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  • richardmitnick 12:45 pm on January 17, 2017 Permalink | Reply
    Tags: , Cancer, ,   

    From Vanderbilt: “Softening tumor tissue could aid cancer treatments” 

    Vanderbilt U Bloc

    Vanderbilt University

    Jan. 16, 2017
    Liz Entman

    Softening tumors’ blood vessels may help more chemo reach the cancer

    Normally, the glue that holds cells together in the human body – what scientists call the extracellular matrix – is soft and pliable. But when a metastatic tumor forms it causes the matrix surrounding it to stiffen.

    According to a new study, this mechanical effect produces changes in the blood vessels that feed the tumor in a way that can reduce the effectiveness of chemotherapeutics and radiation treatments. The finding suggests that softening this protective layer could make existing cancer treatments more effective.

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    Cynthia Reinhart-King (Steve Green/Vanderbilt)

    The study was published Dec. 22 in the Proceedings of the National Academy of Sciences, by a team of researchers led by Vanderbilt Professor of Biomedical Engineering Cynthia Reinhart-King, which includes postdoctoral researcher François Bordeleau in the Reinhart-King group along with collaborators from Cornell University. The report is titled Matrix Stiffening Promotes a Tumor Vasculature Phenotype.

    For years, the idea has been that the way to treat tumors was to starve them by killing off their blood vessels. While that works in some cases, in others it only serves to make the tumor more aggressive, Reinhart-King said, adding: “There are ways tumors can grow in the absence of those nutrients, and they get more aggressive. At the same time, they may also stop responding to some chemotherapeutics and radiation treatments.”

    A metastatic tumor’s blood vessels tend to be malformed and more permeable than blood vessels in healthy tissue. For this reason, fluid tends to leak from the vessels, building up pressure inside the tumor that prevents drugs from getting to their target.

    “Basically, as fluid leaks out of the blood vessels, it causes high pressures to build up in the tumor. These high pressures can cause blood flow to stall or even reverse and vessels tocollapse,” Reinhart-King said. “So fluid, including the drugs, cannot reach the tumor tissue.”

    3
    Image of a mammary tumor stained for cell nuclei (in blue), blood vessels (in green) and the protein beta-catenin that causes cells to stick together (in red) (Reinhart-King Lab / Vanderbilt)

    Unlike in previous work in this area, Reinhart-King and Bordeleau see the vascular breakdown as a product of the stiffening of the tumor and its matrix, which triggers proteins in cells to alter vascular growth and integrity. Previous work has targeted chemical factors, in particular vascular endothelial growth factor.

    “The idea that you would want to restore barrier integrity and help blood vessels is not a new one,” Reinhart-King said. “The idea that we discovered is that it’s controlled through matrix stiffness.” This, in turn, suggests that promoting healthy vasculature through a softening of the extracellular matrix would use the tumor itself as a conduit for delivering cancer-killing drugs.

    “What we show,” Reinhart-King said, “is that we can drive a lot of the same behaviors that are typically thought to occur due to chemical changes, by changing the mechanical properties of the tumor.”

    This work was supported by National Institutes of Health grants R01-HL127499 and R01-CA163255 and National Science Foundation awards 1055502 and 435755.

    See the full article here .

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    Vanderbilt Campus

     
  • richardmitnick 9:00 am on January 11, 2017 Permalink | Reply
    Tags: , Cancer, ,   

    From Hopkins: “Johns Hopkins scientists zero in on how cancers resist immunotherapy treatment” 

    Johns Hopkins
    Johns Hopkins University

    Jan 6 2017
    Vanessa Wasta

    Results of an initial study of tumors from patients with certain cancers shed light on the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors.

    The study, conducted by researchers on five patients at the Johns Hopkins Kimmel Cancer Center, suggests the resistance is due to the elimination of certain genetic mutations that enable the immune system to recognize and attack malignant cells. The results of their research is described online in Cancer Discovery.

    “Checkpoint inhibitors are one of the most exciting recent advances for cancers, but the mechanism by which most patients become resistant to these therapies has been a mystery,” says Victor E. Velculescu, program leader in the Bloomberg–Kimmel Institute for Cancer Immunotherapy at Johns Hopkins and professor of oncology.

    Checkpoint inhibitors help the immune system recognize cancer cells by revealing evidence of mutated proteins called neoantigens on the surface of cancer cells. Clinical trials have shown that nearly half of patients with lung cancers eventually develop resistance to this class of drugs for reasons that have been unclear.

    To investigate why checkpoint inhibitors so often stop working, Velculescu joined Valsamo Anagnostou, instructor of oncology at the Johns Hopkins University School of Medicine; Kellie N. Smith, a cancer immunology research associate at the Johns Hopkins University School of Medicine; and their colleagues at the Bloomberg–Kimmel Institute for Cancer Immunotherapy.

    The team studied tumors of four patients with non-small cell lung cancer and one patient with head and neck cancer who developed resistance to two different checkpoint inhibitors: a drug called nivolumab that can be used alone or in combination with the second drug, ipilimumab.

    Using biopsies of the patients’ tumors collected before the start of treatment and at the time patients developed resistance, the researchers performed large-scale genomic analyses to search for mutations specific to the cancer cells in all of each patient’s 20,000 genes.

    The search uncovered genes that code for the production of antigens, which serve as a source of identification to the immune system. Cancer cells may contain mutations in genes that code for antigens, producing misshapen or otherwise altered antigens that scientists call neoantigens. Such neoantigens are foreign to the immune system, and thus, the cancer cell is flagged for destruction, usually with the help of immunotherapy drugs.

    The scientists found that after the patients developed resistance to immunotherapy, all of their tumors had shed between seven and 18 mutations in neoantigen-coding genes. By getting rid of those mutations, the tumor cells’ neoantigens look less foreign to the immune system and may go unrecognized, say the scientists.

    The researchers found that the tumors had lost these mutations by various means, including immune-mediated elimination of cancer cells containing these mutations, leaving behind cancer cells without the mutations, or by deleting large regions of their chromosomes in all cancer cells.

    “In some instances,” says Anagnostou, “we found that chromosomes in the cancer cells’ nuclei were missing an entire arm containing these mutated genes.”

    Between one and six of the eliminated neoantigens were shown to generate a specific immune cell response in each of the patients, researchers found.

    “Our findings offer evidence about how cancer cells evolve during immunotherapy,” Velculescu says. “When the cancer cells shed these mutations, they discard the evidence that would normally lead them to be recognized by the body’s protective immune cells.”

