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judy mikowits

Discussion in 'XMRV Research and Replication Studies' started by consuegra, Sep 25, 2009.

  1. consuegra

    consuegra Senior Member

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    Experimental Pathology Seminar Series
    Judy Mikovits, PhD

    Research Director

    Whittemore Peterson Institute

    "Detection and Immune correlates of Infectious XMRV in the blood of
    patients with Neuroimmune Disease and Cancer."

    I think this is November 6th.

    Chris
     
  2. Cort

    Cort Phoenix Rising Founder

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    Raleigh, NC
    Interesting! The Reno subset!. Is this being held in Reno? At the Univ of Nevada, Reno (I think it is?. I wonder if its open to the public? Any links?
     
  3. consuegra

    consuegra Senior Member

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    judy mikovits

    It looks like Judy Mikovits is talking at the University of Utah on Nov 6.

    At the UK conference she said that the WPI had submitted research on a novel virus previously not associated with CFS to Science Magazine. I presume this will come out soon, probably in mid-October with the new issue. I cannot imagine that she will make a presentation until it is published.

    Chris
     
  4. acer2000

    acer2000 Senior Member

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    Do we know who was included in this study? Is this the original incline village cohort that they have followed all these years?
     
  5. Daisymay

    Daisymay Senior Member

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    judy mikovits

    Here is a link mentioning a special issue of the journal "Cytokine" where there will be abstracts and reviews from talks given by the various researchers at this international conference in Lisbon in October, with Dr Mikovits being one of them at 2.30-3.00pm on the 19th of October and the title of her talk is below:

    http://tinyurl.com/yd9e7mu

    "Detection and Immune Correlates of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"


    "Volume 48, Issues 1-2, Pages 1-160 (October-November 2009)
    Special Issue - Abstracts and Reviews: Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Research, Cellular and Cytokine Interactions in Health and Disease, Lisbon, Portugal, 18-21 October 2009"

    And on this link to the conference, presumably earlier link, if you go down to 2.30 Monday you'll see her name again but it says:

    http://www.trisociety2009.org/pdf/ScientificProgram.pdf
    "Late breaking plenary:Title embargoed until meeting per publication
    requirements."

    So I guess there is a full paper to be published somewhere, possibly Science, before the 19th Oct and this will be her speaking on these findings at this conference.

    I tried googling this MXRV virus and came up with the following, it sound squite heavy stuff but of course we don't know what the implications are for ME, have to wait and see.

    BW,

    daisymay
    .........................................................................
    These links are ordered in the time of publishing, earliest first. The research that came out at the beginning of September this year, the third article, seemed to get a very large amount of media coverage, there are pages of links on goggle telling the same story:

    http://www.rxpgnews.com/article_3865.shtml

    Virology

    New human retrovirus - Xenotropic MuLV-related virus (XMRV)
    By Howard Hughes Medical Institute
    Apr 1, 2006, 19:27

    Howard Hughes Medical Institute researchers and their colleagues have discovered a new retrovirus in humans that is closely related to a cancer-causing virus found in mice. Their findings describe the first documented cases of human infection with a retrovirus that is native to rodents.

    The researchers discovered the virus in patients with a rare type of prostate cancer. The patients in the study have a genetic mutation that compromised some of their natural defenses against viral infection. Thus, the researchers said their discovery raises the possibility that increased susceptibility to viral infection may play a role in development of some cancers. However, they emphasized that their findings by no means implicate the virus, dubbed XMRV, in causing prostate cancer. The virus may well have flourished as a result of the failure of the defense mechanism; and other factors such as chronic inflammation may play a more direct role in the cancer.

    The discovery of the new virus was made by an interdisciplinary research team led by Robert Silverman of Cleveland Clinic and HHMI investigators Joseph DeRisi and Don Ganem, both at the University of California at San Francisco. A paper describing the findings was published on March 31, 2006, in the journal, Public Library of Science Pathogens.

    The search for the new virus began when Silverman and his colleagues provided samples of a rare familial prostate cancer in which the viral-defense gene, RNASEL, had been mutated in a specific way. This mutation compromised the function of the enzyme produced by RNASEL, which normally shreds viral genetic material. Infected cells carrying the shredded viral genetic material are usually targeted for destruction by the immune system. While some scientists believe that such vulnerability to viral infection is connected to prostate cancer in these rare cases, others have presented evidence contesting that theory.

    To screen for viruses in the prostate tissue samples, DeRisi and Ganem used the Virochip, which was invented by DeRisi and his colleagues. The Virochip consists of a microarray of some 20,000 characteristic gene sequences -- called oligonucleotides -- representing a vast array of known viruses. The oligonucleotides are deposited as tiny spots on a small glass chip.

    To detect viruses from tissue samples, the researchers isolated genetic material from each sample and tagged the genetic material with a fluorescent tracer. They then applied the fluorescently tagged genetic material to the microarray chip. Since genes tended to adhere to those with a complementary genetic sequence, any viral gene sequences in the sample would attach themselves to corresponding viral sequences on the chip. The telltale fluorescence on spots on the chip signaled the presence of viral genetic material in the sample.

