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  • richardmitnick 10:27 am on March 22, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From Science 2.0: “Early Kidney Cancer Detection With Urine Test” 

    Science 2.0 bloc

    Science 2.0

    March 22nd 2015
    News Staff

    80 percent of patients survive when kidney cancer is detected early – but it is often not easy. However, finding it early has been among the disease’s greatest challenges.

    Kidney cancer is the seventh most common cancer in men and the 10th most common in women, affecting about 65,000 people each year in the United States. About 14,000 patients die of the disease annually. Like most cancers, kidney tumors are easier to treat when diagnosed early. But symptoms of the disease, such as blood in the urine and abdominal pain, often don’t develop until later, making early diagnosis difficult.

    Now, researchers have developed a noninvasive method to screen for kidney cancer that involves measuring the presence of proteins in the urine. They found that the protein biomarkers were more than 95 percent accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by non-cancerous kidney disease.

    Evan D. Kharasch, M.D., Ph.D., (left) and Jeremiah J. Morrissey, Ph.D. Credit: Elizabethe Holland Durando

    “These biomarkers are very sensitive and specific to kidney cancer,” said senior author Evan D. Kharasch, MD, PhD, of Washington University School of Medicine in St. Louis. “The most common way that we find kidney cancer is as an incidental, fortuitous finding when someone has a CT or MRI scan. It’s not affordable to use such scans as a screening method, so our goal has been to develop a urine test to identify kidney cancer early.”

    When kidney cancer isn’t discovered until after it has spread, more than 80 percent of patients die within five years.

    With researchers from the Siteman Cancer Center, the Mallinckrodt Institute of Radiology and the Division of Urologic Surgery, Kharasch and principal investigator Jeremiah J. Morrissey, PhD, professor of anesthesiology, analyzed urine samples from 720 patients at Barnes-Jewish Hospital who were about to undergo abdominal CT scans for reasons unrelated to a suspicion of kidney cancer. Results of the scans let the investigators determine whether or not patients had kidney cancer. As a comparison, they also analyzed samples from 80 healthy people and 19 patients previously diagnosed with kidney cancer.

    The researchers measured levels of two proteins in the urine — aquaporin-1 (AQP1) and perlipin-2 (PLIN2). None of the healthy people had elevated levels of either protein, but patients with kidney cancer had elevated levels of both proteins.

    In addition, three of the 720 patients who had abdominal CT scans also had elevated levels of both proteins. Two of those patients were diagnosed subsequently with kidney cancer, and the third patient died from other causes before a diagnosis could be made.

    “Each protein, or biomarker, individually pointed to patients who were likely to have kidney cancer, but the two together were more sensitive and specific than either by itself,” said Morrissey. “When we put the two biomarkers together, we correctly identified the patients with kidney cancer and did not have any false positives.”

    Even when patients had other types of non-cancerous kidney disease, levels of the two proteins in the urine were not elevated and did not suggest the presence of cancer.

    “Patients with other kinds of cancer or other kidney diseases don’t have elevations in these biomarkers,” Kharasch said. “So in addition to being able to detect kidney cancer early, another advantage of using these biomarkers may be to show who doesn’t have the disease.”

    Not all kidney masses found by CT scans turn out to be cancerous, he said. In fact, about 15 percent are not malignant.

    “But a CT scan can only tell you whether there is a mass in the kidney, not whether it’s cancer,” Kharasch said. “Currently, the only way to know for sure is to have surgery, and unfortunately, 10 to 15 percent of kidneys removed surgically turn out to be normal.”

    Kharasch and Morrissey are working to develop an easy-to-use screening test for kidney cancer, much like mammograms, colonoscopies or other tests designed to identify cancer at early, more treatable stages before patients have symptoms.

    “By and large, patients don’t know they have kidney cancer until they get symptoms, such a blood in the urine, a lump or pain in the side or the abdomen, swelling in the ankles or extreme fatigue,” Morrissey said. “And by then, it’s often too late for a cure. Metastatic kidney cancer is extremely difficult to treat, and if the disease is discovered after patients have developed symptoms, they almost always have metastases. So we’re hoping to use the findings to quickly get a test developed that will identify patients at a time when their cancer can be more easily treated.”

    Funded by the Barnes-Jewish Hospital Frontier Fund and The Department of Anesthesiology at Washington University School of Medicine in St. Louis, with additional support from the Bear Cub Fund of Washington University, Barnes-Jewish Hospital Foundation and Washington University Institute of Clinical and Translational Science, with additional funding from the National Cancer Institute (NCI) of the National Institutes of Health (NIH). NIH grant numbers R01CA141521 and UL1 TR000448.

    Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Evaluation of urine aquaporin 1 and perilipin 2 concentrations as biomarkers to screen for renal cell carcinoma. JAMA Oncology, published online March 19, 2015.

    See the full article here.

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  • richardmitnick 10:22 am on March 21, 2015 Permalink | Reply
    Tags: , Broad Institute, Cancer,   

    From Broad Institute: “Cancer drug resistance-from laundry list to paradigms” 

    Broad Institute

    Broad Institute

    March 20th, 2015
    Lisa Girard

    Image by Broad Communications

    Drug resistance is one of the greatest obstacles to effective cancer therapy. Research has shown that cancer cells can use any number of genes and strategies to achieve or acquire resistance to particular therapies. Until recently, scientists have taken a piecemeal approach to understanding the problem of resistance—unraveling individual mechanisms without reaching any kind of overarching theme.

    “In terms of resistance to targeted therapy there are a lot of publications—a laundry list of mechanisms. It can make you bleary-eyed,” says Broad Institute member Levi Garraway. “We know a gazillion ways to develop resistance, but how does that knowledge help us develop better therapeutic regimens?”

    Garraway and his colleagues suspect that individual resistance mechanisms often coalesce into common cellular downstream effects. For example, half of all melanoma cancers have a mutation in a signaling factor called BRAF. BRAF then signals to another factor, MEK, which signals to another factor called ERK, which then triggers cell growth. The current treatment for this type of cancer uses a combination of BRAF and MEK inhibitors to shut the pathway down. There are several different resistance mechanisms, but many have the same effect: they are able to switch on ERK.

    In the broadest sense, resistance mechanisms could be put into three main categories 1) a pathway gets turned back on; 2) a pathway is bypassed; or 3) a cell enters an alternative cell state in which the pathway is no longer relevant.

    “We actually don’t think it’s a laundry list of mechanisms,” says Garraway. “We think that by mapping out the landscape of resistance we will be able to learn that while there might be 50, 60, 70, or more individual genes that can cause resistance, they actually converge onto a smaller number of common cellular effects.” The aim is to understand the networks in a cell that are critical for the drug resistant state, and identify targets where many signals converge.

    In the hope of understanding the functional landscape of resistance, Broad researcher and first author Rick Wilson, Garraway, and colleagues looked at the ability of over 12,000 genes to confer resistance to inhibitors of oncogenic ALK in ALK-dependent lung cancer. Their goal was to identify functional categories of resistance genes, as well as identify new genes.

    Results of the study, recently published in Cancer Cell, identify a number of genes known to play a role in other types of drug-resistant cancer, including kinases, adaptor molecules, and transcription factors, but as the researchers suspected, they also point to a previously undetected pathway parallel to the MAPK pathway that starts with a family of G protein coupled receptors called purinergic receptors. The resistance mechanism linked to those receptors appeared, at least in part, to go through a signaling molecule called Protein Kinase C (PKC). Similar to the effect of ERK in melanoma, switching on PKC alone triggered significant resistance in cellular models.

    While many current therapies target upstream pathway components, this study demonstrates the potential usefulness of therapeutically targeting factors closer to the transcriptional output.

    “By targeting critical downstream components, potential upstream resistance mechanisms may no longer be sufficient to drive resistance,” says Wilson. Wilson believes that detailed characterization of patient tumors may provide insight in terms of prioritizing some pathways over others.

    How can these findings ultimately translate into better cancer therapy regimens? In the past, scientists sought to understand resistance mechanisms so that if a tumor did become resistant, it would be possible to make it sensitive again. Now the goals have shifted to account for the heterogeneous and multifactorial nature of tumors, and understanding resistance is critical so that patients can receive combination therapies up front to avoid or delay resistance in the first place.

    “With a global understanding we can start to piece together the networks that matter for achieving resistance to oncogene-directed therapy,” says Garraway. “Eventually, this understanding will help us develop new therapeutic combinations to overcome these mechanisms.”

    Other scientists contributing to this work include Cory M. Johannessen, Federica Piccioni, Pablo Tamayo, Jong Wook Kim, Eliezer M. Van Allen, Steven M. Corsello, Marzia Capelletti, Antonio Calles, Mohit Butaney, Tanaz Sharifnia, Stacey B. Gabriel, Jill P. Mesirov, William C. Hahn, Jeffrey A. Engelman, Matthew Meyerson, David E. Root, and Pasi A. Jänne.