    See the full article here .

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    Johns Hopkins Campus

    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

     
  • richardmitnick 12:48 pm on January 8, 2017 Permalink | Reply
    Tags: A test that will detect all of the major cancer types, , Cancer, ,   

    From MIT Tech Review: “Liquid Biopsies Are About to Get a Billion Dollar Boost’ 

    MIT Technology Review
    M.I.T Technology Review

    January 6, 2017
    Michael Reilly

    A billion dollars sounds like a lot of money. But when your ambitions are as big as the cancer-detection startup Grail Bio’s are, it might not be enough.

    As CEO and ex-Googler Jeff Huber puts it, Grail’s aim is to create “a test that will detect all of the major cancer types.” Already the recipient of $100 million in funding from DNA sequencing company Illumina and a series of tech luminaries, Grail believes that adding another zero to its cash balance will put its lofty goals within reach. The company announced Thursday that it plans to raise $1 billion, has “indications of interest” from investors, and would move quickly to secure the hefty cash infusion.

    Whether Grail succeeds turns on the company’s ability to dramatically expand an emerging technology known as the liquid biopsy. It works by sequencing DNA from someone’s blood and looking for tell-tale fragments that indicate the presence of cancer. Dennis Lo, a doctor in Hong Kong, was among the first to show the technique’s promise. He’d previously used it to detect fetal DNA in a mother’s bloodstream. That led to a much safer form of screening for Down’s syndrome that is now in wide use.

    Lo has experimented with liquid biopsy as a way to catch liver and nasopharyngeal cancers, with some encouraging results. But he urged caution in assuming the technique could be translated to all cancers.

    Grail, which was spun out of Illumina about a year ago, has launched its first trials to see whether liquid biopsies can spot cancers earlier and more reliably than other screening tests.

    For his part, Huber seems to understand that he’s got a mountain to climb. After losing his wife to colorectal cancer, Grail’s mission is deeply personal. He acknowledges that detecting cancer DNA may be difficult, because the disease mutates rapidly as it advances, and varies immensely from one type to another. He says his company will rely on sequencing the DNA of tens of thousands of subjects to build a library of cancer DNA that computers can then decipher.

    Beyond the high-minded talk of turning the tide in the war against cancer, though, is a more cynical reading of the situation. As a unit within Illumina, Grail was an expensive, long-shot bet to create a new market for its gene sequencing machines. As a separate, now cash-rich company, Grail figures to become one of Illumina’s biggest customers. And venture capital will foot the bill, whether or not the experiment works.

    See the full article here .

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    The mission of MIT Technology Review is to equip its audiences with the intelligence to understand a world shaped by technology.

     
  • richardmitnick 11:20 am on January 5, 2017 Permalink | Reply
    Tags: , Cancer,   

    From RCINJ via PrincetonInfo: “C Is for ‘Cancer’ — But Also for ‘Cure’ “ 

    Rutgers University
    Rutgers University

    Rutgers Cancer Institute of New Jersey

    Rutgers Cancer Institute of New Jersey

    2

    PrincetonInfo.com

    [I do not like doing articles like this one; but they are part of the story.]

    THIS POST IS DEDICATED TO JBMT WHO FOUGHT LIKE HELL TO SAVE HER MOTHER’S LIFE.

    December 14, 2016
    Diccon Hyatt

    Ever since the first vaccines were created in the 1700s, doctors have been finding ways to force the body’s own immune system to fight disease. One of the more difficult targets for immunotherapy has been cancer, but recent advances in the field have turned immuno-oncology into one of the most promising frontiers in medicine.

    At last these treatments have made their way out of labs and into the hands of doctors and are now saving the lives of cancer patients. Immuno-oncology is also big business for pharmaceutical makers in the Route 1 corridor. Companies like Bristol-Myers Squibb and Advaxis are at the forefront of the field that has become one of the hottest sectors in biotech in the past several years. And at the Rutgers Cancer Institute of New Jersey, researchers are field testing the new arsenal in the war against cancer.

    Dr. Janice Mehnert is a medical oncologist in the melanoma and soft tissue oncology program and director of the Phase 1 investigation program at the Rutgers Cancer Institute of New Jersey. She has personally treated hundreds of patients using the latest immunotherapy drugs. In a recent trial she tested an antibody called Pembrolizumab, made by Merck and marketed as Keytruda, on a range of different types of cancer. She has seen results from the trials of Keytruda and other drugs that have made her use a word that is rarely, if ever, uttered by doctors who treat cancer.

    “When you treat advanced cancer, the word ‘cure’ is not used,” she says. “You are not used to seeing responses that last.” Like most oncologists, Mehnert doesn’t usually use the term “cure” because standard treatments suppress cancer without killing it off completely. Most of the time, the word “remission” is used after a successful cycle of chemotherapy. The cancer may be dormant, but cancer survivors know that the disease might still be there, waiting to come back. With immuno-oncology, Mehnert is cautiously using the C-word. “While not all patients respond, if you are one of those patients that does respond, it could last for a very long time. We’re maybe even thinking it’s a cure.”

    Keytruda has so far been approved by the FDA for certain kinds of melanoma, lung cancer, and head and neck cancer.

    The immune system regularly detects and destroys cancer cells. But in the case of cancerous tumors, the cells are able to disguise themselves from white blood cells and avoid attack. “When a tumor develops in your body, generally it’s because your immune system is asleep at the wheel,” Mehnert explains. “Some insult happens, and your immune surveillance goes off and your tumor is allowed to develop. It’s called immune tolerance,” she says. “The immune system becomes tolerant of the invader for some reason, and when that happens, sometimes tumors get flooded with tumor-fighting lymphocytes that are kept quiet and inactive. Immune therapy sort of wakes those lymphocytes up.”

    Immuno-oncology research has focused on determining exactly how the cancer cells make themselves invisible to lymphocytes and finding ways to defeat the chemical disguise.

    Keytruda targets the interaction of two proteins, PD-1 (programmed cell death) and PD-L1. These two proteins are what scientists call an “immune checkpoint” that stops white blood cells from attacking healthy tissue. By blocking this interaction, the Pembrolizumab allows the patient’s own cells to wipe out the tumors. When it works, it’s so effective that Mehnert flirts with the term “cure.” Furthermore, it seems to work for many different kinds of cancer.