    Although the Virochip contains only sequences from known viruses, DeRisi said it can also detect new viruses because they invariably contain sequences that have been conserved in their evolution from related viruses.

    The initial screen of the RNASEL-mutant prostate cancers revealed the presence of a genetic sequence that closely resembled that of a mouse virus called murine leukemia virus (MuLV). Murine leukemia virus is known as an endogenous virus because it normally exists as an integrated part of the mouse genome, rather than as independent, infective particle. MuLV is also a retrovirus, meaning its genetic material is in the form of RNA. The RNA is then reverse transcribed into DNA that is integrated into the DNA of the host cell the virus is infecting.

    When the researchers isolated and sequenced the genome of the virus, they found that it was a xenotropic virus – one that can only grow in foreign cells other than mouse cells. Thus, they named the virus, Xenotropic MuLV-related virus, or XMRV.

    "This finding was a big surprise because most of these endogenous viral genomes have undergone such mutation and deletion that they are incapable of giving rise to viruses any more," said Ganem. "And while some of these viruses had been induced to grow in human cells in culture, the major question is whether such infection could ever happen in nature.

    "So, one of the things that is important about our study from a virologic point of view, is that this is the first really solid example of an authentic xenotropic retroviral infection in a human being," said Ganem.

    According to DeRisi, the Virochip made it possible to analyze these samples without preconceived biases about what viruses might be present. "Since the chip represents every known virus in one assay, it is agnostic as to what might be found," he said. "We would never have looked for this class of virus if it wasn't for the virus chip."

    Importantly, the researchers found that prostate cancers in which both copies of the RNASEL gene were crippled by mutation showed much more frequent XMRV infection than did those cancers that still had one normal copy of the RNASEL gene.

    "This link between the virus and RNASEL is the second finding that is important and is firmly established in this study," noted Ganem. "We don't see the infection in people who don't have the RNASEL mutation, which suggests strongly RNASEL is an important part of the defense against retroviral infection. This is the first evidence in humans of findings that were previously made only in vitro."

    DeRisi pointed out that detailed comparison of samples of the virus between people found that – although all were XMRV – they showed tiny genetic variations. "So, while it is the same virus in each patient, the viruses are different enough to say that they are most likely independently acquired and are not the result of some contamination of the samples," he said.

    Ganem cautioned that any link between XMRV and prostate cancer is tenuous at best. "First, the genetic variant we studied occurs in familial clusters that constitute only a very small sliver of prostate cancers," he said. "And secondly, there are many reasons to believe that the virus might not relate to prostate cancer."

    For example, he pointed out, analysis of prostate tissue by Silverman and his colleagues indicated that the virus appears only in a small percentage of connective tissue cells, called stromal cells, rather than in the tumors themselves. "So, one interpretation could be that the infection is entirely incidental to prostate cancer," said Ganem. "The patients with RNASEL mutations may be more likely to get the infection or perhaps less likely to clear it. Clearly XMRV is not a classic oncogenic virus."

    Nevertheless, said Ganem, an indirect link to cancer cannot be ruled out, since "in cancer research these days, there is a lot of interest in the stroma as the soil in which cancer arises." He added that the chronic inflammation from infection of stromal tissues may play a role in triggering such cancers.

    DeRisi observed that "it may be that men who are so-called RNASEL-mutant are just more susceptible to viruses in general, and this susceptibility has little to do with their cancer. Nevertheless, the fact that this virus is found in tumor tissue and that it is a new virus and the first of its kind ever documented in humans is an intriguing finding that demands to be followed up. This initial finding raises many questions. For example, what is the route of transmission? How is the virus passed from person to person? And are people the natural reservoir of this virus, or is it some other organism?"

    DeRisi and Ganem said they are planning studies to explore whether XMRV is restricted to prostate cancers or whether it is more widespread in the body and in other segments of the human population. To answer such questions, the researchers are developing a blood test that can be used in epidemiological studies.

    ...........................................................................

    http://www.lerner.ccf.org/news/notations/2007/1/2.php

    February 2007
    A Viral Link to Prostate Cancer

    XMRV, a recently discovered virus, is infectious and viral DNA was found in two patients with prostate cancer, according to a study recently published in the Proceedings of the National Academy of Sciences (PNAS).

    The findings establish XMRV as a new human retrovirus, a type of virus that has ribonucleic acid (RNA) as its genetic makeup. Upon entering a host cell, retroviruses, such as XMRV, produce viral DNA that inserts into the host's DNA, prompting the formation of more, identical viruses.

    These results are significant in that they validate that XMRV has infected humans, says Robert Silverman, Ph.D., Cancer Biology, who led the study. Future studies will determine whether XMRV is a contributing factor to the development of prostate cancer. If it is, the presence of XMRV could be an early indicator for prostate cancer and a possible therapeutic target.

