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Found 5 results

  1. Morris Animal Foundation answers questions about hemangiosarcoma May 21, 2020 "This is a webinar which answers some questions about hemangiosarcoma, a cancer dreaded by all golden retriever owners and veterinarians. Dr. Kelly Diehl, Morris Animal Foundation Senior Director of Science and Communications, speaks with Dr. Rod Page, Director of the Flint Animal Cancer Center, and Principal Investigator for the Foundation's Golden Retriever Lifetime Study." The presenter, Dr. Rodney Page, references insurance data from Scandinavia/other evidence that the incidence of this disease may be lower in EU/Nordic than in the US... brings up specifically potential for connection of spay neuter/ hormonal status of dogs as having a possible impact in that spaying and neutering of dogs is less in Nordic countries... further monitoring of the GR population in the Lifetime Study will lead to greater understanding. Agria Insurance - Breed Profile for Golden Retrievers Golden Retriever: 2006-2011 2011-2016 Additional Information... Two Decades of Advances in Canine Hemangiosarcoma. The Light at the End of the Tunnel is getting Brighter, and it’s not a Train! Jaime Modiano, VMD, PhD holds the Alvin and June Perlman Endowed Chair of Animal Oncology and is the Director of the Animal Cancer Care and Research Program of the College of Veterinary Medicine and the Masonic Cancer Center at the U of Minnesota. It is now believed that Hemangiosarcoma (HSA) is a cancer that arises from cells related to bone marrow nurse cells that support the formation of blood cells and blood vessels. HSA can occur in any breed, but some breeds are more prone to it than others. The disease is indistinguishable between breeds. Treatments that block the signals that cause disorganized growth and invasion of cells is limited once the cells have organized into malignant tissue. Early identification of the disease is critical in developing possible treatments. Research he is doing at U of Minn has developed a blood test which is used for early identification of the disease, and they are now doing a clinical trial to receive the experimental drug, eBAT, to determine the drug's potential to prevent progression of disease. For more information see: https://vetmed.umn.edu/centers-programs/clinical-investigation-center/current-clinical-trials/early-detection-target-hemangiosarcoma-cells-dogs-shine-project Propranolol and Hemangiosarcoma: Can We Use an Old Drug to Learn New Tricks? Erin Dickerson, PhD Associate Professor at the College of Veterinary Medicine and the Masonic Cancer Center Beta blockers are commonly used to treat hypertension, heart failure, arrhythmias, and anxiety. A correlation has been found between reduced cancer progression, metastasis and mortality and the use of beta blockers in cancer patients: breast, colon, prostate, pancreas, and ovarian cancers. Increased progression free survival and overall survival has been seen in melanoma and angiosarcoma patients. Infantile hemangioma is a common benign tumor of infancy in humans. It can grow quickly during the first year of life, but in most cases the masses slowly regress from a benign angiogenic mass to fibrofatty tissue. It is potentially disfiguring or life-threatening in about 10% to 15% of all cases. In 2008 systemic administration of propranolol was found to improve the treatment of infantile hemangioma. The treatment consists of topical timolol or oral propranolol (2mg/kg/day, TID). Children are often treated for 6-10 months, and the treatment is well-tolerated. There are about 300 cases of angiosarcoma each year. It is associated with toxins that damage DNA, such as vinyl chloride, thorium dioxide, and radiation. The primary sites are usually the liver, skin, and subcutaneous soft tissue. The progression free survival for advanced cases is about 4-6 months, and the 5 year survival is about 30-35%. Propranolol has been found to kill angiosarcoma cells, and to inhibit its growth. Using propranolol, the progression free survival moved from about 6 months to 11 months, and overall survival went from about 10-11 months to about 16-18 months. A prospective analysis of metastatic angiosarcoma patients lead to a median progression free survival of 9 months and an overall survival of 36 months. Regression of primary cardiac angiosarcoma and metastatic nodules were seen following propranolol as a single agent treatment. Based on the clinical effectiveness of propranolol against angiosarcomas, the EU gave propranolol an Orphan Drug Designation. Canine