruxelles, Belgium, and Professor Ben Simons at the University of Cambridge, have demonstrated in mice how skin stem and progenitor cells respond to the activation of an oncogene. Their studies have shown that, while progenitor cells can give rise to benign lesions, only stem cells have the capacity to develop into deadly invasive tumours.

    The researchers used a transgenic mouse model – a mouse whose genes had been altered to allow the activation of an oncogene in individual stem and progenitor cells. The oncogene was coupled with a fluorescent marker so that cells in which the oncogene was active could be easily identified, and as these cells proliferate, their ‘daughter’ cells could also be tracked. These related, fluorescent cells are known as ‘clones’.

    By analysing the number of fluorescently-labelled cells per clone using mathematical modelling, the team was able to show that only clones derived from mutant stem cells were able to overcome a mechanism known as ‘apoptosis’, or programmed cell death, and continue to divide and proliferate unchecked, developing into a form of skin cancer known as basal cell carcinoma. In contrast, the growth of clones derived from progenitor cells becomes checked by increasing levels of apoptosis, leading to the formation of benign lesions.

    “It’s incredibly rare to identify a cancer cell of origin and until now no one has been able to track what happens on an individual level to these cells as they mutate and proliferate,” says Professor Blanpain. “We now know that stem cells are the culprits: when an oncogene in a stem cell becomes active, it triggers a chain reaction of cell division and proliferation that overcomes the cell’s safety mechanisms.”

    “While this has solved a long-standing scientific argument about which cell types can lead to invasive skin tumours, it is far more than just a piece of esoteric knowledge,” adds Professor Simons from the Cavendish Laboratory at the University of Cambridge. “It suggests to us that targeting the pathways used in regulating cell fate decisions – how stem cells choose between cell proliferation and differentiation – could be a more effective way of halting tumours in their tracks and lead to potential new therapies.”

    The work was supported by the FNRS, TELEVIE, the Fondation Contre le Cancer, the ULB fondation, the foundation Bettencourt Schueller, the foundation Baillet Latour, the European Research Council, Wellcome Trust and Trinity College Cambridge.

    Reference
    Sánchez-Danés, A et al. Defining the clonal dynamics leading to mouse skin tumour initiation. Nature; 8 July 2016; DOI: 10.1038/nature19069

    See the full article here .

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    U Cambridge Campus

    The University of Cambridge[note 1] (abbreviated as Cantab in post-nominal letters[note 2]) is a collegiate public research university in Cambridge, England. Founded in 1209, Cambridge is the second-oldest university in the English-speaking world and the world’s fourth-oldest surviving university.[6] It grew out of an association of scholars who left the University of Oxford after a dispute with townsfolk.[7] The two ancient universities share many common features and are often jointly referred to as “Oxbridge”.

    Cambridge is formed from a variety of institutions which include 31 constituent colleges and over 100 academic departments organised into six schools.[8] The university occupies buildings throughout the town, many of which are of historical importance. The colleges are self-governing institutions founded as integral parts of the university. In the year ended 31 July 2014, the university had a total income of £1.51 billion, of which £371 million was from research grants and contracts. The central university and colleges have a combined endowment of around £4.9 billion, the largest of any university outside the United States.[9] Cambridge is a member of many associations and forms part of the “golden triangle” of leading English universities and Cambridge University Health Partners, an academic health science centre. The university is closely linked with the development of the high-tech business cluster known as “Silicon Fen”.

     
  • richardmitnick 5:19 am on July 12, 2016 Permalink | Reply
    Tags: , Cancer, ,   

    From Science: “Major funders launch international repository of cutting-edge cancer models” 

    AAAS
    Science Magazine

    Jul. 11, 2016
    Jocelyn Kaiser

    1
    An organoid grown from colon cancer cells. Hubrecht Institute

    For decades, cancer biologists have relied on so-called lines of cancer cells for their experiments. But these cultured cells often bear little resemblance to the tumor they came from. That’s because a piece of tumor tissue dropped into a petri dish doesn’t just start growing. Instead, researchers pull out a few cells in the tumor that happen to replicate well—often cells that don’t need the surrounding normal cells that nurture tumors inside the body. And the genetic makeup of cell lines can change over the years they multiply in labs. No wonder, then, that an experimental drug that kills a colon cancer cell line won’t necessarily help a patient with colon cancer.

    Now, several U.S. and European funding agencies want to change that. Today, they’re launching the Human Cancer Models Initiative (HCMI), which aims to give the research community tumor cells that behave more like actual human tumors. The project involves four groups: the U.S. National Cancer Institute (NCI) in Bethesda, Maryland; Cancer Research UK in London; the Wellcome Trust Sanger Institute in Hinxton, U.K.; and the nonprofit Hubrecht Organoid Technology in Utrecht, the Netherlands, which was founded by Hans Clevers, a cancer researcher at the Hubrecht Institute.

    The project will draw on new insights into how to make the mixture of cells from a human tumor grow outside the body. For example, Clevers adds certain growth factors and a gellike matrix to get cells isolated from a particular organ to grow into a similar miniorgan, or organoid. Others use a special bed of mouse cells to coax cells from tumors into growing. When samples of such cells were treated with known cancer drugs, they responded in a way that was remarkably similar to that of mice with tumors grown from these same cells.

