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  • richardmitnick 10:13 am on July 10, 2017 Permalink | Reply
    Tags: , , , Melanoma, Personalized cancer vaccines, Personalized Cancer Vaccines Vanquish Melanoma in Small Study,   

    From SA: “Personalized Cancer Vaccines Vanquish Melanoma in Small Study” 

    Scientific American

    Scientific American

    July 6, 2017
    Sharon Begley

    The therapy trains the immune system to attack tumors.

    1
    Metastatic melanoma cells. Credit: NIH Wikimedia

    A small pilot study raises hopes that personalized cancer vaccines might prove safer and more effective than immune-based therapies already in use or further along in development. In a paper published online in Nature on Wednesday, scientists reported that all six melanoma patients who received an experimental, custom-made vaccine seemed to benefit: their tumors did not return after treatment.

    Researchers not involved in the study praised its results, but with caveats. The scientists “did a beautiful job,” said MD Anderson Cancer Center’s Greg Lizee, an expert in tumor immunology, who called the results “very encouraging.” But because the study did not include a comparison group of patients who received standard treatment and not the vaccine, he cautioned, “it’s not completely proved yet that the lack of [cancer] recurrence was due to the vaccine.”

    See the full article here .

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    Scientific American, the oldest continuously published magazine in the U.S., has been bringing its readers unique insights about developments in science and technology for more than 160 years.

     
  • richardmitnick 10:09 pm on December 25, 2016 Permalink | Reply
    Tags: , , , Melanoma,   

    From Rockefeller: “Researchers develop automated melanoma detector for skin cancer screening” 

    Rockefeller U bloc

    Rockefeller University

    December 23, 2016
    No writer credit

    1
    Malignant or benign?: An image of a skin lesion is processed by a new technology to extract quantitative data, such as irregularities in the shape of pigmented skin, which could help doctors determine if the growth is cancerous.

    Even experts can be fooled by melanoma. People with this type of skin cancer often have mole-looking growths on their skin that tend to be irregular in shape and color, and can be hard to tell apart from benign ones, making the disease difficult to diagnose.

    Now, researchers at The Rockefeller University have developed an automated technology that combines imaging with digital analysis and machine learning to help physicians detect melanoma at its early stages.

    “There is a real need for standardization across the field of dermatology in how melanomas are evaluated,” says James Krueger, D. Martin Carter Professor in Clinical Investigation and head of the Laboratory of Investigative Dermatology. “Detection through screening saves lives but is very challenging visually, and even when a suspicious lesion is extracted and biopsied, it is confirmed to be melanoma in only about 10 percent of cases.”

    In the new approach, images of lesions are processed by a series of computer programs that extract information about the number of colors present in a growth, and other quantitative data. The analysis generates an overall risk score, called a Q-score, which indicates the likelihood that the growth is cancerous.

    Published in Experimental Dermatology, a recent study evaluating the tool’s usefulness indicates that the Q-score yields 98 percent sensitivity, meaning it is very likely to correctly identify early melanomas on the skin. The ability of the test to correctly diagnose normal moles was 36 percent, approaching the levels achieved by expert dermatologists performing visual examinations of suspect moles under the microscope.

    “The success of the Q-score in predicting melanoma is a marked improvement over competing technologies,” says Daniel Gareau, first author of the report and instructor in clinical investigation in the Krueger laboratory.

    The researchers developed this tool by feeding 60 photos of cancerous melanomas and an equivalent batch of pictures of benign growths into image processing programs. They developed imaging biomarkers to precisely quantify visual features of the growths. Using computational methods, they generated a set of quantitative metrics that differed between the two groups of images—essentially identifying what visual aspects of the lesion mattered most in terms of malignancy—and gave each biomarker a malignancy rating.

    By combining the data from each biomarker, they calculated the overall Q-score for each image, a value between zero and one in which a higher number indicates a higher probability of a lesion being a cancerous.

    As previous studies have shown, the number of colors in a lesion turned out to be the most significant biomarker for determining malignancy. And some biomarkers were significant only if looked at in specific color channels—a finding the researchers say could potentially be exploited to identify additional biomarkers and further improve accuracy.

    “I think this technology could help detect the disease earlier, which could save lives, and avoid unnecessary biopsies too,” says Gareau. “Our next steps are to evaluate this method in larger studies, and take a closer look at how we can use specific color wavelengths to reveal aspects of the lesions that may be invisible to the human eye, but could still be useful in diagnosis.”

