Tagged: Cancer Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 9:31 am on July 28, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From CERN: “A miniature accelerator to treat cancer” 

    CERN New Masthead

    28 Jul 2015
    Matilda Heron

    Serge Mathot with the first of the four modules that will make up the miniature accelerator (Image: Maximilien Brice/CERN)

    CERN, home of the 27-kilometre Large Hadron Collider (LHC), is developing a new particle accelerator. just two metres long.

    The miniature linear accelerator (mini-Linac) is designed for use in hospitals for imaging and the treatment of cancer. It will consist of four modules, each 50cm long, the first of which has already been constructed. “With this first module we have validated all of the stages of construction and the concept in general”, says Serge Mathot of the CERN engineering department.

    Designing an accelerator for medical purposes presented a new technological challenge for the CERN team. “We knew the technology was within our reach after all those years we had spent developing Linac4,” says Maurizio Vretenar, coordinator of the mini-Linac project. Linac4, a larger accelerator designed to boost negative hydrogen ions to high energies, is scheduled to be connected to the CERN accelerator complex in 2020.

    The miniature accelerator is a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains. RFQs are designed to produce high-intensity beams. The challenge for the mini-Linac was to double the operating frequency of the RFQ in order to shorten its length. This desired high frequency had never before been achieved. “Thanks to new beam dynamics and innovative ideas for the radiofrequency and mechanical aspects, we came up with an accelerator design that was much better adapted to the practical requirements of medical applications,” says Alessandra Lombardi, in charge of the design of the RFQ.

    The “mini-RFQ” can produce low-intensity beams, with no significant losses, of just a few microamps that are grouped at a frequency of 750 MHz. These specifications make the “mini-RFQ” a perfect injector for the new generation of high-frequency, compact linear accelerators used for the treatment of cancer with protons.

    And the potential applications go beyond hadron therapy. The accelerator’s small size and light weight mean that is can be set up in hospitals to produce radioactive isotopes for medical imaging. Producing isotopes on site solves the complicated issue of transporting radioactive materials and means that a wider range of isotopes can be produced.

    The “mini-RFQ” will also be capable of accelerating alpha particles for advanced radiotherapy. As the accelerator can be fairly easily transported, it could also be used for other purposes, such as the analysis of archaeological materials.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Meet CERN in a variety of places:

    Cern Courier



    CERN CMS New

    CERN LHCb New


    CERN LHC New
    CERN LHC Grand Tunnel

    LHC particles

    Quantum Diaries

  • richardmitnick 8:24 am on July 23, 2015 Permalink | Reply
    Tags: , , Cancer, MAGI   

    From Brown: “Web app helps researchers explore cancer genetics” 

    Brown University
    Brown University

    This post is dedicated to Eli Mitnick to honor his work in Cancer research

    July 23, 2015
    Kevin Stacey 401-863-3766


    Brown University computer scientists have developed a new interactive tool to help researchers and clinicians explore the genetic underpinnings of cancer.

    The tool — dubbed MAGI, for Mutation Annotation and Genome Interpretation — is an open-source web application that enables users to search, visualize, and annotate large public cancer genetics datasets, including data from The Cancer Genome Atlas (TCGA) project.

    “The main motivation for MAGI has been to reduce the computational burden required for researchers or doctors to explore and annotate cancer genomics data,” said Max Leiserson, a Ph.D. student at Brown who led the development of the tool. “MAGI lets users explore these data in a regular web browser and with no computational expertise required.”

    In addition to viewing TCGA data, the portal also allows users to upload their own data and compare their findings to those in the larger databases.

    “Over the last decade, researchers working with TCGA have sequenced genes from thousands of tumors and dozens of cancer types in an effort to understand which mutations contribute to the development of cancer,” said Ben Raphael, director of Brown’s Center for Computational and Molecular Biology, who helped oversee the project. “At the same time, as sequencing has gotten faster and cheaper, individual researchers have begun sequencing samples from their own studies, sometimes from just a few tumors.”

    By uploading their data to MAGI, researchers can leverage the large public datasets to help interpret their own data.

    “In cancer genomics, there’s real value in large sample sizes because mutations are diverse and spread all over the genome,” Raphael said. “If I had just sequenced a few cancer genomes from my local tumor bank, one of the first things I’d want to do is compare my data to these big public datasets and look for similarities.”

    MAGI has data from TCGA already loaded. Users can search by cancer type, by individual genes, or by groups of genes. The output offers several ways of visualizing the search results, showing how often a given gene is mutated across samples, what types of mutations they were, and other information.

    Those same search and visualization capabilities are available for user-uploaded data, which enables researchers to look at their own data side-by-side with TCGA data. Users can also annotate TCGA data, appending new findings, academic papers and other relevant information.

    “When someone uploads data to MAGI, they can use the public data to help them interpret their own dataset,” Raphael said. “But in the process, they might also be able say something about the public data. We thought: wouldn’t it be great if users could record that information and share it?”

    The MAGI project started as a means of looking at the output from algorithms that Raphael’s lab develops. Those algorithms comb through large genome datasets, helping to pick out the mutations that are important to cancer development and distinguishing them from benign mutations that are just along for the ride.

    “As we were developing tools to visualize our own results, we realized that other researchers might also find these tools useful,” Raphael said. “We decided to develop a public portal for the cancer genomics research community.”

    The lab is making MAGI available for free, with the hope that many in the cancer genomics community will take advantage of it.

    “We think this could be a really useful piece of software,” Raphael said. “There’s great value in just being able to look at these data. We hope MAGI will lead to some new discoveries.”

    Other contributors included Ph.D. students Hsin-Ta Wu and Connor Gramazio, undergraduate Jason Hu, and David Laidlaw, professor of computer science.

    Raphael and his colleagues describe MAGI in a correspondence published in the June issue of Nature Methods. The work was supported by the National Institutes of Health (grants R01HG005690 and R01HG007069).

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

  • richardmitnick 8:44 am on May 13, 2015 Permalink | Reply
    Tags: , Cancer,   

    From Sandia: “Starving cancer instead of feeding it poison” 

    Sandia Lab

    May 13, 2015
    Neal Singer
    (505) 845-7078

    Sandia National Laboratories researcher Susan Rempe says a new approach to treating cancer is being tested on laboratory mice. If successful, human testing will follow. (Photo by Randy Montoya)

    A patent application for a drug that could destroy the deadly childhood disease known as acute lymphoblastic leukemia — and potentially other cancers as well — has been submitted by researchers at Sandia National Laboratories, the University of Maryland and the MD Anderson Cancer Center in Houston.