    “It works with multiple different tumor types and multiple different diseases,” Mehnert says. “That’s one of the things that’s so exciting about the field. We’re seeing responses that are durable, without a tremendous amount of side effects, although there are side effects that are significant.”

    But the downside is that it only works for about 11 to 30 percent of patients. Part of Mehnert’s research is figuring out in advance which patients will respond to the antibody, and which won’t. The studies suggest so far that people who have high levels of the PD-L1 protein will do best with the treatment. But it’s not easy to measure.

    “That is a question that a lot of us are working on very diligently,” Mehnert says. “Some people think the mutations within a tumor may predict a patient’s response.” One hypothesis is that cancers that are the result of mutation, such as lung cancer caused by tobacco smoke and skin cancer caused by sun damage, are the most responsive to treatment. “But that’s not a perfect hypothesis yet,” Mehnert says. Another possibility is that patients with microsatellite instability are more prone to getting cancer, especially colorectal cancer, but that they might also respond better to immunotherapy.

    A third possibility is that patients whose tumors are virally driven may be responsive to immunotherapy treatments. But none of that has been proven, and much work lies ahead for Mehnert and the other doctors conducting clinical trials all around the world. “It may be a combination of all three,” Mehnert says. “It’s a huge undertaking to study this.”

    And that’s just Pembrolizumab. She is also running a trial of Talimogene, made by Amgen. Talimogene is actually a custom-made virus that is directly injected into tumors. Rutgers is studying the effects of this treatment combined with immunotherapy, and Mehnert says they are getting “interesting results” from the combination.

    They are also testing Pemrolizumab in combination with various other treatments including chemotherapy and other novel agents. Yet another drug targets IL-10, an anti-inflammatory receptor. “We have a spectacular menu to work with,” Mehnert says. “We’d love to get the word out about what we’re doing here.”

    The arsenal of immuno-oncology is growing rapidly, and several Route 1 companies are at the forefront. Bristol-Myers Squibb has led the field with Opdivo, which has been shown in clinical trials to extend the lives of patients with certain cancers including malignant melanoma. In November Opdivo was approved for the most common type of head and neck cancer. An earlier trial of Opdivo as a first line of defense against lung cancer proved no better than standard treatment, however. (Currently the drug is a second-line treatment, to be used after conventional therapy has failed.) In that trial the drug was tested on patients with relatively low levels of PD-1, the protein that is thought to be a key for the drug’s effectiveness.

    BMS is investing heavily in immuno-oncology for its future business. According to company reports, Immuno-oncology research makes up a large part of its $4 billion annual R&D budget. To follow up with Opdivo, the company has many anti-cancer products in the pipeline, each codenamed CheckMate.

    “We have a comprehensive clinical portfolio of investigational and approved immuno-oncology agents, many of which were discovered and developed by our scientists,” the company said in a recent statement. “We pioneered the research leading to the first regulatory approval for the combination of two immuno-oncology agents and continue to study the role of combinations in cancer.”

    Currently its three approved immunotherapy agents are Opdivo, Yerevoy, and Empliciti, delivered alone or in combination. BMS expects to have eight additional agents in clinical trials by the end of the year. The company says it is currently running 50 clinical trials for 20 tumor types.

    The company appears to be in something of an immuno-oncology arms race with rival Merck, whose Keytruda is the main competitor to Opdivo at the moment. Other top pharmaceutical companies AstraZeneca, Pfizer, and Roche all have immune-oncology drugs in the pipeline as well.

    Advaxis, based on College Road East, has three immuno-oncology agents under development. While the larger pharma companies are targeting the most common types of cancer, smaller companies like Advaxis are using their limited resources to pursue “orphan” markets where there is currently no effective treatment. Advaxis’ first agent is meant for late-stage recurrent cervical cancer caused by the HPV virus. It uses genetically modified bacteria that alert the immune system to the presence of a tumor, training it to develop anti-tumor antibodies in a process that is similar to what a vaccine does. (U.S. 1, September 11, 2013.)

    Advaxis is a good illustration of the potential of immunotherapy within the wider biotech sector. In 2013, according to the trade magazine Stat News, the company was almost out of money and unable to make payroll for its six employees. But new CEO Daniel J. O’Connor was able to successfully turn the company around thanks to a successful clinical trial of its anti-cervical cancer treatment and a deal with Amgen that brought in $70 million in cash and stock. In short, a risky bet on immunotherapy for cancer paid off.

    Looking at the picture worldwide, many companies are pouring billions into numerous new anti-cancer immunotherapies. Not all of them will work, and some will duplicate others’ efforts. But Mehnert and other scientists believe the end result could be a revolution in the way cancer is treated.

    “Whenever there’s a hot drug out there, most companies try to develop something similar — the ‘me too’ phenomenon,” Mehnert says. “But competition is not a bad thing. It’s not bad to have smaller biotechs come along and concentrate on a space no one thinks about.”

    It’s not just pharmaceutical companies making advancements, either. Long before anyone realized immunotherapy could be profitable, scientists in academic settings funded by public money were hard at work looking for ways to cure cancer. In fact, the history of immunotherapy goes back further than most people would think.

    In 1796 Edward Jenner invented the world’s first vaccine when he administered the relatively benign cowpox disease to healthy people as a way of preventing deadly smallpox. Further research over the centuries led to more vaccines that wiped out smallpox entirely and effectively combated polio, whooping cough, measles, and other once-common scourges.

    In the late 1980s Dr. Steven Rosenberg, working at the National Cancer Institute in Maryland, began using immune cells to treat patients who had melanoma. The techniques have become vastly more complex, but the basic idea is the same: activate the body’s natural defenses to destroy the invader.

    For Mehnert testing new immuno-oncology therapies is more than just a scientific endeavor. As a New Jersey native, she believes she is helping her own community. Mehnert grew up in Bradley Beach and now lives in Holmdel. She studied biology and English as an undergraduate at Rutgers and the University of Sussex in Britain. She went to medical school at UMDNJ-Robert Wood Johnson, completing a year of lab research at the National Institutes of Health.

    Growing up on the Jersey shore, where skin cancer from sun exposure was prevalent, had an effect on Mehnert’s career. Her mother was a teacher and her father worked for Federal Carbide. “I was incredibly close to my grandmother, who was ill a lot while I was a teenager,” Mehnert says. “I never understood anything that was going on, and that was a powerful motivating factor for when I went into medicine. I liked science; it was something I was good at and interested in. My uncle actually developed lung cancer when I was in medical school, and that was the key point where I knew I was going to go into oncology. He didn’t get into clinical trials.”