    Wilson F, et al. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer. Cancer Cell. 27, 397-408 (9 March 2015). DOI: http://dx.doi.org/10.1016/j.ccell.2015.02.005

    See the full article here.

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    The Eli and Edythe L. Broad Institute of Harvard and MIT is founded on two core beliefs:

    This generation has a historic opportunity and responsibility to transform medicine by using systematic approaches in the biological sciences to dramatically accelerate the understanding and treatment of disease.
    To fulfill this mission, we need new kinds of research institutions, with a deeply collaborative spirit across disciplines and organizations, and having the capacity to tackle ambitious challenges.

    The Broad Institute is essentially an “experiment” in a new way of doing science, empowering this generation of researchers to:

    Act nimbly. Encouraging creativity often means moving quickly, and taking risks on new approaches and structures that often defy conventional wisdom.
    Work boldly. Meeting the biomedical challenges of this generation requires the capacity to mount projects at any scale — from a single individual to teams of hundreds of scientists.
    Share openly. Seizing scientific opportunities requires creating methods, tools and massive data sets — and making them available to the entire scientific community to rapidly accelerate biomedical advancement.
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  • richardmitnick 1:42 pm on March 20, 2015 Permalink | Reply
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    From Scripps: ” Scientists Confirm Key Targets of New Anti-Cancer Drug Candidates” 


    Scripps Research Institute

    March 23, 2015
    Eric Sauter

    Ribosomes, ancient molecular machines that produce proteins in cells, are required for cell growth in all organisms, accomplishing strikingly complex tasks with apparent ease. But defects in the assembly process and its regulation can lead to serious biological problems, including cancer.

    Now, in a study published in the March 16 issue of The Journal of Cell Biology, scientists from the Florida campus of The Scripps Research Institute (TSRI) have confirmed the ribosome assembly process as a potentially fertile new target for anti-cancer drugs by detailing the essential function of a key component in the assembly process.

    “This study confirms that ribosome assembly is a good therapeutic target in cancer,” said Katrin Karbstein, a TSRI associate professor who led the study. “Whether or not we have pinpointed the best molecule remains to be shown, but this is a vindication of our basic research. There should be effort devoted to exploring this pathway.”

    Understanding ribosome assembly—which involves about 200 essential proteins known as “assembly factors” in addition to the four RNA molecules and 78 ribosomal proteins that are part of the mature ribosome—has become a fruitful area of research in recent years because of the importance of ribosome assembly for cell growth.

    The new study highlights the molecules Casein kinase 1δ (CK1δ) and CK1ε, which are essential for human ribosome assembly. The expression of CK1δ is elevated in several tumor types, as well as Alzheimer’s and Parkinson’s disease—and CK1δ inhibitors have shown promise in some pre-clinical animal studies.

    In the new study, Karbstein and her group—working closely with three labs across the state of Florida, including the laboratory of William Roush at Scripps Florida—used Hrr25, the yeast equivalent of Casein kinase 1δ (CK1δ) and CK1ε, as a research model.

    In biochemical experiments, the team showed that Hrr25 is necessary for ribosome assembly and that the molecule normally adds a phosphate group to an assembly factor called “Ltv1,” allowing it to separate from other subunits and mature. If Hrr25 is inactivated or a mutation blocks the release of Ltv1, the assembly process is doomed.

    “Inhibiting Hrr25 and the subsequent release of Ltv1 blocks the formation of other subunits that are required for maturation—and the subsequent production of proteins,” said Homa Ghalei, the first author of the study and a member of the Karbstein lab.

    In additional experiments on human breast cancer cells, the researchers showed that CK1δ/CK1ε inhibitors no longer induce programmed cell death (“apoptosis”) and prevent cancer cells from growing when Ltv1 is removed.

    “This clearly establishes that the anti-proliferative potency of these inhibitors is in large part due to blocking ribosome assembly,” Karbstein said.

