ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club

 
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ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
ROTTWEILER Update
 A NESTLÉ PURINA PUBLICATION DEDICATED TO ROTTWEILER ENTHUSIASTS   VOLUME 16 | SUMMER 2018

                                   OSTEOSARCOMA
                                     RESEARCH
                                      A New Vaccine & Gene Expression Profiling
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
SUMMER 2018

                ROTTWEILERS MAY BENEFIT FROM

     ADVANCES IN
OSTEOSARCOMA RESEARCH
                                “Benelli,” or “Benny” for short, was           panion Animal Hospital. Rottweiler
                                5 years old in 2007 when he was                owners since 1988, they adored the
                                diagnosed with osteosarcoma in                 intelligence and versatility of the
                                his right front leg. The gregarious            working breed. Benny, one of four
                                Rottweiler, titled in conformation,            male Rotties who shared their home,
                                obedience, carting, and as a therapy           had a special gift as a certified
                                dog, seemed to have a bum leg from             reading education assistance dog.
A tough, complicated            the start. At 18 months old, Benny,               “We wanted to know what was
                                painfully lame, had surgery for                going on with Benny’s leg,” says
cancer, no one knows            elbow dysplasia.                               Kelly Skiptunas. “Benny was
                                  When the lameness came back                  unbelievably smart and intuitive.
exactly what causes
                                three years later, owners Kelly and            Everyone loved him. He loved all
osteosarcoma, and efforts       Dr. Anthony Skiptunas of Wrightsville,         people, especially children.”
                                Pennsylvania, took Benny to be                    Initially diagnosed with severe
to better understand the        examined at Cornell University Com-            osteoarthritis in his leg and elbow,
                                                                               Benny, they learned a few months
cancer have been challenging.                                                  later, also had early-stage osteo-
                                                                               sarcoma, a tiny lesion invisible on a
                                                                               radiograph but apparent on a bone
                                                                               scan. Their options were dismal.
                                                                                  A tough, complicated cancer, no
                                                                               one knows exactly what causes
                                                                               osteosarcoma. Standard treatment
                                                                               for the aggressive, most common
                                                                               bone cancer in dogs is amputation
                                                                               of the affected leg followed by
                                                                               chemotherapy to help reduce the
                                                                               risk of metastasis. About 50 percent
                                                                               of dogs receiving the standard
                                                                               treatment survive nine to 11 months
                                                                               after diagnosis and surgery, about
                                                                               20 percent survive two years, and
                                                                               about 5 percent survive three years.
                                                                               When dogs are treated with ampu-
                                                                               tation alone, the median survival
                                Kelly Skiptunas and “Benny” (AM/CAN            is six to seven months. More than
                                CH Oakview’s Roughrider v Esmond RN,
                                CI, TT, CGC, RTD, TDI, R.E.A.D certified),     90 percent of dogs receiving no
                                wearing a brace on his front leg treated for   treatment or alternative holistic
                                osteosarcoma, receive the American Kennel
                                Club’s ACE (Award for Canine Excellence)
                                                                               treatments die from metastatic
                                Award for Pet Therapy in 2012.                 disease within three to five months.
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ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
ROTTWEILER Update

                                                                                     THINGS TO KNOW ABOUT
                                                                                     CANINE OSTEOSARCOMA

                                                                                     • It is the most common bone
                                                                                       cancer in dogs
                                                                                     • It can occur in any bone, but
                                                                                       the legs account for 75 to 85
                                                                                       percent of cases
                                                                                     • Virtually all dogs from large
A certified reading education assistance dog, Benny was adored by children because     and giant breeds, as well as
he listened attentively and patiently as they practiced reading aloud.                 large and giant mixed-breed
                                                                                       dogs, are at greater risk for
  Efforts to better understand               “We didn’t want to amputate               this disease
osteosarcoma have been challeng-           his leg, he was so young,” Kelly          • Signs include lameness, swelling
ing. Recent advances include a             Skiptunas says.                             at the tumor site and pain
new canine osteosarcoma vaccine              Post-surgical care involved Benny       • Irritability, aggression, loss of
developed at the University of             wearing an external fixator daily for       appetite, weight loss, whimpering,
Pennsylvania that shows promise in         two months. Every four hours, the           sleeplessness, and reluctance
extending survival following surgery       family adjusted the fixator to help         to exercise often relate to pain
and chemotherapy. At the University        stretch the bone so it would grow,        • Standard treatment involves
of Minnesota, investigators are using      and every night, Dr. Skiptunas              amputation of the affected leg
gene expression profiling to help          unwrapped the bandages and                  and chemotherapy
them understand the biological             carefully cleaned the surgical site
behavior of osteosarcoma tumors.           to reduce the risk of infection.          Source: The National Canine Cancer
Insights may help them learn how           Benny breezed through chemo-              Foundation
quickly the disease progresses locally,    therapy with no side effects and
how quickly it spreads to other sites,     continued his important job at
and what factors may accelerate            read-to-a-dog programs, where
or delay disease progression.              children gathered around him to
  Meanwhile, the surgery team at           take their turns reading aloud. He
Cornell evaluated Benny’s case, and        and Kelly Skiptunas also visited
determined he was an ideal can-            hospitals, rehabilitation centers
didate for a limb-sparing surgery          and assisted-living facilities.
known as longitudinal bone trans-            When he was 10 years old in 2012,
port. The procedure removes the            Benny became the first Rottweiler to
affected portion of the bone and           receive the American Kennel Club’s
then forms new bone, or a free             ACE (Award for Canine Excellence)
transport segment, via osteotomy,          Award for Pet Therapy honoring
eventually fusing the defective            his many contributions as a therapy
area with healthy bone.                    and reading education assistance
                                                                                                                           3
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
SUMMER 2018