    “Most drugs have to go inside a cell to kill it,” said Sandia researcher Susan Rempe. “Instead, our method withholds an essential nutrient from the cell, essentially starving it until it self-destructs.”

    The removed nutrient is called asparagine, which cancer cells can’t produce on their own. But there’s more to the story.

    It’s well-known that chemical attempts using drugs to kill cancers often sicken the patient. In the case of the cancer drug L-asparaginase type 2 (L-ASN2), whose primary effect is depleting asparagine, side effects are generally attributed to the corresponding depletion of a chemically similar molecule called glutamine. All human cells need asparagine and glutamine to survive because each is essential to key biological processes. While most normal cells can synthesize their own asparagine, certain cancer cells cannot. So the ideal nutrient-deprivation strategy for cancers requires a difficult balancing act: Remove enough asparagine from the blood to cripple the cancer, but leave enough glutamine that the patient can tolerate chemotherapy.

    The researchers at Sandia and the university did molecular computer simulations to predict what mutations would produce that desirable result when introduced into the enzyme-drug L-ASN2, commonly used to treat certain types of leukemia. The scientists’ simulations succeeded in identifying a point in that enzyme’s chain of amino acids where a mutation theoretically would eliminate the drug’s unwanted attack on glutamine.

    “Technically,” said Rempe, “we simulated which parts of the two molecules came in contact with the enzyme. Then we realized that by substituting a single amino acid in the enzyme’s chain, we might avoid glutamine degradation by removing it from contact with the enzyme.”

    In computer simulations, the change looked promising because the most notable difference between asparagine and glutamine was the way they interacted with that specific amino acid.

    “That made us feel that a chemical change at that single location was the key,” said Rempe.

    It required a mutation to change the amino acid’s chemistry. The mutation was achieved by collaborators at MD Anderson who used DNA substitutions to effect the change.

    “Most researchers agree that removing glutamine from a patient’s blood was the problem in previous use of this enzyme-drug,” said Rempe. “Our simulations, as it turned out, showed how to avoid that.”

    In test tube experiments, the new drug left glutamine untouched. Follow-up tests in petri dishes showed that the mutated enzyme killed a variety of cancers.

    Tests underway on laboratory mice at MD Anderson should be completed by early 2016, and if they are successful, Rempe said, human testing will follow.

    A simulation by researchers at Sandia National Laboratories and the University of Maryland demonstrates that a mutated enzyme will degrade asparagine – food for some cancers — but leave glutamine, necessary for all proteins, untouched. (Graphic by Juan Vanegas)

    “If we’re wrong, and keeping glutamine intact is not the answer to the cancer problem, we’ll continue investigating because we think we’re onto something,” she said.

    That’s because, she said, “we used high-resolution computational methods to redesign the cancer drug to act differently, in this case to act only on asparagine. Laboratory tests showed that the predictions worked and that the new drug kills a variety of leukemias. We hope our method can do that in a patient, and for many more cancers. But if it doesn’t, then we’ll test the opposite strategy: redesign the enzyme to destroy glutamine and keep asparagine intact. Or fine-tune the enzyme to degrade the two molecules in a chosen ratio. We’re learning to control this enzyme.”

    The joint work among Sandia, the University of Maryland and MD Anderson began in 2009. Sandia managers Wahid Hermina and Steve Casalnuovo spearheaded the collaboration to use Sandia’s computational and biochemical expertise developed in national defense to help cure cancer.

    Sandia’s cancer-fighting research also can be applied to building enzymes that can assist with bio defense.

    Said Rempe, “If we could redesign an enzyme to break down specific small molecules, and not get diverted by interactions with non-toxic molecules, then we could apply our technique to develop safer and more effective enzymes.”

    Classical modeling was performed at the University of Maryland by Andriy Anishkin and Sergei Sukharev; at Sandia, post-doctoral researcher David Rogers (now at the University of South Florida) also carried out modeling studies. Sandia post-doctoral researcher Juan Vanegas is performing quantum modeling to map out the chemical degradation process to better understand how to optimize the enzyme, said Rempe. The experiments at MD Anderson were carried out by Wai Kin Chan, Phil Lorenzi, and colleagues in John Weinstein’s group. Earlier results have been published in the journal Blood.

    The work is supported by Sandia’s Laboratory Directed Research and Development office.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Sandia Campus
    Sandia National Laboratory

    Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies, and economic competitiveness.

  • richardmitnick 11:24 am on April 26, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From livescience: “Melanoma Tumor ‘Dissolves’ After 1 Dose of New Drug Combo” 


    April 24, 2015
    Laura Geggel

    A CT scan of the woman’s tumor highlighted by the asterisk (C) before treatment and after treatment (D).
    Credit: The New England Journal of Medicine, Copyright 2015

    A large melanoma tumor on a woman’s chest disappeared so quickly that it left a gaping hole in its place after she received a new treatment containing two melanoma drugs, a new case report finds.

    Doctors are still monitoring the 49-year-old woman, but she was free of melanoma — a type of skin cancer that can be deadly — at her last checkup, said the report’s lead author, Dr. Paul Chapman, an attending physician and head of the melanoma section at the Memorial Sloan Kettering Cancer Center in New York.

    The woman took the same two drugs as more than 100 people with melanoma who took part in a recent study. For most of the study participants who took these drugs, the combination worked better than one drug alone. But the doctors were surprised by how well the drug combination worked to treat this particular woman’s cancer — they had not anticipated that a melanoma tumor could disappear so quickly that it would leave a cavity in the body — and thus wrote the report describing her case.

    “What was unusual was the magnitude [of recovery], and how quickly it happened,” Chapman told Live Science. However, doctors are wary of the drug combination because it does not work for everyone, and can have side effects, such as severe diarrhea.

    Both the study of the drug combination and the woman’s case report were published Monday (April 20) in the New England Journal of Medicine. The drug combination is part of a relatively recent approach to treating melanoma with medications that boost a person’s own immune system, called immunotherapy.

