• Parallels in human, dog oral tumors coul

    From ScienceDaily@1:317/3 to All on Mon Nov 29 21:30:32 2021
    Parallels in human, dog oral tumors could speed new therapies

    Date:
    November 29, 2021
    Source:
    Cornell University
    Summary:
    Recent research compared the genetic expression profiles of a
    nonlethal canine tumor and the rare, devastating human oral tumor
    it resembles, laying the groundwork for potential translational
    medicine down the road.



    FULL STORY ========================================================================== Recent Cornell research compared the genetic expression profiles of a
    nonlethal canine tumor and the rare, devastating human oral tumor it
    resembles, laying the groundwork for potential translational medicine
    down the road.


    ========================================================================== While canine acanthomatous ameloblastoma (CAA) is common and nonlethal, it
    has a strong resemblance to an oral tumor in humans known as ameloblastoma (AM).

    As a boarded veterinary dentist and oral surgeon, Dr. Santiago Peralta, associate professor at the College of Veterinary Medicine (CVM) and first author of the recent study in Scientific Reports, sees CAA in his clinic
    all the time.

    "This research was a good example of a full cycle of translational
    research," Peralta said. "We took something we were dealing with
    in the clinical setting, studied it in the bench setting and are now
    hoping to use it to help veterinary patients and, potentially, humans."
    The resemblance between CAA and AM had long been noted by scientists
    and clinicians, but no one had confirmed any molecular similarities. A
    previous study on AM tumors revealed the underlying mutations, piquing
    the interest of Peralta and his CVM colleagues. "We wondered if we should
    look at these mutations and see if they precipitate the canine tumor,"
    Peralta said.

    They did just that, publishing a study in Veterinary and Comparative
    Oncology in 2019, that revealed that both AM and CAA shared mutations
    in a well-known signaling pathway, known as the RAS-RAF-MAPK pathway.

    In their most recent study, Peralta and his colleagues analyzed a large
    genomic dataset generated by the Cornell Transcriptional Regulation
    and Expression Facility (TREx) to better understand the biological
    consequences of these mutations. While doing so, they compared the CAA
    tumors with another common canine tumor (oral squamous cell carcinoma)
    and healthy gum tissue. These samples were stored and made available
    through the Cornell Veterinary Biobank and gene expression was profiled
    with RNA sequencing by Dr. Jen Grenier and her team at TREx.

    The team also used genomic data from human tissues to run comparisons,
    thanks to their collaboration with a human oral cancer expert at the
    University of Turku in Finland. Through analyzing these different
    tissues, Peralta and his team were able to see that the mutations they
    had identified in their earlier study were largely responsible for the
    tumors they were seeing.

    They also found that CAA and AM are very similar at a molecular level, reinforcing the notion that dogs represent a potentially useful natural
    model of the human tumor. "All the dysregulated molecules and pathways
    in CAA tumor tissues were consistent with the mutations we'd found and remarkably similar to those observed in AM," he said.

    Now that they've connected the dots between the underlying mutations and dysregulated molecular pathways driving tumor formation, Peralta and his colleagues have been working to establish in vitro and in vivo models of different canine oral tumors that can be used to test potential drugs. Any drugs that might prove effective in treating oral tumors in dogs could
    also be promising candidates for human patients with analogue disease.

    "If dogs truly represent a useful clinical model of the disease, they
    also represent an immense opportunity," Peralta said. Because the CAA
    tumors are much more common in dogs than AM are in humans, scientists can rapidly enroll many more dogs in clinical trials and get more translatable
    data from those trials.

    Furthermore, dogs, which live in same type of environments as humans,
    are more accurate models of disease than other animal models. "My goal
    as a veterinarian is to bring solutions back to the clinic. We're not
    there yet, but we've made a major step toward that," Peralta said.

    ========================================================================== Story Source: Materials provided by Cornell_University. Original written
    by Lauren Cahoon Roberts. Note: Content may be edited for style and
    length.


    ========================================================================== Journal Reference:
    1. Santiago Peralta, Gerald E. Duhamel, William P. Katt, Kristiina
    Heikinheimo, Andrew D. Miller, Faraz Ahmed, Angela
    L. McCleary-Wheeler, Jennifer K. Grenier. Comparative
    transcriptional profiling of canine acanthomatous ameloblastoma
    and homology with human ameloblastoma.

    Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-97430-0 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2021/11/211129122821.htm

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