    In addition to Karbstein and Ghalei, other authors of the study, Hrr25/CK1d-Directed Release of Ltv1 From Pre-40S Ribosomes Is Necessary For Ribosome Assembly And Cell Growth (10.1083/jcb.201409056), are Joanne R. Doherty, Yoshihiko Noguchi and William R. Roush of TSRI; Franz X. Schaub and John L. Cleveland of The Moffitt Cancer and Research Institute; and M. Elizabeth Stroupe of Florida State University. See http://jcb.rupress.org/content/208/6/745.abstract

    The work was supported by the National Institutes of Health (grants R01-GM086451, CA154739, U54MH074404 and P30-CA076292), the National Science Foundation (grant 1149763), the ThinkPink Kids Foundation, the PGA National Women’s Cancer Awareness Days and the Swiss National Foundation (P300P3-147907).

    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 11:19 am on March 15, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From Science 2.0: “Fractal Patterns May Uncover New Line Of Attack On Cancer” 

    Science 2.0 bloc

    Science 2.0

    March 15th 2015
    News Staff

    The appearance of fractal patterns on the surface of cancer cells. Credit: Credit: M. Dokukin and I. Sokolov

    Studying the intricate fractal patterns on the surface of cells could give researchers a new insight into the physical nature of cancer, and provide new ways of preventing the disease from developing.

    This is according to scientists in the US who have, for the first time, shown how physical fractal patterns emerge on the surface of human cancer cells at a specific point of progression towards cancer.

    Publishing their results today, 11 March, in the Institute of Physics and Germany Physical Society’s New Journal of Physics, they found that the distinctive repeating fractal patterns develop at the precise point in which precancerous cells transform into cancer cells, and that fractal patterns are not present either before or after this point.

    The researchers hope the new findings can inspire biologists to search for specific “weak” points in the pathways that lead to the alteration of precancerous cells at this specific moment. By targeting these weak points, the researchers believe they could influence the process and thus prevent cancer from developing.

    Lead author of the study Professor Igor Sokolov said: “Despite many decades of fighting cancer, the war is far from being victorious. A sharp increase in the complexity and variability of genetic signatures has slowed the advancement based on finding specific cancer genes in patients.

    “Thus, more than ever, there is a need for new conceptual paradigms about the nature of cancer, and what we have found adds towards the development of such paradigm.”

    The term “fractal” defines a pattern that, when you take a small part of it, looks similar, although perhaps not identical, to its full structure. For example, the leaf of a fern tree resembles the full plant and a river’s tributary resembles the shape of the river itself.

    Nature is full of fractal patterns; they can be seen in clouds, lightning bolts, crystals, snowflakes, mountains, and blood vessels. Fractal patterns develop in conditions that are far-from-equilibrium, or chaotic–systems that are not in a state of rest or balance.

    In their study, the researchers, consisting of Dr Dokukin and Prof Sokolov from Tufts University and Ms Guz and Prof Woodworth from Clarkson University, used atomic force microscopy to produce extremely high-resolution images of the surfaces of human cervical epithelial cells.

    The cells were studied in vitro as they progressed from normal cells to immortal (premalignant) cells to malignant cells.

    “Despite previous expectations that fractal patterns are associated with cancer cells, we found that fractal geometry only occurs at a limited period of development when immortal cells become cancerous,” Professor Sokolov continued.

    “We also found that cells deviate more from fractal when they further progress towards cancer, and confirmed that normal cells do not have fractal patterns.”

    Whilst it is still unclear if the presence of fractal patterns plays any part in the development or progression of cancer itself, the researchers state that it is definitely plausible to expect that they have some importance given the role that the cell surface plays in metastasis.

    Professor Sokolov said: “When cancer metastasizes and spreads through the body, cancer cells have to physically crawl through multiple tissues, overcoming friction and resistance through interactions on the cells surface.

    “Moving forward, we need to further our understanding as to how important the cell surface is in the development of cancer.”

    See the full article here.

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  • richardmitnick 8:05 am on March 13, 2015 Permalink | Reply
    Tags: , , Cancer   

    From AAAS: “Why a powerful cancer drug only helps some patients” 



    12 March 2015
    Jocelyn Kaiser

    T cells attacking a tumor cell. (Steve Gschmeissner/Science Source)

    A new type of drug that unleashes the immune system on tumors has been a remarkable success, but only for some cancer patients. Now researchers have found a genetic signature within lung tumors that seems to predict whether this immunotherapy drug will work—and who will benefit most.