    Mehnert says many patients don’t have the information they need about clinical trials, which in some cases could be life saving.

    “It’s so important for patients to demand information about clinical trials. There are patients whose lives were saved for no other reason than they got into an immunotherapy study.”

    Mehnert says ideally, doctors would inform patients about clinical trials that they might be eligible for. Currently, however, it is up to patients to seek out clinical trials if conventional therapy doesn’t work for them. “Patients need to be educated,” Mehnert says.

    See the full article here .

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    About Rutgers Cancer Institute of New Jersey
    Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, the Cancer Institute of New Jersey is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention. Physician-scientists at Rutgers Cancer Institute engage in translational research, transforming their laboratory discoveries into clinical practice. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-8013 or visit http://www.cinj.org/giving. Follow us on Facebook at http://www.facebook.com/TheCINJ.

    The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. System Partner: Meridian Health (Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, Southern Ocean Medical Center, and Bayshore Community Hospital). Affiliate Hospitals: JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), and Robert Wood Johnson University Hospital Somerset.

    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 1:03 pm on January 3, 2017 Permalink | Reply
    Tags: Cancer, , , Metformin   

    From Harvard Medical: “Diabetes Drug vs. Cancer” 

    Harvard University
    Harvard University

    harvard-medical-school-bloc

    Harvard Medical School

    December 20, 2016
    SUE McGREEVEY

    1
    Image: Getty Images

    Considerable evidence has indicated that a drug used for more than 50 years to treat Type 2 diabetes can also prevent or slow the growth of certain cancers. But the mechanism behind metformin’s anticancer effects has been unknown.

    Now, a team of Harvard Medical School investigators at Massachusetts General Hospital has identified a pathway that appears to underlie metformin’s ability both to block the growth of human cancer cells and to extend the lifespan of the C. elegans roundworm. Their findings imply that this single genetic pathway plays an important role in a wide range of organisms.

    “We found that metformin reduces the traffic of molecules into and out of the nucleus—the ‘information center’ of the cell,” said Alexander Soukas, HMS assistant professor of medicine at Mass General and senior author of the study published in Cell.

    “Reduced nuclear traffic translates into the ability of the drug to block cancer growth and, remarkably, is also responsible for metformin’s ability to extend lifespan,” Soukas said. “By shedding new light on metformin’s health-promoting effects, these results offer new potential ways that we can think about treating cancer and increasing healthy aging.”

    Metformin appears to lower blood glucose in patients with Type 2 diabetes by reducing the liver’s ability to produce glucose for release into the bloodstream. Evidence has supported the belief that metformin blocks the activity of mitochondria, the powerhouses of the cell. But, Soukas said, more recent information suggests the mechanism is more complex.

    Several studies have shown that individuals taking metformin have a reduced risk of developing certain cancers and of dying from cancers that do develop. Current clinical trials are testing the impact of metformin on cancers of the breast, prostate and pancreas. Several research groups are working to identify its molecular targets.

    Soukas’ team had observed that, just as it blocks the growth of cancer cells, metformin slows growth in C. elegans, suggesting that the roundworm could serve as a model for investigating the drug’s effects on cancer.

    Their experiments found that metformin’s action against cancer relies on two elements of a single genetic pathway: the nuclear pore complex, which allows the passage of molecules into and out of the nucleus, and an enzyme called ACAD10. Basically, metformin’s suppression of mitochondrial activity reduces cellular energy, restricting the traffic of molecules through the nuclear pore. This shuts off an important cellular growth molecule called mTORC1, resulting in activation of ACAD10, which both slows the growth and extends the lifespan of C. elegans.

    In human melanoma and pancreatic cancer cells, the investigators confirmed that drugs in the metformin family induced ACAD10 expression, an effect that depended on the function of the nuclear pore complex. Without the complete signaling pathway—from mitochondrial suppression through nuclear pore restriction to ACAD10 expression—cancer cells were no longer sensitive to the effects of metformin-like drugs.

    “Amazingly, this pathway operates identically, whether in the worm or in human cancer cells,” said Soukas. “Our experiments showed two very important things: If we force the nuclear pore to remain open or if we permanently shut down ACAD10, metformin can no longer block the growth of cancer cells. That suggests that the nuclear pore and ACAD10 may be manipulated in specific circumstances to prevent or even treat certain cancers.”

    The essential contribution of ACAD10 to metformin’s anticancer action is intriguing, Soukas added, because the only published study on ACAD10 function tied a variant in the gene to the increased risk of Type 2 diabetes in Pima Indians, suggesting that ACAD10 also has a role in the drug’s antidiabetes action.

    “What ACAD10 does is a great mystery that we are greatly interested in solving,” he said. “Determining exactly how ACAD10 slows cell growth will provide additional insights into novel therapeutic targets for cancer and possibly ways to manipulate the pathway to promote healthy aging.”

    Support for this study includes National Institutes of Health grants R03DK098436, K08DK087941, R01DK072041 and R01CA166717; a Broad Institute SPARC Grant; and the Ellison Medical Foundation New Scholar in Aging Award.

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    harvard-medical-school-campus

    The Harvard Medical School community is dedicated to excellence and leadership in medicine, education, research and clinical care. To achieve our highest aspirations, and to ensure the success of all members of our community, we value and promote common ideals that center on collaboration and service, diversity, respect, integrity and accountability, lifelong learning, and wellness and balance. To be a citizen of this community means embracing a collegial spirit that fosters inclusion and promotes achievement.

    Harvard University campus

    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.

     
  • richardmitnick 2:40 pm on December 31, 2016 Permalink | Reply
    Tags: , Cancer, , Not good news, Some newer cancer drugs are no more life-saving than older treatments   

    From Discovery: “Study: Some newer cancer drugs are no more life-saving than older treatments” 

    HAVING JUST SUFFERED THE DEATH OF MY WIFE OF 53 YEARS FROM A COMBINATION OF THE DRUGS SHE WAS GIVEN FOR LUNG CANCER, I FIND THIS ARTICLE VERY DISHEARTENING. I RECENTY POSTED https://sciencesprings.wordpress.com/2016/12/04/from-nyt-immune-system-unleashed-by-cancer-therapies-can-attack-organs/ ABOUT IMMUNOTHERAPY DRUGS AND THEIR MIXED BLESSING, AND https://sciencesprings.wordpress.com/2016/12/05/from-technion-via-globes-research-chemotherapy-can-cause-metastasis/ ABOUT THE FACT THAT CHEMO CAN KILL AN ORIGINAL TUMOR BUT ACTUALLY HELP METASTASIS. SO, WHERE CAN WE TURN? PRAYER?