                                           dog. It was a proud day when he          cells that remain in the body after
                                           and Kelly Skiptunas received the         standard of care treatment and
                                           honor at the AKC National Cham-          eliminate them, thus delaying or
                                           pionship. Three months later — five      preventing relapse.
                                           years after being diagnosed with           Listeria monocytogenes is a bac-
                                           osteosarcoma — Benny passed              terium that triggers a strong cellular
                                           away from another, unrelated can-        immune response. Although in people
                                           cer, hemangiosacoma.                     unmodified Listeria can cause a
                                                                                    serious and sometimes deadly infec-
                                           A PROMISING VACCINE                      tion when contaminated food is
                                             Greater understanding about how        ingested, the bacteria in this vaccine
                                           tumors and the immune system             has been genetically attenuated,
                                           interact have contributed to the         or weakened, so as not to cause
                                           development of a promising osteo-        infection or disease.
                                           sarcoma vaccine immunotherapy,             Explaining the rationale behind
“The Listeria vaccine                      says Nicola Mason, BVetMed, PhD,         the vaccine, Dr. Mason says, “most
essentially wakes us the                   DACVIM, associate professor of           dogs relapse with metastatic disease
                                           medicine and pathobiology at the         after chemotherapy, suggesting that
immune system and directs                  University of Pennsylvania.              not all cancer cells are eliminated
                                             A pilot study of 18 dogs treated       by chemotherapy. The Listeria
it to specifically eliminate               with a live recombinant, HER2-           vaccine essentially wakes up the
the remaining tumor cells                  expressing Listeria (ADXS31-164)         immune system and directs it to
                                           vaccine showed it doubled the            specifically eliminate remaining
by delivering a target tumor               survival rate compared to an his-        tumor cells by delivering a target
                                           torical control group. The dogs in       tumor molecule into the system.
molecule into the system.”                 the study had surgery to remove            “Immune cells that have been
                                           their primary tumor followed by          educated by the vaccine will then
Nicola Mason, BVetMed, PhD, DACVIM,
                                           four chemotherapy treatments,            seek out cells that express the target
associate professor of medicine and
pathobiology, University of Pennsylvania
                                           and then they received three doses       molecule and specifically kill them.
                                           of the vaccine every three weeks.        Essentially, we are aiming to gener-
                                           The median survival was 956 days         ate an effective anti-tumor immune
                                           compared to 423 days for the             response.”
                                           control group.                             A phase-two clinical trial, sponsored
                                             Funded by Advaxis Inc., a human        by Morris Animal Foundation, has
                                           biotechnology company, the phase-        begun at 11 university hospitals
                                           one study conducted at the Univer-       across the U.S. and Canada using
                                           sity of Pennsylvania included two        the ADXS31-164 vaccine. The study,
                                           Rottweilers. “One was a 7-year-old       performed through the Comparative
                                           male and the other was a 6 1/2-year-     Oncology Trials Consortium, aims
                                           old bitch,” says Dr. Mason. “Both had    to treat 80 dogs with the vaccine
                                           forelimb lesions and underwent           following standard of care amputa-
                                           amputation, follow-up chemotherapy       tion and chemotherapy and deter-
                                           and then received the vaccine. Both      mine whether these promising
                                           dogs did very well; the male lived       results are also seen in a larger
                                           956 days following the vaccine           group of dogs. The trial also aims
                                           treatment, and the female lived          to evaluate immune parameters
                                           886 days.”                               that might predict “responders”
                                             The vaccine uses a genetically         versus “non-responders.”
                                           modified Listeria to deliver a tumor-      Aratana Therapeutics, a company
                                           associated antigen to stimulate the      that markets innovative therapies
                                           immune system and activate cyto-         for dogs and cats, has received a
                                           toxic (killer) T cells. These killer T   conditional license for a lyophilized,
                                           cells specifically recognize cancer      or freeze-dried, version of this vaccine.
4
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
ROTTWEILER Update