    This work was supported in part by the National Institutes of Health and in part by the Paul and Irma Milstein Family Foundation and the American Skin Association.

    See the full article here .

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 1:26 pm on December 8, 2015 Permalink | Reply
    Tags: , , Melanoma,   

    From NOVA: “Doctors Finally Decide When a Mole Is Benign and When It’s Cancerous” 

    PBS NOVA

    NOVA

    08 Dec 2015
    Conor Gearin

    1
    A doctor examines a mole on a patient’s back.

    For over 30 years, cancer researchers have argued about moles.

    Specifically, they’ve debated at what point a skin lesion becomes a melanoma, more commonly known as skin cancer.

    2
    A melanoma of approximately 2.5 cm by 1.5 cm

    Some claimed that lesions which looked halfway between a benign mole and a melanoma make up a class of their own, while others held that lesions can only be either harmless or cancerous, with no in-between.

    Over 70,000 new melanomas will be diagnosed in the United States in 2015, according to the American Cancer Society. Recently, a team of researchers led by Hunter Shain of the University of California-San Francisco announced at the Society for Melanoma Research convention that they have new data that settles the debate—a better way of telling whether a lesion is on track for becoming melanoma.

    Intermediate lesions, Shain said, “are very difficult to study simply because they are difficult to identify,” Shain said. Their appearance lies in a gray zone between obviously benign and obviously malignant. When Shain and the team had eight expert dermatologists try to classify them, there was little agreement.

    To get around this problem, the team devised a clever solution, using a characteristic of skin cancer to their advantage. Mature melanomas often lie next to skin tissue that represents earlier stages of the lesion. Taking 37 samples of melanomas from patients, the scientists micro-dissected them into their component sections—healthy skin, precursor lesion, possibly intermediate lesion, and mature melanoma.

    The researchers sequenced nearly 300 cancer-related genes in each section of the samples to discover which genes changed at which stage of development. They found that intermediate lesions had some harmless mutations but also some genetic changes that could lead to cancerous cell growth. That told them those lesions did not just look in between—their DNA actually made their behavior intermediate between a mole and a melanoma.

    The team presented their work at the melanoma convention last week and <a href="http://“>published the full version of the project in the New England Journal of Medicine.

    Sorting out the genetic gray zone also gave them a clearer view of how a melanoma develops. “In our study, we observe the canonical order of mutations that allow a melanocyte [a skin cancer cell] to overcome these barriers as it progresses to melanoma,” Shain said.

    In the 1980s, some researchers described an intermediate lesion as a dysplastic nevus, while others argued that the term would lead to confusions in melanoma diagnosis and shouldn’t be used. Shain’s team avoided using the term dysplastic nevus.

    David Elder of the University of Pennsylvania, who coined the term “dysplastic nevus syndrome” in 1980, attended the team’s presentation in San Francisco. “I think this is an important step forward,” Elder said. “And it does add materially to our understanding of a question that has certainly been hotly debated in our community for many years.”

    While the study’s authors didn’t use his terminology, Elder said they are basically describing the same thing. He said that at the presentation, “I asked the question, ‘Were these intermediate lesions dysplastic nevi or were they something else?’ And the response was, ‘Well, yes, they are.’” Elder agreed that using the term could distract from the study’s main message.

    Iwei Yeh of UC-San Francisco, a co-author of the study and one of the eight expert dermatologists, said that the new genetic data will allow the next stage of research to narrow the list of suspects for which mutations are most likely to lead to melanoma. Researchers could observe people with intermediate lesions and see which ones develop cancer. Then, they could use those genes as diagnostic signals for a mole on track to become malignant.

    “I think that kind of ties into this whole idea of personalized medicine,” Yeh said. “What are the individual alterations that are really contributing to the person’s cancer, and what does that mean for them in terms of their outcome?”

    Elder said this kind of study could reduce unnecessary procedures to remove harmless moles, saving time for both doctors and patients.

    “More precise diagnosis could be very valuable in more appropriate precision treatment of these lesions,” he said. “If you don’t need to do [a procedure], you don’t want to do it.”

    See the full article here .

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

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

    From Weizmann: “Melanoma Mutations Mapped” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    06-07-2015
    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.

    1
    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.

    2
    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.

     
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