    Discovery News
    Discovery News

    Dec 30th 2016
    Ed Cara

    When it comes to cancer drugs, newer may not always mean better, according to a study published Thursday in the journal JAMA Oncology.

    Researchers took a look at over 50 drugs that had been approved to treat cancer between 2003 to 2013 by one or more health agencies in the U.S., England or Australia. Looking at data on risks and benefits after the drug was already on the market, they found a mixed results.

    Collectively, these 50 drugs did do better at extending patients’ lives and improving their quality of health than the drugs available in 2003, but there was a lot of variation. A third of new treatments failed to keep people alive any longer, and for at least one type of cancer — thyroid cancer — there were no new drugs at all that improved people’s survival rates. There was a worrying trend with risk too — even as half the new drugs provided improvements in people’s quality of life, a similar percentage were less safe than what came before. All told, one in every five new drugs failed to be either more life-saving, health-improving, or safer than earlier, generally cheaper drugs.

    Cancer is the nation’s second leading cause of death, and billions of dollars are invested in research and drug development every year. And this December, Congress passed the 21st Century Cures Act, which will spend part of a total $6.3 billion to fund cancer drug research and speed the FDA’s approval process.

    But whether that money will be effective is a bigger open question. Critics of the legislation, which include Vermont senator Bernie Sanders, have argued that the new reforms will only lower the standards of new drug approval, while doing little to reduce the high sticker price patients pay for new chemotherapy drugs.

    “Though further research is needed, our analysis may indicate that spending on new cancer drugs is not always commensurate with their clinical benefits,” the authors of the JAMA Oncology study wrote. “This may be reason for patients and clinicians to take pause when considering new treatments, particularly if related expenditures are of concern.”

    Digging deeper into their numbers, about 43% of new drugs were shown to extend someone’s life an average 3 months longer [STUPID CLAIM. WHAT IS THREE MONTHS?]or more, a milestone doctors consider a worthwhile clinical improvement [IDIOCY]. The top winners were breast cancer drugs, which provided an average eight or so extra months [SORRY, NOT IMPRESSED] of survival.

    But the researchers also noticed that the better-performing a drug appeared on paper, the less sturdy the evidence supporting these benefits was, and the less agreement different health agencies had about its track record. That suggests that at least in some cases, the authors wrote, we might still be overhyping how wondrous they really are [“MIGHT STILL BE”? NO QUESTION. JUST WATCH AN OPDIVO COMMERCIAL].

    See the full article here .

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  • richardmitnick 12:22 pm on December 29, 2016 Permalink | Reply
    Tags: , Cancer, CAR-T therapy, ,   

    From SA: “Experimental Cancer Therapy Makes Inroads Treating Brain Cancer” 

    Scientific American

    Scientific American

    December 29, 2016
    Meghana Keshavan

    The immunotherapy approach may soon be commercially available for leukemia and lymphoma.

    1
    Credit: Akira Ohgaki Flickr (CC BY 2.0)

    Glioblastoma is one of the deadliest cancers — an illness that responds to few treatment options, and often poorly. But a single case study that uses an experimental immunotherapy to treat these brain tumors might give oncologists a new way to approach the disease.

    The therapy, called CAR-T, is controversial and has faced hurdles in clinical trials. It has shown great promise in treating blood cancers like leukemia and lymphoma — but has proven challenging in treating other forms of the disease, including solid tumors.

    “This is the first example of CAR-T working in solid tumor cancers,” said Dr. Behnam Badie, chief of neurosurgery at City of Hope and a key investigator in the study. “In the initial treatments, I was holding my breath, waiting to get called in the middle of the night to go rescue somebody. But it’s amazing how safe it was.”

    The results are being published this week in the New England Journal of Medicine.

    Researchers at the City of Hope cancer treatment center in the Los Angeles Area tested a CAR-T therapy out on a 50-year-old man with recurrent multifocal glioblastoma — that is, several tumors growing in tandem in his brain. He had failed all other available treatments.

    CAR-T therapy involves extracting a patient’s immune cells, re-engineering them to learn how to target their cancer, and then feeding them back into the body. Surgeons removed the tumors, and then infused the experimental cellular therapy directly to the regions where the cancer had grown (other CAR-T treatment protocols are usually intravenous).

    The patient was in remission for about seven months after the CAR-T infusions began. The tumors did come back — but not in the areas that responded to the T cells, Badie said.

    This experimental therapy may soon be available commercially for certain blood cancers, as two drug makers — Novartis and Kite Pharma — are on the verge of filing for approval with the Food and Drug Administration.

    The glioblastoma therapy targets cells with the IL-13Rα2 antigen, a receptor which is found commonly on cells in brain tumors. City of Hope researchers are testing out a number of other antigens specific to brain cancers, Badie said, though they’re not disclosing which.

    Notably, the treatment was fairly innocuous, Badie said, which was certainly unexpected, since CAR-T therapy is notorious for its adverse events. In particular, Badie said he was bracing himself for neurotoxicity:

    “The results were really dramatic,” Badie said. “My own father passed from glioblastoma 10 years ago — and I never imagined we’d get to this stage so fast.”

    There have been other trials studying CAR-T’s efficacy in glioblastoma, but with intravenous application. The results from this one patient, Badie said, were good initial evidence that delivering CAR-T to the tumor site itself, rather than intravenously, might enhance efficacy. Badie said he believes that, based on this study, CAR-T could prove to be potent in other solid tumor cancers — particularly pediatric brain cancers.

    The results spurred both cautious optimism — and a dose of skepticism.

    “I can’t say this paper’s solved the problem of solid tumors, or this is the way to treat them,” said Dr. Jae Park, a hematologist-oncologist who specializes in CAR-T therapy at Memorial Sloan Kettering Cancer Center. “But it’s the first trial to show an objective response in glioblastoma, and suggests this is one way to get around the limitations of CAR-T.”

    But it’s a “flash in the pan,” according to Dr. Vinay Prasad, a hematologist-oncologist at the Oregon Health and Sciences University.

    “Even though this was a provocative case, even in this one case the cancer has already returned,” Prasad said in an email. “Will CAR-T work for other patients? Will it help most patients? Will it be better than alternatives? And will patients live longer or live better? We don’t know.”