    One of the drugs in the combination was ipilimumab (sold under the brand name Yervoy), which works by removing an inhibitory mechanism that can stop certain immune cells from killing cancer cells.

    In the study, researchers combined ipilimumab with another drug, called nivolumab (brand name Opdivo), which can prevent immune cells called T cells from dying, Chapman said.

    The U.S. Food and Drug Administration has approved ipilimumab and nivolumab separately as melanoma drugs but has not approved their combined use. The researchers’ study was aimed at testing how the two drugs worked when used in tandem.

    In the study, doctors gave treatments to 142 people with metastatic melanoma (melanoma that has spread to other parts of the body) — some participants received the combination, and others received ipilimumab plus a placebo. Neither the participants nor their doctors knew who had received which treatment until the trial had ended.

    A woman with melanoma developed a large tumor on her abdomen (A), but after one combination treatment of two immunotherapy drugs, it disappeared (B) within three weeks. Credit: The New England Journal of Medicine, Copyright 2015.

    The new drug combination had better results than the ipilimumab-plus-placebo treatment, the researchers found.

    In one analysis, the researchers focused on 109 patients who did not have a mutation in a gene called the BRAF gene. (BRAF mutations are linked to a number of cancers, including melanoma, and there are other melanoma drugs that target BRAF mutations.) Among the 72 people in this group who took the combination, 61 percent saw their cancer shrink, compared with just 11 percent of the 37 people in the group who took only ipilimumab.

    What’s more, melanoma was undetectable in 22 percent of the combination group at the end of the study, which was funded by Bristol-Myers Squibb, which makes the drugs. None of the people taking ipilimumab plus a placebo saw their melanoma disappear by the time the study had ended.

    Twenty-two percent may not sound high, but in the world of melanoma treatment, it is significant, said Dr. Sylvia Lee, an assistant professor of medicine at the University of Washington, Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center. Lee was not involved in the new study, but she is working with patients who are receiving the drug combination in Seattle.

    A complete response to treatment is “the Holy Grail,” she said. “That’s what everyone wants, where all of the cancer disappears. We’re talking about patients with stage IV melanoma. Usually, in cancers, when someone has stage IV disease, for the majority of people, it’s no longer curable.”

    It’s unclear whether melanoma will reoccur in any of the patients in the new study. Doctors are following them to see whether the people who are taking the combination drugs live longer than expected, Chapman said.

    Side effects

    However, the ipilimumab with nivolumab combination comes with serious side effects, such as colitis (swelling of the colon), diarrhea and problems with the endocrine glands (which produce hormones).

    About 54 percent of the patients in the study who were taking the combination reported serious side effects, compared with 24 percent of the people taking only ipilimumab, the researchers found.

    The treatments are given three weeks apart, but some people can tolerate only one or two treatments out of the suggested four before they stop taking the medicine, Lee said. In the new study, about 60 percent of the participants taking the combination finished all four treatments, compared with 70 percent of the ipilimumab-only group.

    The side effects can be brutal, Lee said. “This is diarrhea that is 25 to 40 times a day,” she said.

    Future trials may help researchers refine the number of treatments needed and figure out how effective just one or two treatments can be. The current trial is over, but certain cancer centers are still offering the drug combination through an expanded access program, which is how the woman whose tumor disappeared got the medicine.

    Her case shows that immunotherapy can work quickly: Her tumor vanished within three weeks of receiving her first treatment, the researchers found.

    “I was astonished; I’d never seen anything like that,” Chapman said. “She said the tumor had just kind of dissolved.”

    However, the combination may pose a risk if it dissolves a tumor somewhere else the body, and leaves a hole behind.

    “I think that it is a huge concern,” Lee said. “It is something to consider if you do have a patient with a tumor [invading] a vital organ.”

    The medications are also pricey. Ipilimumab costs $120,000 for four treatments, and nivolumab is priced at $12,500 a month, the Wall Street Journal reported.

    Still, the drug combination may offer a new and promising treatment for people with melanoma if the FDA approves it, Chapman said.

    “It kind of confirms an assumption that we’ve all had for many decades: that the immune system can recognize cancers and can kill large tumors if properly activated,” Chapman said.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

  • richardmitnick 1:09 pm on April 22, 2015 Permalink | Reply
    Tags: , Cancer,   

    From U Washington: “Study explores new avenues of breast cancer therapy” 

    U Washington

    University of Washington

    Michael McCarthy

    The protein landscape of aggressive forms of breast cancer are examine by molecular and cell biology researcher Robert Lawrence and Judit Villen, a genome scientist.

    An exhaustive analysis has been conducted of more than 12,000 distinct proteins present in an often aggressive and difficult to treat form of breast cancer, called triple-negative breast cancer.

    The results may help explain why these cancers often fail to respond to current drug treatments and may provide researchers with new targets for drug therapy.

    The researchers’ findings appear in this week’s issue of the journal Cell Reports. Robert Lawrence, a University of Washington graduate student in molecular and cellular biology, is the lead author of the article, The proteomic landscape of triple-negative breast cancer. Dr. Judit Villén, UW assistant professor of genome sciences, is the paper’s senior author.

    Triple-negative breast cancer cells have low levels of three receptors found in many breast cancers. Two receptors are for the hormones estrogen and progesterone and one receptor is for human epidermal growth factor receptor 2 or HER2.

    The study was performed in collaboration with the labs of Su-In Lee, assistant professor of genome sciences and of computer science and engineering, and Anthony Blau, director of the UW’s Center for Cancer Innovation. Both co-authored the study.

    About one in five breast cancers are triple-negative. They tend to be more aggressive and grow and spread more rapidly. They are also less likely to respond to many standard treatments. Triple-negative breast cancer occurs more often in women under age 40 and in African American women.

    In the new study, the researchers used a technique called mass spectrometry to identify and quantify the proteins being produced in twenty breast cell lines and four breast tumor samples. This process is called proteomic analysis. The study was performed in collaboration with the labs of Dr. C Anthony Blau, director of the UW’s Center for Cancer Innovation and Su-In Lee, assistant professor of genome sciences and of computer science and engineering, both co-authors on the study.

    Analysis of the mass spectrometry data revealed that subtypes within these cancer samples could be identified on the basis of the types of proteins they expressed and the quantity of those proteins.