    Tumor cells can hide from the immune system by activating a receptor, called PD-1, on the surface of the immune cells known as T cells. Instead of attacking the tumor cells, the T cells leave them alone. The new drug is an antibody that inhibits PD-1, blocking this “checkpoint” and freeing the T cells to wipe out the tumor cells. In clinical trials, PD-1 blockers and other checkpoint inhibitors have extended the lives of patients with several cancer types for years, far longer than conventional treatments. The U.S. Food and Drug Administration has approved several of these drugs for melanoma and one of them, nivolumab, became the first to win approval for lung cancer last week. But checkpoint inhibitors work only for some people—PD-1 inhibitors shrink tumors in about 20% to 30% of lung cancer patients—and researchers are scrambling to figure out why.

    One hypothesis is that checkpoint inhibitors are more likely to work on tumors that have more mutations. These mutations are not necessarily those that allow tumor cells to divide uncontrollably or spread to other places; instead, they may simply encode abnormal proteins that do nothing for the cancer cell. But they can matter for immunotherapies because the aberrant molecules may act as antigens—foreign molecules in the body that trigger an immune response. The more mutations in a patient’s tumor, the more of these so-called neoantigens, and hence a stronger response from T cells in patients taking a checkpoint inhibitor, the thinking goes.

    Some recent studies support this view. Melanoma patients with more neoantigen-coding mutations in their tumors, for example, were more likely to respond to a checkpoint inhibitor that blocks a protein called CTLA-4.

    Now, the same seems to hold true for lung cancer. Timothy Chan of Memorial Sloan Kettering Cancer Center in New York City, who led the melanoma study, and co-workers sequenced the exome—the protein-coding DNA—of tumors from 34 people with non-small cell lung cancer who had been treated with a PD-1 inhibitor called pembrolizumab. They found that patients were much more likely to respond to the drug if their tumor had more of the type of mutation that results in an altered protein. For example, 13 of 18 (72%) patients with at least 178 mutations responded for 6 months or longer, compared with one of 13 (8%) of those with fewer mutations. Moreover, the 16 lung cancer patients who had a distinctive pattern of mutations caused by smoking were more likely to respond than the presumed nonsmokers, who had fewer, different mutations, Chan’s group reports online today in Science.

    The correlation between mutations and therapeutic response to the cancer drugs is “eye-popping,” says cancer researcher Drew Pardoll of Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved with the study but has collaborated with Chan’s group. “It’s a very important result.” Although the results don’t necessarily mean that all nonsmokers won’t respond to PD-1 blockers, sequencing the DNA of tumor biopsies could help oncologists decide which drug to give first, he and Chan say. And it suggests these drugs may work on other smoking-related cancers, such as esophageal and head and neck cancers, Chan adds.

    Researchers are also exploring the possibility of giving patients a personalized vaccine made from the neoantigens in their tumor to bolster their response to a checkpoint inhibitor. “I think the potential here is enormous,” says Roy Herbst, a lung cancer researcher at Yale University.

    See the full article here.

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  • richardmitnick 4:04 am on March 11, 2015 Permalink | Reply
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    From Medicalxpress: “Researchers identify control mechanism for glutamine uptake in breast cancer cells” 

    Medicalxpress bloc


    March 10, 2015
    No Writer Credit

    Electron microscopic image of a single human lymphocyte. Credit: Dr. Triche National Cancer Institute

    Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have discovered a mechanism that explains why some breast cancer tumors respond to specific chemotherapies and others do not. The findings highlight the level of glutamine, an essential nutrient for cancer development, as a determinant of breast cancer response to select anticancer therapies, and identify a marker associated with glutamine uptake, for potential prognosis and stratification of breast cancer therapy.

    “Our study indicates that a protein called RNF5 determines breast cancer response to paclitaxel, one of the most common chemotherapy drugs,” said Ze’ev Ronai, Ph.D., scientific director of Sanford-Burnham’s La Jolla campus. “Paclitaxel belongs to a class of drugs called taxanes that work by triggering a stress response in cells that in turn promotes an interaction between RNF5 and glutamine uptake proteins. We found that this interaction causes degradation of the glutamine carrier proteins, leading to an insufficient supply of glutamine and the sensitization of breast cancer tumors to death.”

    The study results were published in today’s online edition of Cancer Cell.

    For some time researchers have known that many tumor cell types are dependent on glutamine for growth and survival, but didn’t know how glutamine uptake was regulated. The new findings demonstrate the importance of RNF5 in the control of glutamine uptake, and in antagonizing tumor development. The findings also suggest that testing tumors for RNF5 and glutamine carrier protein levels, such as SLC1A5, may be used to identify patients best suited to taxanes-based therapy.