    See the full article here .

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

     
  • richardmitnick 10:21 am on December 29, 2016 Permalink | Reply
    Tags: , Cancer, First CRISPR-Edited Cells Tested in Lung Cancer Patient, ,   

    From NOVA: “First CRISPR-Edited Cells Tested in Lung Cancer Patient” 

    PBS NOVA

    NOVA

    17 Nov 2016 [Where has this been hiding?]
    Tim De Chant

    1
    Geneticists edited the patient’s T-cells to more vigorously attack cancer cells. No image credit.

    In a first, oncologists and geneticists have edited a patient’s own immune cells using CRISPR and injected them as a treatment for an aggressive form of lung cancer.

    The trial, conducted at West China Hospital in Chengdu, is the first of what is expected to be many that will test the safety of using the gene editing technique to alter a person’s cells. U.S. trials are expected to begin in early 2017.

    Both studies will employ what are essentially advanced forms of immunotherapy, where doctors modify cells from a patient’s immune system to attack cancer cells. Because the cells involved are not a part of the reproductive system, their edited genomes cannot be passed on to any children the patients may have after the treatment.

    The patient involved in the Chinese study has been unsuccessfully treated for metastatic non-small-cell lung cancer, an aggressive form of the disease that’s often quickly fatal. The person received the first injection of CRISPR-edited cells on October 28.

    David Cyranoski, reporting for Nature News, has more details on the procedure:

    “The researchers removed immune cells from the recipient’s blood and then disabled a gene in them using CRISPR–Cas9, which combines a DNA-cutting enzyme with a molecular guide that can be programmed to tell the enzyme precisely where to cut. The disabled gene codes for the protein PD-1, which normally puts the brakes on a cell’s immune response: cancers take advantage of that function to proliferate.”

    The edited cells were then injected into the patient. Doctors hope the new cells will be able to exploit their PD-1 mutation to seek out and kill the cancer cells. It’s still too early to tell if the effort was safe or successful.

    If the patient shows no ill effects, the plan is to administer a second injection. Eventually, ten patients enrolled in the study will receive up to four injections.

    While scientists are optimistic about CRISPR’s broader potential in medicine, they’re less certain about whether this particular trial will be more effective than existing immunotherapies, which use modified proteins called antibodies that are easier to make in the lab than CRISPR-edited immune cells.

    See the full article here .

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

     
  • richardmitnick 4:46 am on December 29, 2016 Permalink | Reply
    Tags: Cancer, Friendship,   

    From The New Yorker: “My Friend Sam” 

    new-yorker-bloc-rea-irvin
    Rea Irvin

    The New Yorker

    [I hope that you have not been where I have been. I hope that you never go there. But if you have been there, you will know why I needed to cover this piece.]

    October 12, 2016 [Just found this.]
    Curtis Sittenfeld

    1
    Sam Park and the author in their college days.Courtesy Curtis Sittenfeld

    If you’re trying to tell the story of a friendship, do you start when the two of you met? For Sam and me, that was in the late summer of 1996, after we became co-editors of the arts and entertainment section of our university’s student newspaper.

    Do you start with the beginning of your friend’s life? Sam was born in 1976, in São Paulo, Brazil, the younger brother of two sisters, the son of parents who’d left Korea two years earlier and who, in 1991, would resettle in Torrance, California, just south of Los Angeles, and work as garment fusers.

    Do you start with your friend’s personality? Sam has always been loyal and generous, neurotic and melodramatic, wickedly but unostentatiously smart, frank and funny and someone who makes the people around him feel funny, too, because he laughs frequently and hard.

    Or do you start the story with the day everything changed? Which was in 2014, right around his thirty-eighth birthday, when Sam was given a diagnosis of Stage III-C stomach cancer. For the enviably uninitiated, about nine per cent of people who receive such a diagnosis are alive five years later.

    But to return to the middle: In college, Sam and I both had literary aspirations and tendencies to develop crushes on preppy guys who didn’t like us back. Pretty much from the start, however, we were crazy about each other. I suspect that if I were to look now at issues of the arts and entertainment section we edited, which was a Thursday insert, they’d make me blush, but we certainly enjoyed ourselves. One issue featured the “50 Most Beautiful Sexiest Men Alive of the Year at Stanford.” (Hey, we needed to get to those preppy, aloof guys somehow.) Another included a quasi-review in which, with unabashed undergraduate narcissism, we chronicled a “date” we’d gone on at a just-opened Mexican restaurant on campus.

    I was a year older than Sam, and the night before my graduation he sent one of the kindest e-mails of my life, all about how much he adored and believed in me. And really, though I had other close friends, there was something unique in Sam’s affection, a miraculous kind of blind spot: he always, unfailingly, thought that I was hilarious and wonderful, and that everything I wrote was brilliant. In the current age of social media, we all, of course, have the ability to publicly pretend we’re always hilarious and wonderful. But for someone to know the real you, the non-social-media you, the awkward and bad-jeans-wearing and years-away-from-publishing-novels you and still think you’re great, just as you are, is an extraordinary gift. And Sam’s inexplicably generous view of me never diminished. A few years ago, I attended a lecture at which the speaker recommended that people marry their biggest fan. Uh-oh, I thought. My biggest fan is Sam. When I expressed the sentiment to my husband, he laughed and said, “You should tell Sam that.”

    After college, Sam and I lived in different cities—he earned a Ph.D. in English in L.A., and then became a professor in Chicago; I moved around before settling in St. Louis. We saw each other every year or two, and I remember fragments from this decade-and-a-half stretch: the key chain that I gave him featuring a silver charm in the shape of a book, with “Pride and Prejudice” inscribed on the cover (yes, it was kind of cheesy, but Sam was a Jane Austen super-fan who, as an undergraduate, had written a play based on her most famous novel); the time we were at the beach, and I went swimming, and he didn’t remove his clothes, including his socks and wingtip oxford lace-up shoes. (If he swam, he told me later, “I think I was afraid of the fun I might have.”) In 1999, my younger sister and I had a long layover at LAX, and this was when a person without a ticket could still get through security; Sam met us as we deplaned and bestowed on me an enormous, impractical, beautiful bouquet of flowers.