The company hopes to receive full
licensure in the next year.              ROTTWEILERS WITH OSTEOSARCOMA MAY BE
   To be eligible to participate in      CANDIDATES FOR VIGOR TRIAL
the clinical trial, dogs cannot have
evidence of metastatic disease at        A novel oncolytic immunotherapy for treatment of canine osteosarcoma
the time of amputation surgery. If       is being investigated at the University of Minnesota. The study is
dogs develop metastatic disease          designed to learn more about how well a genetically modified vesicular
during their chemotherapy and            stomatitis virus (VSV) kills cancer cells.
before receiving the vaccine, owners       Dogs chosen for the study will receive either the VSV treatment or
have the option of fast-tracking         a placebo. Neither the owner nor the investigators will know which
their dog to receive the vaccine.        treatment the dogs are given. Owners and dogs will benefit because
   “About one-third of dogs develop      the participants will receive the best available standard of care for this
metastasis before their fourth           disease, including amputation of the affected leg and chemotherapy.
chemotherapy treatment,” says            Additionally, advanced imaging studies will allow veterinarians caring
Dr. Mason. “By including the fast-       for the dogs to determine disease progression at an earlier time when
track group in this study, we can        other treatment alternatives still can be considered.
determine whether this approach            To participate, owners must cover the cost of a screening appoint-
can delay the progression of grossly     ment and diagnostics to determine if their dog is a good candidate
evident metastatic disease.”             for the study. Once accepted, owners must be able to take their dogs
   In addition to improving the          for periodic recheck visits. The study covers up to $8,600 in care,
standard of care for dogs with           which includes the VSV treatment, surgery and part of the costs for
osteosarcoma, the long-term goal         chemotherapy.
of the University of Pennsylvania          To be eligible, dogs must:
researchers is to learn whether the      • Be diagnosed with osteosarcoma in a limb bone
same vaccine could be used to            • Weigh more than 44 pounds
help children with bone cancer. In       • Be healthy, with no significant health concerns
humans, the majority of osteosar-        • Be spayed or neutered
coma cases occur in children.            • Be current on vaccinations, flea and tick prevention, and heart-
   “Taking a comparative oncology          worm protection
approach, we believe that our canine     • Have no evidence of metastasis on a chest X-ray
patients may help to guide a pediatric   • Have had no previous treatment for their tumor
human clinical trial so we can learn       For information about participating in the study, please contact
whether this approach might benefit      Andrea Eckert, research study technician, at 612-625-3157 or
both species,” says Dr. Mason.           aleckert@umn.edu.

A POTENTIAL CANCER
DIAGNOSTIC TEST
  Cancer researchers at the Univer-
sity of Minnesota are working to
identify the molecular properties
of various tumor types, including
osteosarcoma, in an effort to gather
information that will help them
diagnose cancer risk and predict
disease behavior more accurately.
Their ultimate goal is to develop
effective strategies to treat and
eventually prevent osteosarcoma
in both dogs and children.
  A recent University of Minnesota
osteosarcoma study, published in
the January 2018 issue of Cancer
Research, reported on evaluating
                                                                                                                      5
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
SUMMER 2018