    “Not all tumors are equipped to respond to paclitaxel therapy,” said Ronai. “Using a cohort of more than 500 breast cancer patient samples, we found that only 30 percent of tumors exhibit high levels of RNF5 and low levels of glutamine carrier proteins—the optimal profile for response to paclitaxel.”

    “Understanding these types of cell mechanisms and tumor characteristics that determine the response to anticancer drugs can lead to better patient stratification as well as improved therapy approaches,” said Gordon Mills, M.D., Ph.D., chairman of the Department of Systems Biology at MD Anderson Cancer Center, 2013 recipient of the Susan B. Komen Brinker Award for contributions to breast cancer research, and co-author of the study. “The opportunity to identify and target key pathways involved in the behavior of breast cancer cells has the potential to both increase efficacy and decrease toxicity of therapy.”

    “We also used this patient cohort to test the predictive value of measuring levels of glutamine carrier proteins as a prognostic marker,” said Ronai. Our results indicate that these proteins are an outstanding marker of patient outcome, as good as currently used markers.”

    “We have started screening for inhibitors of glutamine carrier proteins as a potential new target for breast cancer treatment,” said Ronai, who is also examining the mechanism for glutamine control in other tumor types.

    See the full article here.

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

  • richardmitnick 9:45 am on February 19, 2015 Permalink | Reply
    Tags: , Cancer,   

    From U Washington: “Tumor genetics traces cancer cells’ origins” 

    U Washington

    University of Washington

    Brigham and Women’s Hospital
    Haley Bridger
    617-525-6383, hbridger@partners.org

    University of Washington
    Leila Gray
    206-685-0381, leilag@uw.edu

    An artists conception of the chromatin packing of DNA (Mary Jo Chmielewski/CellsSixthGrade)

    New possibilities for tracing cancer of unknown origin back to the type of cell in which it began are reported today.

    The approach benefits from the wealth of information being gleaned from epigenomes. The epigenome consists of all the chemical packaging and tags attached to genes in an individual’s complete DNA sequence. While these compounds may regulate gene activity, they do not alter the DNA code.

    By leveraging the epigenome maps produced by the Roadmap Epigenomics Program – a resource of data collected from over 100 cell types – a multi-instutional research team found that the unique genetic landscape of a particular tumor could be used to predict that tumor’s cell type of origin.

    The study provides new insights into the early events that shape a cancer. It also could have important implications for the many patients for whom the originating site of their cancer is unknown.

    The paper, Cell-of-origin chromatin organization shapes the mutational landscape of cancer, is one of several published today in Nature as part of collection reporting the latest advances epigenomics.

    “When people planned the Roadmap Epigenomics Project as a resource focusing on normal cells and tissues, nobody thought about cancer mutations and predicting a cancer’s cell of origin – this wasn’t on anyone’s radar,” said co-senior author Shamil Sunyaev, a research geneticist at Boston’s Brigham and Women’s Hospital, a teaching affiliate of Harvard Medical School. “Our study suggests that we can now predict, specifically for different cancer types, where mutations will happen in a given cancer and what was that cancer’s likely cell of origin based on genomic sequence.”

    Mutations are the driving force behind cancer, but they are not distributed evenly across a cancer cell’s genome. The researchers, made up of a team from the Broad Institute of MIT and Harvard and the University of Washington in Seattle, hypothesized that this variation in the “mutational landscape” might be influenced by chromatin structure, or the way that DNA is packaged, which varies widely from cell type to cell type.

    The National Institutes of Health Common Fund’s Roadmap Epigenomics Program, which set out to chart chromatin features from a variety of tissue types and cell types, gave the researchers a means to test this hypothesis. They looked to see how the genomic sequence of cancer cells corresponded with the chromatin structure of different normal cell types, which is highly characteristic for each cell type. The research team investigated samples from a diverse range of cancer types including myeloma, colon cancer, brain cancer and more. What they found was unexpected: the variation in the cancer mutational landscape was very strongly tied to chromatin structure, and because the chromatin structure patterns of cells are so unique, they could use a cancer’s mutation patterns to predict the likely cell type from which it originated.

    About 2% to 5% percent of cancer patients have a cancer whose primary site remains unknown. Cancer of unknown primary origin can pose challenges for treatment decisions, which are often influenced or based on the origin site of cancer.