    We read early drafts of each other’s work, and it was Sam who supplied me with the Korean dialogue used by one of the characters in my first novel, “Prep,” which came out in 2005; I blurbed his first novel, “Shakespeare’s Sonnets,” when it was published the following year. He stayed with me and my boyfriend (I’d finally snagged one) when a short film he’d written and directed was part of a festival in Philadelphia; when my boyfriend and I got married, at the drunken hotel gathering after the reception, Sam sat on the lap of my friend’s cute husband; and when my first child was born, Sam brought her a pink-and-white striped sweater. In other words, the years passed, we grew up, and I probably took a lot about our friendship for granted. And then, in April, 2014, I e-mailed Sam an article from the Times that I suggested could serve as inspiration for his next novel. He responded, “Curtis, I have cancer.”

    Sam returned to his parents’ condo in Torrance in order to receive treatment at U.C.L.A. Surgery removed ninety per cent of his stomach, which meant that in order to avoid losing a dangerous amount of weight—and Sam had always been thin—he was supposed to consume about six small meals throughout the day, in addition to taking digestive enzymes. But he often felt too sick to eat. He was chronically constipated, and the radiation and chemotherapy left him sometimes nauseous and often exhausted. Remarkably, he still pulled off the feat of writing the first draft of a novel during his recuperation. We texted often, but when I asked if I should come visit he told me to save the trip for if the cancer returned, because that’s when his prospects would really look bad.

    Sometimes we texted about Sam’s sickness, but often we discussed matters that were far more mundane (Did we identify more with Abbi or Ilana on “Broad City”?) or downright gossipy, like a huge advance that someone had just got for a novel, or the guy we’d known in college who’d married a woman and, according to Facebook, now appeared to be dating a man. I’d e-mail Sam sections of my novel-in-progress, which I truly felt like I was writing for him—it was a modern retelling of “Pride and Prejudice,” which is to say that it combined three of Sam’s favorite things: Jane Austen, Lizzy Bennet, and me.

    In January, 2015, Sam went back to Chicago, where he reported experiencing a new gratitude for his life—his students, his friends, the apartment he’d just moved into. When I completed my novel, which I’d decided to call “Eligible,” I sent it to my editor, my sisters, and a few other writers. Sam live-texted me as he read the final pages, and he was the very first person to finish it.

    “DON’T CHANGE A WORD,” he declared.

    Then: “who are you!!!??? who wrote this??!!!!!”

    Then: “motherhood has changed u. uve never written with such freedom joy and love of life its the most bighearted expansive novel you’ve ever written.”

    I texted back, “I’m dedicating the book to you.”

    To which Sam replied, “are you serious???!!! that almost makes it worth it for me to die of cancer.”

    Last November, I flew from St. Louis to Chicago to hand-deliver to Sam an advance copy of “Eligible,” and I’m not exaggerating when I say that being greeted by him at the airport was—sexual orientations be damned—the most romantic moment of my life. In our delight at seeing each other, our multiple hugs, we out-“Love Actually”–ed “Love Actually.” Then we took a taxi to a fancy restaurant high up in a downtown hotel, where we were meeting our friend Shauna for lunch.

    Though he was mostly still eating many small meals, Sam had kept his stomach empty in order to indulge at this one; we consumed expensive food, admired the view of Lake Michigan, and gossiped. After lunch, Shauna went home to her baby while Sam and I walked around in the cold and gossiped some more. A week later, Sam returned to his parents’ condo in Torrance for Thanksgiving, and almost immediately things started going wrong.

    “Spent Sunday in emergency room after having three hours of severe nausea,” he texted. Or, “Yesterday I had severe cramps that felt like I was being repeatedly stabbed in my stomach with a knife.”

    He eventually stopped eating solid food, relying instead on Boost brand “nutritional drinks” and an intravenous formula known as T.P.N. Every night, before bed, his sister would spend an hour hooking up his T.P.N. tubes. It took two months, plus multiple and often excruciating CT scans, ultrasounds, X-rays, and biopsies, to confirm that the cancer had returned.

    Sometimes, Sam was too tired, or in too much pain, to text. But, at other times, he was still game to kid around. Once, when I was texting him from a children’s holiday concert and he was at the hospital, he joked that there should be a Hallmark Hall of Fame movie about us, with a montage that cut between me at the concert and him in the operating room; we decided that, for maximum schmaltz, the carol accompanying the montage should be “Have Yourself a Merry Little Christmas.” He also regularly invoked “Terms of Endearment,” telling me I was Shirley MacLaine and he was Debra Winger.

    In February, he embarked on a course of palliative chemo. Around this time, he called with a particularly grim update about how he was doing. Then he light-heartedly added, “So anyway…” and wanted to discuss, in great detail, an embarrassing secret I’d recently divulged.

    I booked a ticket to visit for two weeks hence; this was the trip he’d once encouraged me to delay until things were really bad, but now he didn’t protest. Indeed, he sounded so terrible that I wondered if I should make the trip sooner.

    Flying out to L.A., I imagined that Sam and I might talk for five minutes, then I’d sit there and read while he slept. Instead, after not hugging hello because he was immuno-compromised, we astonished his family and ourselves with a marathon six-hour conversation. Sam and I talked about novels and other writers, about love and sex and marriage and friendship, about George W. Bush and adult coloring books and how the food Sam craved most was a greasy slice of Domino’s cheese pizza. We got our usually reticent friend Emily to text us a picture of her pregnant belly because it turns out that, when a person with metastatic cancer requests something, people tend to comply.

    Perhaps surprisingly, for most of the time, Sam and I laughed, and, about five hours in, we both cried. Sam expressed his willingness to visit me as a ghost after his death, which was an offer of unparalleled sweetness and also one I wasn’t sure I wanted to accept. I told him about a segment I’d heard on N.P.R. describing the parents of a little boy with terminal cancer who explained their son’s impending death to him by closing the curtain next to his hospital bed, staying on the other side of the curtain, and saying, “This is just like when you’re going to be dead. I’m still here, you’re still there. We just can’t see each other.”

    The next day, with characteristic self-consciousness, Sam and I texted to congratulate each other on how our visit had been like a great novel: It had contained comedy, pathos, a tearful climax, and a satisfying dénouement.

    As writers, Sam and I know that the expected way to conclude an essay about your friend who has awful cancer is with his death. But fulfilling expectations is often tedious, and Sam is not dead. In fact—marvelously, thrillingly—he’s now much better than he was when I saw him in January. He was, his doctor has since informed him, literally starving then. But it appears that the chemo is shrinking his tumor, because he can eat solid food again and was able to enjoy that slice of Domino’s cheese pizza he’d yearned for. In July, I returned to Los Angeles, and we ate at a restaurant that Sam, who knows I’m a frequent People magazine reader, had selected owing to its popularity with celebrities. He was more upset than I was that, when Al Pacino walked past our table, I saw him only from the back.