                                       the transcriptional profile of           five-year survival for osteosarcoma
                                       osteosarcoma tumors in dogs,             is around 80 percent, and the 10-
                                       humans and mice.1 Also known             year survival is 50 to 60 percent.
                                       as gene expression profiling, a             “One of our goals has been to
                                       transcriptional profile quantifies       define peculiar genetic traits that
                                       the abundance of messenger RNA           may contribute to osteosarcoma
                                       (mRNA) molecules for every gene          in dogs and whether any of these
                                       in cells or tissues.                     traits may also contribute to this
                                          RNA, which is short for ribonucleic   disease in people,” Dr. Modiano
                                       acid, acts as a messenger in cells,      explains. “Our present goal is to
                                       transcribing genetic information         understand how specific mutations
                                       from DNA into amino-acid sequences       help tumors mold their environment
                                       that become the protein products         and evade the immune system.
                                       of gene expression. The differential     Identifying such mutations, in dogs
“While the GCESS method                patterns of gene expression in           or humans, will help us develop tools
                                       tumors from individual patients          to diagnose the disease earlier when
was developed using                    allow researchers to categorize          interventions are more likely to
osteosarcoma as a model,               cancers, such as osteosarcoma, into      produce long-term benefits and to
                                       subgroups with different behaviors       design effective strategies that are
we found it is widely                  and different prognoses.                 better tailored to each individual
                                          The comparative medicine approach     patient.”
applicable to virtually any            used by the University of Minnesota         The researchers used next-gen-
                                       researchers, gleaning information        eration sequencing to analyze all
type of tumor where
                                       from dogs, mice and humans,              of the mRNA in human, dog and
genome-wide sequencing                 provides opportunities to better         mouse tumors. “Our hypothesis
                                       understand osteosarcoma. The             was that despite the highly com-
information can be obtained.”          study team was made up of sci-           plex karyotypes (chromosomal
                                       entists with diverse backgrounds,        variation) seen in osteosarcoma,
Jaime Modiano, VMD, PhD, the Perlman
                                       including bioinformatics, genetics       transcriptional profiles would allow
Endowed Chair of animal oncology,
                                       and genomics, pathology, immu-           us to categorize this cancer into
University of Minnesota
                                       nology, molecular biology, cancer        distinctive, clinically relevant sub-
                                       biology, and stem-cell biology.          types,” says Dr. Modiano.
                                          One of the study investigators,          Samples from newly diagnosed
                                       Jaime Modiano, VMD, PhD, the             human and dog osteosarcoma
                                       Perlman Endowed Chair of animal          patients that had not yet received
                                       oncology at the University of            any therapy were included in the
                                       Minnesota, says, “Human, dog and         study. The dogs’ samples came from
                                       mouse osteosarcoma tumors share          a large number of breeds, includ-
                                       certain clinical and molecular simi-     ing many Rottweilers and Golden
                                       larities, but they also have import-     Retrievers, obtained between 1999
                                       ant species-specific differences.        and 2012.
                                       Insights gained from each species           The most exciting development
                                       help us improve our overall under-       from the study was the creation of
                                       standing of the disease.”                the gene cluster expression sum-
                                          A rare cancer in people, with         mary score (GCESS) methodology
                                       400 to 600 new cases diagnosed           to categorize tumors. The GCESS
                                       annually in the U.S., osteosarcoma       captures information from many
                                       is much more common in dogs. The         genes that are turned on and off
                                       small number of human tumors             coordinately, likely by the same
                                       available for study compounds the        mechanisms, says Dr. Modiano.
                                       ability of researchers to study the         “Because of the sheer size of the
                                       rare but deadly cancer. In children,     clusters and their tight correlation,
                                       adolescents and young adults, the        the GCESS method is significantly
6
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
ROTTWEILER Update

more powerful to achieve
this classification than bio-
markers that use a single
or even a few genes or mol-
ecules,” he says. “While the
GCESS method was devel-
oped using osteosarcoma as
a model, we found it is widely
applicable to virtually any
type of tumor where genome-
wide sequencing information
can be obtained.”
  Using the GCESS method,
the research team identified
three clusters that were
conserved across all three
species and that had clinical
significance in at least one
species. One cluster, discov-
ered by the team as part of
an earlier study, was strongly
associated with genes that
control cell division and DNA
repair. The investigators
confirmed their previous
observation that the relative
expression of this cluster
was highly predictive for
overall survival in dogs with
                                 A conformation champion, Benny also was active in obedience, carting, and working as a
osteosarcoma independent therapy dog.
of treatment.
  The other two clusters were            Skiptunas says, “The surgery                 LOOKING TO REPRINT?
indicative of immune cells being         doubled his life span. Now, looking
present within the tumor. “Inter-        back at what we went through, I              Rottweiler Update articles may
estingly, the relative abundance         don’t know if we could do it again.          be reprinted provided the article
of immune-cell transcripts was a         I am so thankful for the extra years         is used in its entirety and in a
strong predictor for outcome in          we had with him. He was special              positive manner. To request
human patients, but not in dogs with     to us and to so many other people            permission to reprint an article,
osteosarcoma,” says Dr. Modiano.         through his gentle, unassuming               please contact the editor at:
“The reasons for this are unclear,       nature as a therapy dog.” n                  barbara.fawver@purina.nestle.
but they provide a stark illustration                                                 com. Reprints should include the
of species differences that must be 1 Scott MC, Temiz NA, Sarver AE, et al.           following attribution: Used with
considered when dogs are used as Comparative Transcriptome Analysis                   permission from the Rottweiler
                                         Quantifies Immune-Cell Transcript Levels,
models for human cancer causation Metastatic Progression and Survival in              Update, Nestlé Purina PetCare.
or cancer treatments. Most impor-        Osteosarcoma. Cancer Research. 2018;
tantly, these differences do not         78(2):326-337.