    “In terms of the protein expression, even within these subtypes, the cells are very different from one another, which suggests they will behave differently and respond to treatment differently,” Lawrence said.

    To further explore the relationship between genes, proteins and drug response, the researchers correlated their proteomic findings with existing genomic databases and conducted drug sensitivity tests on 16 of the cell lines.

    Their findings suggested why one drug that might work in one case of triple-negative cancers might fail to work on another. For example, the researchers found that some of the triple-negative breast cancer cells produced low levels of proteins involved in cell proliferation while producing high levels of proteins that allow cells to spread. Because most conventional chemotherapy targets pathways that promote proliferation, these cells would likely be able to resist standard treatments. Treatments that target the means by which the cancer spreads may, therefore, prove more effective against triple-negative breast cancers that resist conventional therapy.

    To make their findings available to other researchers, the UW team has created a website (https://zucchini.gs.washington.edu/BreastCancerProteome/) where the new proteomic and drug sensitivity findings as well as genomic data can be accessed.

    “We want this to be a resource for researchers everywhere,” Villén said. “Investigators will be able to go to the site and type in the name of their protein of interest and see how it is expressed in these cells. Or they can type in the name of a drug and see which genes and proteins are associated with the tumor’s sensitivity or resistance to the drug.”

    Villén expects in the coming year that proteomic analysis will be used in clinical trials, such as the Center for Cancer Innovation’s clinical trial in metastatic triple negative breast cancer.. Currently, using mass spectrometry, her lab can analyze a tumor sample in 24 hours. She expects that once researchers determine the 100 or so most important proteins, a tissue sample could be tested in just an hour. This analysis will provide a more detailed diagnostics of breast tumors, and may offer novel therapeutic avenues for resistant tumors.

    In addition to Blau, Lawrence, Lee and Villén, co-authors were Elizabeth M. Perez, Daniel Hernández and Kelsey M Haas, of the UW Department of Genome Sciences, Chris P. Miller of the UW Center for Cancer Innovation and Hanna Y. Irie of the Icahn School of Medicine, Mount Sinai, in New York City.

    The research was supported by Howard Temin Pathway to Independence Award K99/R00 from the National Cancer Institute at the National Institutes of Health (R00CA140789); a National Science Foundation grant (DBI-1355899); and funds from the South Sound CARE Foundation, the Washington Research Foundation, and the Gary E. Milgard Family Foundation.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    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 8:16 am on April 16, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From Harvard: “Faster, Cheaper Testing” 

    Harvard University

    Harvard University

    April 13, 2015

    By quantifying the number of tumor-marker-targeting microbeads bound to cells (lower images), the D3 system categorizes high- and low-risk cervical biopsy samples as accurately as traditional pathology (upper images). Image: Massachusetts General Hospital Center for Systems Biology

    A device developed by Harvard Medical School investigators at Massachusetts General Hospital may bring rapid, accurate molecular diagnosis of cancer and other diseases to locations lacking the latest medical technology.

    In their report appearing in PNAS Early Edition, the researchers describe a smartphone-based device that uses technology for making holograms to collect detailed microscopic images for digital analysis of the molecular composition of cells and tissues.

    “The global burden of cancer, limited access to prompt pathology services in many regions and emerging cell profiling technologies increase the need for low-cost, portable and rapid diagnostic approaches that can be delivered at the point of care,” said Cesar Castro, HMS instructor in medicine at Mass General and co-lead author of the report. “The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy, supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators and patients. We believe the platform we have developed provides essential features at an extraordinary low cost.”

    The device—called the D3 (digital diffraction diagnosis) system—features an imaging module with a battery-powered LED light clipped onto a standard smartphone. It records high-resolution imaging data with its camera.

    With a much greater field of view than traditional microscopy, the D3 system is capable of recording data on more than 100,000 cells from a blood or tissue sample in a single image. The data can then be transmitted for analysis to a remote graphic-processing server via a secure, encrypted cloud service. The results can be rapidly returned to the point of care.

    For molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules; the sample is then loaded into the D3 imaging module. After the image is recorded and data transmitted to the server, the presence of specific molecules is detected by analyzing the diffraction patterns generated by the microbeads.

    The use of variously sized or coated beads may offer unique diffraction signatures to facilitate detection. A numerical algorithm developed by the research team for the D3 platform can distinguish cells from beads and analyze as much as 10 MB of data in less than nine-hundredths of a second.

    A pilot test of the system with cancer cell lines detected the presence of tumor proteins with an accuracy matching the current gold standard for molecular profiling. The larger field of view enabled simultaneous analysis of more than 100,000 cells at a time.

    The investigators then conducted analysis of cervical biopsy samples from 25 women with abnormal Pap smears—samples collected along with those used for clinical diagnosis—using microbeads tagged with antibodies against three published markers of cervical cancer.

    Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk or benign, with results matching conventional pathologic analysis.

    D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate four patients whose lymphoma diagnosis was confirmed by conventional pathology from another four with benign lymph node enlargement. Along with protein analyses, the system was enhanced to successfully detect DNA—in this instance from human papillomavirus—with great sensitivity.

    In these pilot tests, results of the D3 assay were available in under an hour and at a cost of $1.80 per assay, a price that would be expected to drop with further refinement of the system.

    “We expect that the D3 platform will enhance the breadth and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings,” said Ralph Weissleder, HMS Thrall Family Professor of Radiology at Mass General, director of the Mass General Center for Systems Biology and co-senior author of the paper. “By taking advantage of the increased penetration of mobile phone technology worldwide, the system should allow the prompt triaging of suspicious or high-risk cases. That could help to offset delays caused by limited pathology services in those regions and reduce the need for patients to return for follow-up care, which is often challenging for them.”

    In their further development of this technology, co-senior author Hakho Lee, HMS assistant professor of radiology at Mass General, noted, “The research team will investigate the D3 platform’s ability to analyze protein and DNA markers of other disease catalysts, including infectious agents and allergens, integrate the software with larger databases and conduct clinical studies in settings such as care-delivery sites in developing countries or rural settings and for home testing with seamless sharing of information with providers and/or clinical investigators.”

    Mass General has filed a patent application covering the D3 technology.