    Collaborating investigators included Eric A. Klein, M.D., Cleveland Clinic's Glickman Urologic Institute, and Samson Chow, Ph.D., University of California at Los Angeles .

    The research also recently was awarded a $100,000 2006 Prostate Cancer Foundation Competitive Award. Only 63 proposals submitted by 423 investigators from 184 institutions in 23 countries were selected.

    Cleveland Clinic researchers and collaborators from the University of California at San Francisco first reported the identification of XMRV in prostate cancer in February 2006. However, until now, it was undetermined whether XMRV was an infectious virus. In this new study, XMRV generated from a patient's RNA was shown to infect human prostate cancer cells in the lab resulting in the production of new virus particles. The presence of XMRV in two prostate cancer patients was confirmed by determining the precise locations in the human genome where the virus DNA inserted itself.

    The research team discovered how XMRV enters cells through a cell surface protein that serves as the virus docking site. In their work, the team also developed a method of suppressing XMRV using an interferon, a protein produced naturally by human cells. Interferons help regulate the body's immune system, boosting activity when a threat, such as a virus, is present.

    ................................................................

    http://www.unews.utah.edu/p/?r=090809-13

    A Viral Cause of Prostate Cancer?

    RESEARCHERS FIND FIRST EVIDENCE OF VIRUS IN MALIGNANT PROSTATE CELLS

    September 7, 2009 -- In a finding with potentially major implications for identifying a viral cause of prostate cancer, researchers at the University of Utah and Columbia University medical schools have reported that a type of virus known to cause leukemia and sarcomas in animals has been found for the first time in malignant human prostate cancer cells.

    If further investigation proves the virus, XMRV (Xenotropic murine leukemia virus-related virus), causes prostate cancer in people, it would open opportunities for developing diagnostic tests, vaccines, and therapies for treating the cancer, according to the study published Sept. 7 online in the Proceedings of the National Academy of Sciences. Prostate cancer is expected to strike nearly 200,000 U.S. males this year, making it the second most common form of cancer, outside of skin cancers, among men.

    "We found that XMRV was present in 27 percent of prostate cancers we examined and that it was associated with more aggressive tumors," said Ila R. Singh, M.D., Ph.D., associate professor of pathology at University of Utah and the study's senior author. "We still don't know that this virus causes cancer in people, but that is an important question we're going to investigate."

    Singh, also a member of the U of U's Huntsman Cancer Institute and associate medical director at ARUP Laboratories, moved to Utah from Columbia University Medical Center in 2008, where she began this research. She remains an adjunct faculty member at Columbia.

    Along with providing the first proof that XMRV is present in malignant cells, the study also confirmed that XMRV is a gammaretrovirus, a simple retrovirus first isolated from prostate cancers in 2006 by researchers at the University of California, San Francisco (UCSF), and the Cleveland Clinic. Gammaretroviruses are known to cause cancer in animals, but have not been shown to do so in humans. The UCSF study did not examine benign (non-malignant) prostate tissues, so could not link XMRV to prostate cancer. They also did not find the virus in malignant cells.

    Singh and her fellow researchers examined more than 200 human prostate cancers, and compared them to more than 100 non-cancerous prostate tissues. They found 27 percent of the cancers contained XMRV, compared to only 6 percent of the benign tissues. The viral proteins were found almost exclusively in malignant prostatic cells, suggesting that XMRV infection may be directly linked to the formation of tumors.

    Retroviruses insert a DNA copy of their genome into the chromosomes of the cells they infect. Such an insertion sometimes occurs adjacent to a gene that regulates cell growth, disrupting normal cell growth, resulting in more rapid proliferation of such a cell, which eventually develops into a cancer. This mechanism of carcinogenesis is followed by gammaretroviruses in general. Singh is currently examining if a similar mechanism might be involved with XMRV and prostate cancer.

    In another important finding of the study, Singh and her colleagues also showed that susceptibility to XMRV infection is not enhanced by a genetic mutation, as was previously reported. If XMRV were caused by the mutation, only the 10 percent of the population who carry the mutated gene would be at risk for infection with virus. But Singh found no connection between XMRV and the mutation, meaning the risk for infection may extend to the population at large.

    While the study answers important questions about XMRV, it also raises a number of other questions, such as whether the virus infects women, is sexually transmitted, how prevalent it is in the general population, and whether it causes cancers in tissues other than the prostate.

    "We have many questions right now," Singh said, "and we believe this merits further investigation."

    Viruses have been shown to cause cancer of the cervix, connective tissues (sarcomas), immune system (lymphoma), and other organs. If the retrovirus is shown to cause prostate cancer, this could have important implications for preventing viral transmission and for developing vaccines to prevent XMRV infection in people.

    ....................................................................
     
  6. hvs

    hvs Senior Member

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    Wow, very interesting. Could this be the driver for the Incline subset? Could it even be the very root so that genetic predisposition (or changed genetic expression) + this bug = neuro-immune dysregulation = infections with very common viruses like EBV, HHV-6, etc.?
     

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