negate the utility of comparative
approaches. To the contrary, under-
standing these differences makes it        Purina thanks Roberta Kelley-
possible to design better experiments      Martin, president of the Rott-
and to obtain more robust answers.”        weiler Health Foundation, for
                                           helping us to identify this topic
   Reflecting on her experience
                                           for the Rottweiler Update.
with Benny’s osteosarcoma, Kelly
                                                                                                                        7
ROTTWEILERUpdate - OSTEOSARCOMA RESEARCH A New Vaccine & Gene Expression Profiling - Purina Pro Club
SUMMER 2018

  RECORD YEAR FOR NATIONAL SPECIALTIES AT PURINA FARMS

  A record 38 National Specialties will be held this year at Purina Farms.
  The versatility of the Best in Class show and trial venue combined with
  its prime location in the middle of the country appeal to parent clubs,
  with many returning year after year. Custom-built for the dog fancy,
  the Purina Event Center offers a spacious indoor exhibition space
  complete with a separate benching and grooming area, dog bathing
  room, conference rooms, banquet rooms, Checkerboard Café, and
  numerous other amenities. The 346-acre property includes facili-
  ties for herding, tracking, coursing, diving dog, earthdog, and many
  more activities. Purina Farms is in Gray Summit, Missouri, about one
  hour from St. Louis.

    LEARN MORE

PURINA PRO PLAN INTRODUCES SAVOR WITH PROBIOTICS FOR DOGS
Purina Pro Plan is introducing SAVOR formulas for       small dogs, as well as calcium, phosphorus and
puppies and adult dogs made with guaranteed live        other minerals to help maintain strong teeth and bones.
probiotics to support digestive                                             Vitamin A and linoleic acid, an
health. SAVOR Shredded Blend                                                omega-6 fatty acid, nourish healthy
Chicken & Rice Puppy Formula,                                               skin and coat.
made with chicken as the No. 1                                                The large-breed formula contains
ingredient, contains DHA from                                               high-quality protein, including chicken
omega-rich fish oil to help nourish                                         as the No. 1 ingredient, plus EPA and
brain and vision development and is                                         glucosamine to help support joint
rich in antioxidants to help support                                        health and mobility. Optimal protein
a puppy’s developing immune                                                 and fat levels help maintain lean
system. The complete and                                                         muscle and ideal weight and
                                     LEARN MORE                LEARN MORE
balanced puppy food also has                                                     body condition.
calcium, phosphorus and other                                     Both of these adult formulas also have a natural
                                               LEARN MORE
minerals to help build strong teeth and bones.                  prebiotic fiber, sourced from wheat bran, to
  The adult dog foods now with probiotics are: SAVOR help support digestive health. Purina Pro Plan Shredded
Shredded Blend Small Breed Chicken & Rice Formula Blend formulas feature a crunchy kibble combined with
and SAVOR Shredded Blend Large Breed. This small- tender, shredded pieces for delicious taste and texture.
breed food is high in protein, including chicken as the   Look for probiotics coming to other SAVOR formulas
No. 1 ingredient, to meet the needs of highly active    later this year.

DEADLINE IS JULY 31 FOR PRO CLUB MEMBERS TO SUBMIT WEIGHT CIRCLES
Don’t miss the cutoff of July 31, 2018, for mailing in    uploaded correctly. You can start
weight circles. After this date, weight circles will no   submitting receipts now, though
longer be accepted, as Purina Pro Club is introducing     once you submit receipts, you will
a new receipt submission program that will allow you      not be able to mail in any more weight circles. To get
to get your Purina Points into your account faster        started, click on the link below that will take you to
by taking a picture of your receipt from purchases        helpful tools — instructions and a video — and then
of eligible Purina dog food on your smartphone or         log on to your Pro Club account, register and begin
scanning the receipt into your computer and sub-          submitting receipts.
mitting it online. Your Purina Points will show up in
                                                           GO TO HELPFUL TOOLS
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