hemangiosarcoma is similar to that of human angiosarcoma. It’s a common cancer in dogs, and is typically found in the spleen, heart, or skin. Response to conventional treatments is poor with a median survival of about 4-6 months. Using a targeted bispecific toxin (eBAT) 6 month survival went from under 40% to about 70%. Propranolol acts as a cytostatic agent, it stops the growth of the cells without killing them. It prevents cancers from growing and spreading. When doxorubicin is used to treat hemangiosarcoma, a population of those cells are resistant to the doxorubicin. Propranolol alters the intracellular distribution of doxorubicin and increases the sensitivity of hemangiosarcoma cells to chemotherapy. Propranolol also blocks the ability of the tumor cells to take up nutrients from the tumor microenvironment, further limiting access to vital metabolites needed for tumor growth. When combined with the chemotherapy drug, doxorubicin, propranolol enhances the effects of the chemotherapy agent by increasing drug concentrations within tumor cells. The results from these studies are guiding the translation of propranolol into clinical practice and informing future studies with other beta blocker and chemotherapy combinations. A clinical trial opened July 1, 2019 to determine the tolerability and clinical benefit of propranolol combined with doxorubicin, the estimated 6 month disease free survival, and to determine if there is a correlation between propranolol concentration and treatment effect. Twenty dogs are being enrolled, with recruitment at U of Minnesota, U of Pennsylvania, and Purdue. CURRENT AKC Canine Health Foundation GRANTS 02534: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma Study information & Enrollment...PRO-DOX Propranolol and doxorubicin for dogs with splenic hemangiosarcoma https://vetmed.umn.edu/centers-programs/clinical-investigation-center/current-clinical-trials/pro-dox-propranolol-and-doxorubicin-dogs-splenic-hemangiosarcoma 02234-MOU (Co-investigator): A Novel Approach for Prevention of Canine Hemangiosarcoma
  2. A recent article provided by the Golden Retriever Club of America, Golden Retriever Health and Genetics Highlight: Neuronal Ceroid Lipofuscinosis in Golden Retrievers, by Ann Hubbs and Ron Rubrecht,, discussed the challenges faced in Fall 2018, by a breeder who had unsuspectingly bred a litter of puppies from two carriers of neuronal ceroid lipofuscinosis (NCL 5) – a devastating neurological disease considered rare in the breed. While a DNA test existed, most Golden Retriever owners wouldn’t be aware of the condition, let alone testing options. The breeder did the absolute right thing when realizing there was a problem, by working swiftly to genetically test their dogs, contacting owners, and working with the Breed Club to make other breeders aware of the risks of NCL 5. The situation for this breeder could arise for various conditions in many breeds. Inherited diseases that are generally rare in a breed are unlikely to be considered in selection by breeders. It could be that a genetic test isn’t available, or that it is not a priority for testing compared to more common inherited risks, or, increasingly, it might be a well-known condition in a breed in one country, but less known internationally. This is understandable, especially considering that the risks of an inherited disease in the breed as a whole, is not necessarily reflective of the risks for the breeding population. (Fig 1.) The dogs who are left intact and used in breeding, particularly by Show/Field breeders, is only a tiny percentage of the dogs making up the whole breed. It is easy to imagine how a few popular dogs who happen to be genetic carriers [See 'carrier' defined in glossary for AR inheritance] for a rare disease like NCL 5, could shift the risks of inheritance within a few generations without anyone realizing that there is a problem at all. For NCL 5 in the Golden Retrievers, fortunately, there is a genetic test available that can identify those dogs who are clear, carrier, or genetically affected for the condition. This will be especially valuable for those specific breeding lines within which the disease has occurred or is suspected. However, it is important to put into perspective how concerning NCL 5 is for the breed, relative to other important factors, in order to be sure that breeding decisions are made sensibly across all the considerations when making breeding plans. Currently, within a US population tested by Embark, only <1% of the dogs tested are carriers of the NCL 5 mutation. This is known as carrier