    “Compared with traditional analysis techniques, the D3 mobile platform generates robust biological data while being significantly more cost-conscious, operable by nonspecialist end users and well-suited to point-of-care settings,” said co-lead author Hyungsoon Im, HMS research fellow in radiology at Mass General. “We have field tested the wireless readouts in rural areas of northern New England without problems and believe this technology is poised to deliver fast, low-cost and accurate cancer and HPV diagnosis.”

    The study was supported by National Institutes of Health grants R01-HL113156, R01-EB010011, R01-EB00462605A1, T32CA79443 and K12CA087723-11A1; National Heart, Lung and Blood Institute contract HHSN268201000044C; and Department of Defense Ovarian Cancer Research Program Award W81XWH-14-1-0279.

    See the full article here.

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

  • richardmitnick 7:33 pm on April 15, 2015 Permalink | Reply
    Tags: , Cancer, ,   

    From isgtw: “Supercomputing enables researchers in Norway to tackle cancer” 

    international science grid this week

    April 15, 2015
    Yngve Vogt

    Cancer researchers are using the Abel supercomputer at the University of Oslo in Norway to detect which versions of genes are only found in cancer cells. Every form of cancer, even every tumour, has its own distinct variants.

    “This charting may help tailor the treatment to each patient,” says Rolf Skotheim, who is affiliated with the Centre for Cancer Biomedicine and the research group for biomedical informatics at the University of Oslo, as well as the Department of Molecular Oncology at Oslo University Hospital.

    Temp 0
    “Charting the versions of the genes that are only found in cancer cells may help tailor the treatment offered to each patient,” says Skotheim. Image courtesy Yngve Vogt.

    His research group is working to identify the genes that cause bowel and prostate cancer, which are both common diseases. There are 4,000 new cases of bowel cancer in Norway every year. Only six out of ten patients survive the first five years. Prostate cancer affects 5,000 Norwegians every year. Nine out of ten survive.

    Comparisons between healthy and diseased cells

    In order to identify the genes that lead to cancer, Skotheim and his research group are comparing genetic material in tumours with genetic material in healthy cells. In order to understand this process, a brief introduction to our genetic material is needed:

    Our genetic material consists of just over 20,000 genes. Each gene consists of thousands of base pairs, represented by a specific sequence of the four building blocks, adenine, thymine, guanine, and cytosine, popularly abbreviated to A, T, G, and C. The sequence of these building blocks is the very recipe for the gene. Our whole DNA consists of some six billion base pairs.

    The DNA strand carries the molecular instructions for activity in the cells. In other words, DNA contains the recipe for proteins, which perform the tasks in the cells. DNA, nevertheless, does not actually produce proteins. First, a copy of DNA is made: this transcript is called RNA and it is this molecule that is read when proteins are produced.

    RNA is only a small component of DNA, and is made up of its active constituents. Most of DNA is inactive. Only 1–2 % of the DNA strand is active.

    In cancer cells, something goes wrong with the RNA transcription. There is either too much RNA, which means that far too many proteins of a specific type are formed, or the composition of base pairs in the RNA is wrong. The latter is precisely the area being studied by the University of Oslo researchers.

    Wrong combinations

    All genes can be divided into active and inactive parts. A single gene may consist of tens of active stretches of nucleotides (exons). “RNA is a copy of a specific combination of the exons from a specific gene in DNA,” explains Skotheim. There are many possible combinations, and it is precisely this search for all of the possible combinations that is new in cancer research.

    Different cells can combine the nucleotides in a single gene in different ways. A cancer cell can create a combination that should not exist in healthy cells. And as if that didn’t make things complicated enough, sometimes RNA can be made up of stretches of nucleotides from different genes in DNA. These special, complex genes are called fusion genes.

    Temp 0
    “We need powerful computers to crunch the enormous amounts of raw data,” says Skotheim. “Even if you spent your whole life on this task, you would not be able to find the location of a single nucleotide.”

    In other words, researchers must look for errors both inside genes and between the different genes. “Fusion genes are usually found in cancer cells, but some of them are also found in healthy cells,” says Skotheim. In patients with prostate cancer, researchers have found some fusion genes that are only created in diseased cells. These fusion genes may then be used as a starting-point in the detection of and fight against cancer.

    The researchers have also found fusion genes in bowel cells, but they were not cancer-specific. “For some reason, these fusion genes can also be found in healthy cells,” adds Skotheim. “This discovery was a let-down.”
    Improving treatment

    There are different RNA errors in the various cancer diseases. The researchers must therefore analyze the RNA errors of each disease.

    Among other things, the researchers are comparing RNA in diseased and healthy tissue from 550 patients with prostate cancer. The patients that make up the study do not receive any direct benefits from the results themselves. However, the research is important in order to be able to help future patients.

    “We want to find the typical defects associated with prostate cancer,” says Skotheim. “This will make it easier to understand what goes wrong with healthy cells, and to understand the mechanisms that develop cancer. Once we have found the cancer-specific molecules, they can be used as biomarkers.” In some cases, the biomarkers can be used to find cancer, determine the level of severity of the cancer and the risk of spreading, and whether the patient should be given a more aggressive treatment.

    Even though the researchers find deviations in the RNA, there is no guarantee that there is appropriate, targeted medicine available. “The point of our research is to figure out more of the big picture,” says Skotheim. “If we identify a fusion gene that is only found in cancer cells, the discovery will be so important in itself that other research groups around the world will want to begin working on this straight away. If a cure is found that counteracts the fusion genes, this may have enormous consequences for the cancer treatment.”

    Laborious work

    Recreating RNA is laborious work. The set of RNA molecules consists of about 100 million bases, divided into a few thousand bases from each gene.

    The laboratory machine reads millions of small nucleotides. Each one is only 100 base pairs long. In order for the researchers to be able to place them in the right location, they must run large statistical analyses. The RNA analysis of a single patient can take a few days.

    All of the nucleotides must be matched with the DNA strand. Unfortunately the researchers do not have the DNA strands of each patient. In order to learn where the base pairs come from in the DNA strand, they must therefore use the reference genome of the human species. “This is not ideal, because there are individual differences,” explains Skotheim. The future potentially lies in fully sequencing the DNA of each patient when conducting medical experiments.