    HCMI will scale up production of these tissue-based human cancer models and share them with the community. NCI will fund the development of 600 models; the Sanger Institute and Cancer Research UK will create 200; and the Hubrecht Institute will produce 200 models as part of a 2- to 3-year pilot project. (The total funding level hasn’t yet been determined.) Although the focus will be largely on common cancers, such as colon and pancreatic, NCI will try to include rare and childhood cancers too, says Louis Staudt, director of NCI’s Center for Cancer Genomics.

    Each model will come with a complete genetic analysis and clinical information about the cancer patient it came from, such as whether a specific drug helped them. The project will dovetail with an NCI effort to supplement its 60 workhorse human cancer cell lines with cells derived from patient tissue samples implanted in mice, Staudt says.

    The first samples from the repository could be available to researchers this year. In the long run, says Staudt, he would like to see the project expand to 10,000 models. “I’m extremely excited about this. I think this is big opportunity to boost cancer research. It’s a chance to raise all boats.”

    See the full article here .

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  • richardmitnick 5:21 pm on June 29, 2016 Permalink | Reply
    Tags: , Cancer, , The Cancer Moonshot   

    From LLNL: “Lab’s high performance computing will play major role in Cancer Moonshot initiative” 


    Lawrence Livermore National Laboratory

    Jun. 29, 2016
    Anne M Stark
    stark8@llnl.gov
    925-422-9799

    1
    Lawrence Livermore National Laboratory’s high performance computing capabilities plays a major role in the Cancer Moonshot initiative. Image courtesy of Washington University School of Medicine in St. Louis.

    Vice President Joe Biden and his wife Jill Biden hosted the Cancer Moonshot Summit Wednesday to announce several efforts to expand cancer research in hopes of finding a cure.

    The Cancer Moonshot is a new national effort to double the rate of progress – to make a decade’s worth of advances in cancer prevention, diagnosis, treatment and care in five years – and to ultimately end cancer.

    Lawrence Livermore National Laboratory’s (LLNL) high performance computing plays a major role in the initiative; LLNL Director Bill Goldstein and Jason Paragas of Global Security attended the summit.

    During the summit, the Department of Energy (DOE) launched three new pilot projects focused on bringing together nearly 100 cancer researchers, care providers, computer scientists and engineers to apply the nation’s most advanced supercomputing capabilities to analyze data from preclinical models in cancer, molecular interaction data and cancer surveillance data across four DOE national laboratories. The Collaboration of Oak Ridge, Argonne and Livermore (CORAL) supercomputing, led by Lawrence Livermore, which is typically used for stockpile stewardship, will be applied to biology to refine the understanding of the mechanisms leading to cancer development and accelerating the development of promising therapies that are more effective and less toxic.

    The Biological Applications of Advanced Strategic Computing, or BAASiC, is a multi-institution initiative, led by LLNL. Partners across academia, industry and government share the common vision to enable a revolutionary approach to improve biological understanding, human health and biosecurity through application of advanced computational technology — bringing together large-scale simulation, deep analysis of complex and diverse data and new targeted sensor and measurement technologies.

    DOE and Veterans Affairs are collaborating to apply the most powerful computational assets at the national labs, including Lawrence Livermore, to nearly a half million veterans’ records from one the world largest research cohorts, the Million Veteran Program, a cornerstone of the president’s Precision Medicine Initiative.

    DOE, the National Cancer Institute (NCI) and GlaxoSmithKline also announced a new public-private partnership designed to harness high-performance computing and diverse biological data to accelerate the drug discovery process and bring new cancer therapies from target to first in human trials in under one year.

    Scientists from NCI and national lab researchers from Argonne, Lawrence Livermore, Los Alamos and Oak Ridge, who are part of the Exascale Computing Initiative and the National Strategic Computing Initiative, have been working for nearly two years to produce a plan to use large-scale computing to impact cancer science and, eventually, cancer treatment.

    During the summit, participants were asked to address provocative questions about how the entire cancer system operates and how individuals and organizations can take action to change the status quo to advance progress for patients, with the goal of developing additional actions to be announced through the remainder of 2016 and beyond.

    This was the first time a group this expansive and diverse met under a government charge to double the rate of progress in the understanding, prevention, diagnosis, treatment and care of cancer.

    There were a limited number of speakers and the summit was instead focused on smaller-group interactions, collaborations and networking.

    In January, President Obama signed a Presidential Memorandum establishing a first-of-its-kind federal task force to end cancer as we know it. The Task Force, chaired by Biden, is comprised of leaders from every federal agency that has a part to play in addressing cancer. The administration also announced a new $1 billion initiative to jumpstart The Cancer Moonshot.

    “The Moonshot cannot be achieved by one person, one organization, one discipline or even one collective approach,” Vice President Biden said. “Solving the complexities of cancer will require the formation of new alliances to defy the bounds of innovation and accelerate the prevention, diagnosis, treatment and – ultimately – a cure. It’s going to require millions of Americans speaking up and contributing what they’re able. That’s what the Cancer Moonshot Summit is all about.”

    The attendees at the Cancer Moonshot Summit in Washington, D.C. are leaders representing the entire cancer community and beyond, including researchers, oncologists, nurses and other care providers, data and technology experts, philanthropists, advocates, patients and survivors. They are among the best-positioned individuals and organizations to discuss how cancer affects them, share input for the Cancer Moonshot, generate ideas about how individuals and organizations can better engage in the national effort and create ideas for new collaborations and actions.

    See the full article here .

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    Operated by Lawrence Livermore National Security, LLC, for the Department of Energy’s National Nuclear Security
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