    “This work could have implications for treatment – frequently, we’re confronted in the clinic with individuals that present with metastatic cancer from an unknown primary site, which makes it very difficult to choose the right initial treatment regimen,” said co-senior author John Stamatoyannopoulos, UW associate professor of genome sciences and medicine, Division of Oncology. “Our finding that the pattern of mutations in the cancer’s genomic sequence is such a strong predictor of its originating cell type thus might help guide such treatment decisions, and could be increasingly feasible as cancer genome sequencing becomes more routine.”

    Combining epigenomic resources and cancer genomic information may also give researchers insights into an early time period in cancer’s development for which little information is currently available. Understanding how chromatin structure shapes the landscape of mutations in a cancer cell could inform researchers’ understanding of the events that first give rise to cancer, as well as how cancers evolve over time.

    “This provides a window into these early, unseen events we never had access to before,” said Sunyaev, who is also an associate member of the Broad Institute and professor at Harvard Medical School. “We can now take advantage of the data that was hidden in these mutational patterns – we don’t fully know how to mine all of that data yet, but it’s likely to hold even more information than what we’ve figured out already.”

    This work was supported by NIH R01 MH101244, U54, CA143874, U01 ES017156, P01 HL53750, U54 HG007010, the Integra-Life Seventh Framework Program (grant number
    315997) and the EMBO Young Investigator Program (Installation grant 1431/2006).

    See the full article here.

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us — the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

  • richardmitnick 5:34 am on February 13, 2015 Permalink | Reply
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    From phys.org: “Gold nanotubes launch a three-pronged attack on cancer cells” 


    Feb 13, 2015

    Pulsed near infrared light (shown in red) is shone onto a tumour (shown in white) that is encased in blood vessels. The tumour is imaged by multispectral optoacoustic tomography via the ultrasound emission (shown in blue) from the gold nanotubes. Credit: Jing Claussen (Ithera Medical, Germany)

    Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells.

    The study, published today in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer.

    Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said: “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects.

    Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

    The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

    The study’s corresponding author Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds, said: “Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it.

    “When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

    In cell-based studies, by adjusting the brightness of the laser pulse, the researchers say they were able to control whether the gold nanotubes were in cancer-destruction mode, or ready to image tumours.

    In order to see the gold nanotubes in the body, the researchers used a new type of imaging technique called ‘multispectral optoacoustic tomography’ (MSOT) to detect the gold nanotubes in mice, in which gold nanotubes had been injected intravenously. It is the first biomedical application of gold nanotubes within a living organism. It was also shown that gold nanotubes were excreted from the body and therefore are unlikely to cause problems in terms of toxicity, an important consideration when developing nanoparticles for clinical use.

    Study co-author Dr James McLaughlan, from the School of Electronic & Electrical Engineering at the University of Leeds, said: “This is the first demonstration of the production, and use for imaging and cancer therapy, of gold nanotubes that strongly absorb light within the ‘optical window’ of biological tissue.

    “The nanotubes can be tumour-targeted and have a central ‘hollow’ core that can be loaded with a therapeutic payload. This combination of targeting and localised release of a therapeutic agent could, in this age of personalised medicine, be used to identify and treat cancer with minimal toxicity to patients.”

    The use of gold nanotubes in imaging and other biomedical applications is currently progressing through trial stages towards early clinical studies.

    See the full article here.

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    Phys.org™ (formerly Physorg.com) is a leading web-based science, research and technology news service which covers a full range of topics. These include physics, earth science, medicine, nanotechnology, electronics, space, biology, chemistry, computer sciences, engineering, mathematics and other sciences and technologies. Launched in 2004, Phys.org’s readership has grown steadily to include 1.75 million scientists, researchers, and engineers every month. Phys.org publishes approximately 100 quality articles every day, offering some of the most comprehensive coverage of sci-tech developments world-wide. Quancast 2009 includes Phys.org in its list of the Global Top 2,000 Websites. Phys.org community members enjoy access to many personalized features such as social networking, a personal home page set-up, RSS/XML feeds, article comments and ranking, the ability to save favorite articles, a daily newsletter, and other options.

  • richardmitnick 5:49 am on February 12, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From Rutgers: “Ingredient in Olive Oil Looks Promising in the Fight Against Cancer” 

    Rutgers University
    Rutgers University

    February 12, 2015
    Ken Branson

    Extra-virgin olive oil contains an ingredient, oleocanthal, that kills cancer cells without harming healthy cells, researchers have found.

    A Rutgers nutritional scientist and two cancer biologists at New York City’s Hunter College have found that an ingredient in extra-virgin olive oil kills a variety of human cancer cells without harming healthy cells.