    There is no way this research could be carried out using pen and paper. “We need powerful computers to crunch the enormous amounts of raw data. Even if you spent your whole life on this task, you would not be able to find the location of a single nucleotide. This is a matter of millions of nucleotides that must be mapped correctly in the system of coordinates of the genetic material. Once we have managed to find the RNA versions that are only found in cancer cells, we will have made significant progress. However, the work to get that far requires advanced statistical analyses and supercomputing,” says Skotheim.

    The analyses are so demanding that the researchers must use the University of Oslo’s Abel supercomputer, which has a theoretical peak performance of over 250 teraFLOPS. “With the ability to run heavy analyses on such large amounts of data, we have an enormous advantage not available to other cancer researchers,” explains Skotheim. “Many medical researchers would definitely benefit from this possibility. This is why they should spend more time with biostatisticians and informaticians. RNA samples are taken from the patients only once. The types of analyses that can be run are only limited by the imagination.”

    “We need to be smart in order to analyze the raw data.” He continues: “There are enormous amounts of data here that can be interpreted in many different ways. We just got started. There is lots of useful information that we have not seen yet. Asking the right questions is the key. Most cancer researchers are not used to working with enormous amounts of data, and how to best analyze vast data sets. Once researchers have found a possible answer, they must determine whether the answer is chance or if it is a real finding. The solution is to find out whether they get the same answers from independent data sets from other parts of the world.”

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    iSGTW is an international weekly online publication that covers distributed computing and the research it enables.

    “We report on all aspects of distributed computing technology, such as grids and clouds. We also regularly feature articles on distributed computing-enabled research in a large variety of disciplines, including physics, biology, sociology, earth sciences, archaeology, medicine, disaster management, crime, and art. (Note that we do not cover stories that are purely about commercial technology.)

    In its current incarnation, iSGTW is also an online destination where you can host a profile and blog, and find and disseminate announcements and information about events, deadlines, and jobs. In the near future it will also be a place where you can network with colleagues.

    You can read iSGTW via our homepage, RSS, or email. For the complete iSGTW experience, sign up for an account or log in with OpenID and manage your email subscription from your account preferences. If you do not wish to access the website’s features, you can just subscribe to the weekly email.”

  • richardmitnick 5:31 am on April 11, 2015 Permalink | Reply
    Tags: , Cancer,   

    From MedicalXpress: “Telomeres and cancer mortality: The long and the short of it” 

    Medicalxpress bloc


    April 10, 2015
    No Writer Credit

    Human chromosomes (grey) capped by telomeres (white). Credit: PD-NASA; PD-USGOV-NASA

    Telomeres are short stretches of repeated nucleotides that protect the ends of chromosomes. In somatic cells, these protective sequences become shorter with each cellular replication until a critical length is reached, which can trigger cell death.

    In actively replicating cells such as germ cells, embryonic stem cells, and blood stem cells of the bone marrow, the enzyme telomerase replenishes these protective caps to ensure adequate replication. Cancer cells also seem to have the ability to activate telomerase, which allows them to keep dividing indefinitely, with dire consequences for the patient. However, according to a study published April 10 in the JNCI: Journal of the National Cancer Institute, the extent to which cancer cells can utilize telomerase may depend on which variants of the genes related to telomerase activity are expressed in an individual’s cells.

    Telomere shortening is an inevitable, age-related process, but it can also be exacerbated by lifestyle factors such as obesity and smoking. Thus, some previous studies have found an association between short telomeres and high mortality, including cancer mortality, while others have not. A possible explanation for the conflicting evidence may be that the association found between short telomeres and increased cancer mortality was correlational but other factors (age and lifestyle), not adjusted for in previous studies, were the real causes. Genetic variation in several genes associated with telomere length (TERC, TERT, OBFC1) is independent of age and lifestyle. Thus, a genetic analysis called a Mendelian randomization could eliminate some of the confounding and allow the presumably causal association of telomere length and cancer mortality to be studied.

    To perform this analysis, Line Rode, M.D., Ph.D., of the Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, and colleagues, used data from two prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, including 64,637 individuals followed from 1991-2011. Participants completed a questionnaire and had a physical examination and blood drawn for biochemistry, genotyping, and telomere length assays.

    For each subject, the authors had information on physical characteristics such as body mass index, blood pressure, and cholesterol measurements, as well as smoking status, alcohol consumption, physical activity, and socioeconomic variables. In addition to the measure of telomere length for each subject, three single nucleotide polymorphisms of TERC, TERT, and OBFC1 were used to construct a score for the presence of telomere shortening alleles.

    A total of 7607 individuals died during the study, 2420 of cancer. Overall, as expected, decreasing telomere length as measured in leukocytes was associated with age and other variables such as BMI and smoking and with death from all causes, including cancer. Surprisingly, and in contrast, a higher genetic score for telomere shortening was associated specifically with decreased cancer mortality, but not with any other causes of death, suggesting that the slightly shorter telomeres in the cancer patients with the higher genetic score for telomere shortening might be beneficial because the uncontrolled cancer cell replication that leads to tumor progression and death is reduced.

    The authors conclude, “We speculate that long telomeres may represent a survival advantage for cancer cells, allowing multiple cell divisions leading to high cancer mortality.”

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    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 5:10 am on April 11, 2015 Permalink | Reply
    Tags: , Cancer,   

    From Technion via Haaretz: “Preliminary results from Israeli study: Cannabis delays cancer development” 

    Technion bloc


    Haaretz bloc

    Ido Efrati

    New research shows – with cautious optimism – that cannabis can kill or slow the development of cancer cells.

    A worker touches a cannabis plant at a growing facility for the Tikun Olam company near the northern city of Safed August 22, 2010 Photo by Reuters

    Medical cannabis is well known to cancer patients. A large number of Israelis receive it as part of their palliative care for dealing with the symptoms of the disease, as cannabis has been found to be effective in relieving chronic pain, nausea and loss of appetite.

    Scientists from the Technion-Israel Institute of Technology in Haifa have been researching completely different possibilities for the use of cannabis by cancer patients – as an active treatment against the development of the disease itself. A precedent-setting study examined how dozens of strains of cannabis affect the development and growth of hundreds of types of cancer cells.

    This study is one of the first signs of a new approach to the use of cannabis in cancer treatment, which examines whether the plant can help in delaying the development of cancerous growths – or even eliminate them completely.