frequency. At this level of carrier frequency, breeders can develop breeding plans that include clear and carrier tested dogs, to efficiently breed away from the mutation risk, without causing a genetic bottleneck or producing genetically affected puppies. It is important for a disease like NCL, which is still likely to be clinically rare in the breed, to breed away steadily to balance any other inherited risks, as well as allowing selection for positive characteristics. Avoiding a knee-jerk reaction will help to ensure that future generations have a greater variety of breeding lines to choose from. IPFD is continuing to develop plans for the Health Strategies Database for Dogs that aims to catalog all conditions that are being addressed by those designing breed-specific health programs around the world, especially kennel and breed clubs. See “Get a GRIHP on Breed Health” - Breed Health Strategies Presentation given by Brenda Bonnett at the 4th International Dog Health Workshop. What’s a GRIHP? Globally Relevant Integrated Health Profile... https://dogwellnet.com/files/file/422-4th-idhw-breed-specific-health-strategies-dogwellnet-resources-brenda-bonnett/ Additional information HGTD has a number of resources to help breeders and owners make informed decisions on genetic testing. You can search for genetic test providers, breed-specific diseases, and more information on tests/diseases HERE. Recently, HGTD has launched relevancy ratings for many of the tests that the participating genetic test providers are offering. Using data and information from researchers, test providers, kennel and breed clubs, and veterinary scientists, relevancy ratings are a way of indicating all of the currently known research material on a specific test for a specific breed. Additional information University of Missouri - Golden NCL: http://www.caninegeneticdiseases.net/GoldenNCL/ The Orthopedic Foundation for Animals records the NCL5 test results for Goldens - search at https://www.ofa.org/diseases/breed-statistics. Also see further information on Neuronal Ceroid Lipofuscinosis at OFA: https://www.ofa.org/diseases/dna-tested-diseases/neuronal-ceroid-lipofuscinosis. Research The NCL 5 mutation origin paper: Melville, SA., Wilson, CL., Chiang, CS., Studdert, VP., Lingaas, F., Wilton, AN. : A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics 86:287-94, 2005. Pubmed reference: 16033706. DOI: 10.1016/j.ygeno.2005.06.005. 2019 Villani, N.A., Bullock, G., Michaels, J.R., Yamato, O., O'Brien, D.P., Mhlanga-Mutangadura, T., Johnson, G.S., Katz, M.L. : A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Mol Genet Metab 127:107-115, 2019. Pubmed reference: 31101435. DOI: 10.1016/j.ymgme.2019.04.003. 2017 Katz, M.L., Rustad, E., Robinson, G.O., Whiting, R.E.H., Student, J.T., Coates, J.R., Narfstrom, K. : Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis :, 2017. Pubmed reference: 28860089. DOI: 10.1016/j.nbd.2017.08.017. 2016 Kolicheski, A., Johnson, G.S., O'Brien, D.P., Mhlanga-Mutangadura, T., Gilliam, D., Guo, J., Anderson-Sieg, T.D., Schnabel, R.D., Taylor, J.F., Lebowitz, A., Swanson, B., Hicks, D., Niman, Z.E., Wininger, F.A., Carpentier, M.C., Katz, M.L. : Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. J Vet Intern Med :, 2016. Pubmed reference: 27203721. DOI: 10.1111/jvim.13971. Mizukami, K., Yabuki, A., Kohyama, M., Kushida, K., Rahman, M.M., Uddin, M.M., Sawa, M., Yamato, O. : Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. Vet J 214:21-3, 2016. Pubmed reference: 27387721. DOI: 10.1016/j.tvjl.2016.05.004. 2015 Gilliam, D., Kolicheski, A., Johnson, G.S., Mhlanga-Mutangadura, T., Taylor, J.F., Schnabel, R.D., Katz, M.L. : Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab 115:101-9, 2015. Pubmed reference: 25934231. DOI: 10.1016/j.ymgme.2015.04.001. 2013 Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. : Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009. 2012 Mizukami, K., Kawamichi, T., Koie, H., Tamura, S., Matsunaga, S., Imamoto, S., Saito, M., Hasegawa, D., Matsuki, N., Tamahara, S., Sato, S., Yabuki, A., Chang, H.S., Yamato, O. : Neuronal ceroid lipofuscinosis in Border Collie dogs in Japan: clinical and molecular epidemiological study (2000-2011). ScientificWorldJournal 2012:383174, 2012. Pubmed reference: 22919312. DOI: 10.1100/2012/383174. 2011 Mizukami, K., Chang, H.S., Yabuki, A., Kawamichi, T., Kawahara, N., Hayashi, D., Hossain, M.A., Rahman, M.M., Uddin, M.M., Yamato, O. : Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan. J Vet Diagn Invest 23:1131-9,
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