    Sam will continue the chemo for as long as it works, then he’s hoping to receive experimental immunotherapy treatment. To be sure, his days are circumscribed, and he spends a lot of time watching TV. But he can also go for walks and to restaurants, and he can take showers, all of which are things he couldn’t do a few months ago. His story is not finished.

    That day in Torrance, I asked Sam if he did or didn’t want me to write an essay about our friendship. “I’d love it,” he said. In the months since, he has texted me the following: “I want it to be a tearjerker.” And also: “I always planned on having you speak at my funeral so this is really killing two birds with one stone.”

    So here you go, Sam—once my co-editor, recently my Debra Winger, still my biggest fan, always and forever my beloved friend. Text when you have a chance and tell me what you think.

    Curtis Sittenfeld is the author of five novels, including “Eligible: A Modern Retelling of ‘Pride and Prejudice.’ ”

    See the full article here .

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  • richardmitnick 8:08 am on December 28, 2016 Permalink | Reply
    Tags: , At LANL Isotope research opens new possibilities for cancer treatment, Cancer,   

    From LANL: “Isotope research opens new possibilities for cancer treatment” 

    LANL bloc

    Los Alamos National Laboratory

    1
    Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources, to plasma physics and new materials. No image credit.

    August 17, 2016 [This just appeared in social media.]
    Nancy Ambrosiano
    Communications Office
    (505) 667-0471
    nwa@lanl.gov

    Computer models supporting spectroscopy unlock behavior of actinium-225

    A new study at Los Alamos National Laboratory and in collaboration with Stanford Synchrotron Radiation Lightsource greatly improves scientists’ understanding of the element actinium.

    SLAC SSRL Tunnel
    SLAC SSRL

    The insights could support innovation in creating new classes of anticancer drugs.

    “The short half-life of actinium-225 offers opportunity for new alpha-emitting drugs to treat cancer, although very little has been known about actinium because all of its isotopes are radioactive and have short half-lives,” said Maryline Ferrier, a Seaborg post-doctoral researcher on the Los Alamos team. “This makes it hard to handle large enough quantities of actinium to characterize its chemistry and bonding, which is critical for designing chelators.”

    The insights from this new study could provide the needed chemical information for researchers to develop ways to bind actinium so that it can be safely transported through the body to the tumor cell. “To build an appropriate biological delivery system for actinium, there is a clear need to better establish the chemical fundamentals for actinium,” Ferrier said. “Using only a few micrograms (approximately the weight of one grain of sand) we were able to study actinium-containing compounds at the Stanford Synchrotron Radiation Lightsource and at Los Alamos, and to study actinium in various environments to understand its behavior in solution.”

    Medical isotopes at Los Alamos

    Medical isotopes have long been a product of the Los Alamos specialty facilities, which create strontium-82, germanium-68 and other short-lived isotopes for medical scans. Taking advantage of the unique multidisciplinary capabilities of the Laboratory, researchers use the linear particle accelerator at the Los Alamos Neutron Science Center (LANSCE) to provide rare and important isotopes to the medical community across the United States. The expansion into actinium exploration moves the research forward toward treatment isotopes, as opposed to only diagnostic materials, says Ferrier.

    For the actinium work, a spectroscopic analysis called X-ray Absorption Fine Structure (XAFS) was used, a sensitive technique that can determine chemical information such as the number of atoms surrounding actinium, their type (i.e., oxygen or chlorine) and their distances from each other. To help understand actinium’s behavior in solution and interpret the data obtained with XAFS, these experimental results were compared with sophisticated computer model calculations using molecular-dynamics density functional theory (MD-DFT).

    The study showed that actinium, in solutions of concentrated hydrochloric acid, is surrounded by three atoms of chlorine and six atoms of water. Americium, another +3 actinide often used as a surrogate for actinium, is surrounded only by one chlorine atom and eight water molecules. It has been assumed in the past that actinium would behave similarly to americium.

    “Our study shows that the two are different in a way that could help change how actinium ligands are designed,” Ferrier said. “We’re actively working to gather more fundamental data that will help understand how actinium chemically behaves.”

    Actinium useful for targeted Alpha therapy

    Perhaps the most potent impact of these studies will be on the application of the isotope actinium-225, which is used in a novel, attractive cancer treatment technique called targeted alpha therapy (TAT). TAT exploits alpha emissions from radioisotopes to destroy malignant cells while minimizing the damage to healthy surrounding tissue. “Our determination that actinium’s behavior in solution is different than other nearby elements (such as americium) is directly relevant to TAT in a biological environment, which is always a complex solution,” said Ferrier.

    Actinium-225 has a relatively short half-life (10 days) and emits four powerful alpha particles as it decays to stable bismuth, which makes it a perfect candidate for TAT. However, TAT with actinium can only become a reliable cancer-treatment if actinium is securely bound to the targeting molecule, as the radioisotope is very toxic to healthy tissue if it is not brought quickly to the site of disease.

    Nature Communication Paper: Spectroscopic and Computational Investigation of Actinium Coordination Chemistry, by authors M. G. Ferrier, E. R. Batista, J. M. Berg, E. R. Birnbaum, J. N. Cross, J. W. Engle, H. S. La Pierre, S. A. Kozimor, J. S. Lezama-Pacheco, B. W. Stein, S. C. E. Stieber and J. J. Wilson.

    Funding: Support for portions of this research was provided by the Los Alamos LDRD program and the U.S. Department of Energy (DOE) Office of Science. Related work was supported by a postdoctoral fellowship from the Glenn T. Seaborg Institute and the Los Alamos National Laboratory’s Director’s postdoctoral fellowship. The Stanford Synchrotron Radiation Lightsource is a DOE Office of Science User Facility at the Department’s SLAC National Accelerator Laboratory.

    See the full article here .

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    Los Alamos National Laboratory’s mission is to solve national security challenges through scientific excellence.

    LANL campus
    Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is operated by Los Alamos National Security, LLC, a team composed of Bechtel National, the University of California, The Babcock & Wilcox Company, and URS for the Department of Energy’s National Nuclear Security Administration.

    Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

    Operated by Los Alamos National Security, LLC for the U.S. Dept. of Energy’s NNSA

    DOE Main

    NNSA

     
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