    The preliminary results, which were found in the first few weeks of the research, show that cannabis is quite possibly effective in treating brain and breast cancers.

    Dr. David Meiri, an assistant professor in the biology department at the Technion, is leading the cancer research team. Meiri, the head of Technion’s Laboratory of Cancer Biology and Cannabinoid Research who did postdoctoral work at the Ontario Cancer Institute in Toronto, opened his lab in the Technion about a year ago.

    Meiri specializes in studying the cytoskeleton of cells, which is a critical component of the processes of division and movement of cancer cells, and of all cells in general. Meiri told Haaretz that he searched for all sorts of materials that affect the structure of the cell in his research in Toronto, and found cannabis. The deeper he went into the field, the more he realized there was a huge vacuum and lack of scientific knowledge about the effects of cannabis.

    There are very few studies on cannabis and brain cancer, he noted. Meiri approached this in two ways: Whether cannabis is capable of keeping cancer cells from becoming virulent, and at the same time studying how far cannabis can go in fighting the cancer cells themselves – and possibly destroy them.

    The connection between the cannabis plant and the various cancers is an interesting question in its own right, but it also produces an almost unlimited statistical expanse for study. Today, scientists are examining some 50 different varieties of the plant produced in Israel, and studying its effects on some 200 different types of cancer cells.

    Another variable has to be taken into account: the way the cannabis is applied, which can significantly affect its effectiveness. Even if we take the most basic separation between the varieties of the plant, we still do not know how the way it is ingested affects the cell, says Meiri. Take, for example, cannabis extract produced using ethanol compared to that produced using carbon dioxide, since there are differences between the cells of various forms of cancer – so the research potential is infinite – and that is what Meiri says attracts him to the subject.

    Practical pharmaceutical hopes

    The research project is part of a joint research agreement between the Technion and Cannabics Pharmaceuticals, an emerging American drug company, signed last week. As its name infers, Cannabics is interested in drugs based on cannabis and sells cannabis capsules for cancer patients. Cannabics will provide the various strains of the plants for the research. The company is traded over the counter in the United States.

    Cannabics Pharmaceuticals focuses on the development and commercialization of advanced drugs, therapies, food supplements and administration routes based on the wide range of active ingredients found in diverse and unique strains of the Cannabis plant.

    The collaborative research project is meant to develop a diagnostic system that screens the anti-cancer properties of cannabis-based active ingredients. This system will be harnessed to explore different types of cancer cells treated with a multitude of cannabinoid combinations.

    “There is a large body of scientific data which indicates that cannabinoids specifically inhibit cancer cell growth and promote cancer cell death,” explained Meiri. “In addition to active cannabinoids, cannabis plants also contain a multitude of other therapeutic agents, such as terpenoids and flavonoids that are usually present in small quantities, but can have beneficial therapeutic effects, especially as synergistic compounds to cannabinoids.”

    Cannabics’ current flagship product is Cannabics SR an patent-pending medical cannabis capsule designed specifically for cancer patients as a palliative care treatment. Cannabics is now preparing to launch its line of SR products in eligible states of the U.S. and EU markets under existing medical cannabis regulatory pathways, while simultaneously launching a formal clinical study in order to establish the unique medical benefits of its SR capsules.

    The company is expected to start another study at the Rambam Medical Center in Haifa soon, which is intended on examining the effect of cannabis capsules on the loss of appetite and weight loss in cancer patients.

    “Cannabinoid based anticancer medicine could be a potent therapy without the side effects related to chemotherapy,” said Dr. Eyal Ballan, the chief scientist of Cannabics. Everyone is waiting and hoping for significant results from the research, he said.

    A miracle cure or dangerous drug?

    The medical discourse over the cannabis plant moves between two extremes: those who view it as a miracle drug and attribute numerous medical qualities – sometimes based only on anecdotal and not scientific evidence – and those who still see it as a dangerous and illegal drug with harmful effects in all cases. Obviously, both sides are exaggerating, but the real question is where the truth falls – and close to which side.

    From 1850 through 1937 cannabis – which has over 400 active ingredients – was used as a medicinal herb and was accepted in conventional medicine. Before that it was used in many cultures for thousands of years, such as in Chinese medicine, in which it is used to treat over 100 illnesses.

    The change in the attitude toward the use of the plant started in the early 1900s, and culminated in the late 1930s in the United States with its complete legal ban.

    Drug companies have also shown very little interest in the plant and ingredients, both because of its status as a controlled substance, but also because it is very hard to patent drugs from a natural plant, and it would be possible only to patent the various new forms of treatment. But things have changed in recent years and some drug companies, as well as scientists, have shown renewed interest in both the drug and treatments based on cannabis.

    The whole field of cannabis research is almost virgin territory from a scientific perspective, and there are relatively few experts in it today. Given all the changes in the field, it is doubtful whether an institution like the Technion would have been interested in such research even just a few years ago.

    Cautious optimism, not a marijuana missionary

    The real question for Meiri is how realistic are all these high expectations for cannabis as a cancer treatment? He would prefer to be asked the question in another year, and not at the initial stages of his research. But he is certainly pleased that the work has started off well.

    Meiri and his colleagues have succeeded in causing brain cancer cells to “commit suicide,” or apoptosis, a form of “programmed cell death.” This is something a group of Spanish researchers has seen in the past, and Meiri has been able to reproduce it.

    One of the characteristics of cancer cells is their ability to evade the cell’s mechanisms of death, and it seems cannabis somehow succeeds in putting this mechanism back into operation, even if the researchers still do not understand how, says Meiri. They have succeeded in producing similar results in breast cancer cells, and from there he wants to continue on to the other types of cancer.

    The preliminary results have given Meiri a reason for cautious optimism, but not much more than that. He certainly has not become a marijuana missionary.

    “Many businesspeople deal with and say things about cannabis. It seems some of them are overdoing it. I think it is now the turn of science to put things in order and find out how it helps, who it helps and exactly how it does so,” he says.

    Even if it helps with five or six types of cancer, it will be a success, but he doesn’t want to put the cart before the horse, says Meiri.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Technion Campus

    A science and technology research university, among the world’s top ten,
    dedicated to the creation of knowledge and the development of human capital and leadership,
    for the advancement of the State of Israel and all humanity.