    The ingredient is oleocanthal, a compound that ruptures a part of the cancerous cell, releasing enzymes that cause cell death.

    Paul Breslin, professor of nutritional sciences in the School of Environmental and Biological Sciences, and David Foster and Onica LeGendre of Hunter College, report that oleocanthal kills cancerous cells in the laboratory by rupturing vesicles that store the cell’s waste. LeGendre, the first author, Foster, the senior author, and Breslin have published their findings in Molecular and Cellular Oncology.

    According to the World Health Organization’s World Cancer Report 2014, there were more than 14 million new cases of cancer in 2012 and more than 8 million deaths.

    Scientists knew that oleocanthal killed some cancer cells, but no one really understood how this occurred. Breslin believed that oleocanthal might be targeting a key protein in cancer cells that triggers a programmed cell death, known as apoptosis, and worked with Foster and Legendre to test his hypothesis after meeting David Foster at a seminar he gave at Rutgers.

    “We needed to determine if oleocanthal was targeting that protein and causing the cells to die,” Breslin said.

    After applying oleocanthal to the cancer cells, Foster and LeGendre discovered that the cancer cells were dying very quickly – within 30 minutes to an hour. Since programmed cell death takes between 16 and 24 hours, the scientists realized that something else had to be causing the cancer cells to break down and die.

    LeGendre, a chemist, provided the answer: The cancer cells were being killed by their own enzymes. The oleocanthal was puncturing the vesicles inside the cancer cells that store the cell’s waste – the cell’s “dumpster,” as Breslin called it, or “recycling center,” as Foster refers to it. These vesicles, known as lysosomes are larger in cancer cells than in healthy cells, and they contain a lot of waste. “Once you open one of those things, all hell breaks loose,” Breslin said.

    But oleocanthal didn’t harm healthy cells, the researchers found. It merely stopped their life cycles temporarily – “put them to sleep,” Breslin said. After a day, the healthy cells resumed their cycles.

    The researchers say the logical next step is to go beyond laboratory conditions and show that oleocanthal can kill cancer cells and shrink tumors in living animals. “We also need to understand why it is that cancerous cells are more sensitive to oleocanthal than non-cancerous cells,” Foster said.

    See the full article here.

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

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

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  • richardmitnick 3:10 pm on February 5, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From NOVA: “Electric Fields Carrying Chemo Could Destroy Intractable Tumors” 



    05 Feb 2015
    Tim De Chant

    There’s no “good” cancer, but some are certainly worse than others when it comes to prognosis. Pancreatic cancer, for example, has a dismal survival rate. It’s inoperable in many cases, and in general it’s hard to deliver chemo to the tumor because its internal pressure keeps drugs at bay.

    Researchers have been devising strategies to concentrate chemo in the most recalcitrant tumors, from injecting drugs directly into tumors themselves to directing chemo-coated magnetic particles to the site. The latest takes some of these ideas a step further while using existing drugs, a time-saving step. It comes in the form of a device that stores chemo and produces electric fields that carry the drugs directly into the tumor. Because many existing drugs are polar molecules, they are carried along with the electric current.

    Pancreatic cancer cells, seen here through a powerful microscope, are targeted by the new treatment.

    Inventors Joseph DeSimone, a professor of chemistry at the University of North Carolina, Chapel Hill, and his team have tested their device on mice and dogs, and the approach shows promise. Here’s Robert F. Service, reporting for Science:

    The team got several promising results. In one experiment, the researchers started with mice that had been implanted with human pancreatic cancer tumors. One group of mice was then implanted with the electrode setup and administered an anticancer drug called gemcitabine twice a week for 7 weeks. Control animals received either saline through the same electrode setup or intravenous (IV) doses of saline or gemcitabine. The researchers report online today in Science Translational Medicine that the animals in the experimental group had far higher gemcitabine concentrations in their tumors compared with mice that received the IV drug. That caused the tumors to shrink dramatically in the experimental animals, whereas tumors in mice that received IV gemcitabine or saline continued to grow.

    Another advantage of the approach is that it limits the distribution of chemo within the body. Though the drugs are highly toxic to cancer cells, they also are taxing to healthy cells, making treatment regimens grueling affairs.

    DeSimone and his team have yet to move the device into clinical trials involving humans, an often unsuccessful transition for many would-be cancer treatments. Still, the fact that the device relies on delivering known, existing drugs more directly to a tumor site should reduce some uncertainty.

    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.

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