  • richardmitnick 12:18 pm on April 10, 2015 Permalink | Reply
    Tags: , Cancer, , ,   

    From LBL: “New target for anticancer drugs: RNA” 

    UC Berkeley

    UC Berkeley

    April 6, 2015
    Robert Sanders

    DNA is transcribed into mRNA, which is then translated by ribosomes into proteins. UC Berkeley researchers demonstrated that dysregulation of the gene expression program governed by a ribosomal protein called eIF3 leads to increased cell growth and carcinogenesis. That makes this protein an ideal anticancer drug target. (Amy Lee graphic)

    Most of today’s anticancer drugs target the DNA or proteins in tumor cells, but a new discovery by University of California, Berkeley, scientists unveils a whole new set of potential targets: the RNA intermediaries between DNA and proteins.

    This RNA, called messenger RNA, is a blueprint for making proteins. Messenger RNA is created in the nucleus and shuttled to the cell cytoplasm to hook up with protein-making machinery, the ribosome. Most scientists have assumed that these mRNA molecules are, aside from their unique sequences, generic, with few distinguishing characteristics that could serve as an Achilles heel for targeted drugs.

    Jamie Cate, UC Berkeley professor of molecular and cell biology, and postdoctoral fellows Amy Lee and Philip Kranzusch have found, however, that a small subset of these mRNAs – most of them coding for proteins linked in some way to cancer – carry unique tags. These short RNA tags bind to a protein, eIF3 (eukaryotic initiation factor 3), that regulates translation at the ribosome, making the binding site a promising target.

    “We’ve discovered a new way that human cells control cancer gene expression, at the step where the genes are translated into proteins. This research puts on the radar that you could potentially target mRNA where these tags bind with eIF3,” Cate said. “These are brand new targets for trying to come up with small molecules that might disrupt or stabilize these interactions in such a way that we could control how cells grow.”

    These tagged mRNAs – fewer than 500 out of more than 10,000 mRNAs in a cell – seem to be special in that they carry information about specific proteins whose levels in the cell must be delicately balanced so as not to tip processes like cell growth into overdrive, potentially leading to cancer.

    Surprisingly, while some of the tags turn on the translation of mRNA into protein, others turn it off.

    “Our new results indicate that a number of key cancer-causing genes – genes that under normal circumstances keep cells under control – are held in check before the proteins are made,” Cate said. “This new control step, which no one knew about before, could be a great target for new anticancer drugs.

    “On the other hand,” he said, “the tags that turn on translation activate genes that cause cancer when too much of the protein is made. These could also be targeted by new anticancer drugs that block the activation step.”

    The new results will be reported April 6 in an advance online publication of the journal Nature. Cate directs the Center for RNA Systems Biology, a National Institutes of Health-funded group developing new tools to study RNA, a group of molecules increasingly recognized as key regulators of the cell.

    mRNA a messenger between DNA and ribosome

    While our genes reside inside the cell’s nucleus, the machinery for making proteins is in the cytoplasm, and mRNA is the messenger between the two. All the DNA of a gene is transcribed into RNA, after which nonfunctional pieces are snipped out to produce mRNA. The mRNA is then shuttled out of the nucleus to the cytoplasm, where a so-called initiation complex gloms onto mRNA and escorts it to the ribosome. The ribosome reads the sequence of nucleic acids in the mRNA and spits out a sequence of amino acids: a protein.

    “If something goes out of whack with a cell’s ability to know when and where to start protein synthesis, you are at risk of getting cancer, because you can get uncontrolled synthesis of proteins,” Cate said. “The proteins are active when they shouldn’t be, which over-stimulates cells.”

    The protein eIF3 is one component of the initiation complex, and is itself made up of 13 protein subunits. It was already known to regulate translation of the mRNA into protein in addition to its role in stabilizing the structure of the complex. Overexpression of eIF3 also is linked to cancers of the breast, prostate and esophagus.

    “I think eIF3 is able to drive multiple functions because it consists of a large complex of proteins,” Lee said. “This really highlights that it is a major regulator in translation rather than simply a scaffolding factor.”

    Lee zeroed in on mRNAs that bind to eIF3, and found a way to pluck them out of the 10,000+ mRNAs in a typical human cell, sequenced the entire set and looked for eIF3 binding sites. She discovered 479 mRNAS – about 3 percent of the mRNAs in the cell – that bind to eIF3, and many of them seem to share similar roles in the cell.

    “When we look at the biological functions of these mRNAs, we see that there is an emphasis on processes that become dysregulated in cancer,” Lee said. These involve the cell cycle, the cytoskeleton, and programmed cell death (apoptosis), along with cell growth and differentiation.

    “Therapeutically, one could screen for increased expression of eIF3 in a cancer tissue and then target the pathways that we have identified as being eIF3-regulated,” she said.

    Lee actually demonstrated that she could tweak the mRNA of two cancer-related genes, both of which control cell growth, to stop cells from becoming invasive.

    “We showed that we could put a damper on invasive growth by manipulating these interactions, so clearly this opens the door to another layer of possible anticancer therapeutics that could target these RNA-binding regions,” Cate said.

    The work was funded by a grant from NIH’s National Institute of General Medical Sciences to the Center for RNA Systems Biology.

    “A goal of systems biology is to map entire biological networks, such as genes and their regulatory mechanisms, to better understand how those complex networks function and can contribute to disease,” said Peter Preusch, chief of the biophysics branch of NIGMS. “This center is using cutting-edge technology to interrogate the structure and function of many RNAs at a time, which is helping piece together RNA’s regulatory components.”

    Lee is supported through the American Cancer Society Postdoctoral Fellowship Program.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Founded in the wake of the gold rush by leaders of the newly established 31st state, the University of California’s flagship campus at Berkeley has become one of the preeminent universities in the world. Its early guiding lights, charged with providing education (both “practical” and “classical”) for the state’s people, gradually established a distinguished faculty (with 22 Nobel laureates to date), a stellar research library, and more than 350 academic programs.

    UC Berkeley Seal

Compose new post
Next post/Next comment
Previous post/Previous comment
Show/Hide comments
Go to top
Go to login
Show/Hide help
shift + esc

Get every new post delivered to your Inbox.

Join 455 other followers

%d bloggers like this: