Innovative VETERINARY CARE
VOLUME 13 ISSUE 3
WHAT GENETICS TELLS US ABOUT LONGEVITY
CONTROLLING DIET, ENVIRONMENT, AND STRESS CAN POSITIVELY IMPACT A DOG OR CAT’S GENES AND LENGTHEN THEIR LIFESPAN. — P. 8
HOW VETERINARY DIAGNOSTICS HAVE ADVANCED IN 50 YEARS
TAKING A TCVM APPROACH TO FELINE COLITIS
SUMMER 2023
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Veterinary diagnostics, along with disease management and treatment options, have come a long way since the 1970s. — P. 12
By identifying the patterns of disharmony leading to feline colitis, the TCVM practitioner can treat the problem and bring the cat’s body back into balance. —P. 48
CHRONIC DIARRHEA IN DOGS — WHY AN INTEGRATIVE APPROACH HELPS
WAYS TO SUPPORT THE EQUINE MICROBIOME
An integrative treatment plan that encompasses the interconnected factors contributing to this challenging problem can lead to successful outcomes. — P. 18
EPIGENETICS AND CANINE CANCER — WHAT'S THE LINK?
Understanding the epigenetic changes associated with cancer in dogs provides insights into underlying disease mechanisms and identifies new treatment targets. — P. 26
Why providing forage diversity while minimizing stress will help balance a horse’s microbiome. — P. 54
CREATE A SUSTAINABLE MARKETING STRATEGY FOR YOUR PRACTICE
For optimal success, you need to be a marketer as well as a veterinary professional – here’s what to do. — P. 40
contents FEATURES
LONGEVITY IN 8 INDUCING COMPANION ANIMALS: WHAT GENETICS TELLS US
A SUSTAINABLE MARKETING STRATEGY FOR YOUR 40 CREATING VETERINARY PRACTICE
By Melissa L. Magnuson, DVM
By Megan Kelly, BVSC, CCRP
The genetics of companion animals are affected by diet, environment, and stress. By controlling these three aspects, we care for our patients’ genes and extend their longevity.
As a veterinary professional, you also need to be a marketer — and learn how to measure your marketing efforts for optimal success.
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HOW VETERINARY DIAGNOSTICS HAVE ADVANCED OVER THE LAST 50 YEARS
By Margo Roman, DVM, CVA, COT, CPT, FAAO
Thanks to a range of scientific and clinical advancements, veterinary diagnostics, along with disease management and treatment options, have come a long way since the 1970s.
Used with ozone therapy and other modalities, MBRT led to full recovery for an injured dog with an antibioticresistant urinary tract infection and damage to his autonomic nerves.
By Ron Carsten, DVM, PHD, CVA, CCRT Optimal support for dogs with chronic diarrhea relies on an integrative treatment plan that encompasses the interrelated factors contributing to this challenging health problem.
CLOSER LOOK AT THE LINK 26 ABETWEEN EPIGENETICS AND CANINE CANCER
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By Chris Bessent, DVM, MSOM, DIPL. OM, LAC By identifying the patterns of disharmony leading to feline colitis, the TCVM practitioner can use several modalities to treat the problem and bring the cat’s body back into balance.
INFLUENCING THE EQUINE MICROBIOME — AND 54 FACTORS HOW TO SUPPORT IT By Suus Bettink, DVM
Understanding the epigenetic changes that occur in canine cancer can provide insights into the underlying mechanisms of the disease, and help identify new targets for treatment.
High stress levels and a lack of forage diversity are among the factors causing imbalances in the equine microbiome.
By Lisa Miller, DVM, CCRT, CVA
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APPROACH TO 48 TCVM FELINE COLITIS
By Kelly Diehl, DVM, MS
THERAPY FOR 32 PBM MUSCULOSKELETAL DISORDERS IN COMPANION ANIMALS
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AUTONOMIC NERVES
By W. Jean Dodds, DVM
INTEGRATIVE APPROACH TO 18 AN CHRONIC DIARRHEA IN DOGS
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HELPS DOG RECOVER 44 MBRT FROM ANTIBIOTIC-RESISTANT INFECTION AND DAMAGED
OA and other musculoskeletal disorders are common in companion animals. Laser or PBM therapy is an alternative treatment option of choice for these patients.
PROFESSIONALS 59 VETERINARY ARE VULNERABLE TO STRESS — 7 WAYS TO EASE THE ANGST By Omer Rashid, DVM Stress is a serious problem among veterinarians. Recognizing the signs and using these calming techniques will help you control your stress before it becomes overwhelming.
advisory board Dr. Richard Palmquist, DVM GDipVCHM(CIVT) CVCHM (IVAS), graduated from Colorado State University in 1983. He is chief of integrative health services at Centinela Animal Hospital in Inglewood, California, former president and research chair of the AHVMA, and an international speaker in integrative veterinary medicine. Dr. Palmquist is a consultant for the Veterinary Information Network (VIN) and a past president of the AHVM Foundation. He has published two books, one for conventional veterinarians and a second for clients discussing how integrative thinking works.
48 COLUMNS & DEPARTMENTS
7 Editorial 30 Industry Innovations 39 From the AVH
Michelle J. Rivera, MT, VDT, is an instructor at the University of Wisconsin and The Healing Oasis Wellness Center, a post-graduate educational institution offering state-approved programs. She is coowner of The Healing Oasis Veterinary Hospital, offering massage, rehabilitation, chiropractic and Chinese and Western Herbology. Michelle completed the Chinese Herbal Medicine program from the China Beijing International Acupuncture Training Center, and is certified in Chinese Medicine by the Wisconsin Institute of Chinese Herbology.
Dr. Joyce Harman, DVM, MRCVS, graduated in 1984 from Virginia Maryland Regional College of Veterinary Medicine. Her practice is 100% holistic, using acupuncture, chiropractic, herbal medicine and homeopathy to treat horses to enhance performance and those with a variety of chronic conditions, with an emphasis on Lyme Disease. Her publications include the Pain Free Back and Saddle Fit Books, and numerous articles in lay and professional magazines. She maintains an informative website: www.harmanyequine.com.
43 From the AHVMA 51 From the VMAA 53 From the VBMA IN THE NEWS:
58 New Endocrine Guidelines from AAHA 62 How Updated State Laws Could
Change Virtual Veterinary Care
Dr. Steve Marsden, DVM, ND, MSOM, Lac. Dipl.CH, CVA, AHG lectures for IVAS, the AHVMA, the AVMA, and numerous other organizations. He is co-founder of the College of Integrative Veterinary Therapies and is a director emeritus of the National University of Natural Medicine in Portland OR. He authored the Manual of Natural Veterinary Medicine (Mosby); and Essential Guide to Chinese Herbal Formulas (CIVT). Dr. Marsden is extensively trained in alternative medicine, including Chinese herbology, acupuncture and naturopathic medicine. He has holistic veterinary and naturopathic medical practices in Edmonton, Alberta. In 2010, Dr. Marsden was named Teacher of the Year by the AHVMA; and Small Animal Veterinarian of the year by the CVMA in 2009. Dr. Jean Dodds, DVM, received her veterinary degree in 1964 from the Ontario Veterinary College. In 1986, she moved to Southern California to establish Hemopet, the first non-profit national blood bank program for animals. Dr. Dodds has been a member of many national and international committees on hematology, animal models of human disease, veterinary medicine, and laboratory animal science. She received the Holistic Veterinarian of the Year Award from the AHVMA in 1994.
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Dr. Barbara Fougere, DVM, CVAA graduated in 1986, and was named the American Holistic Veterinary Medical Association Educator for 2011. Dr. Fougere is the principal and one of the founders of the College of Integrative Veterinary Therapies. She has continued studying over the last 26 years, and has three Bachelor degrees, two Masters degrees, three post Graduate Diplomas, several Certifications and numerous other courses under her belt.
Dr. Christina Chambreau, DVM, CVH, graduated from the University of Georgia Veterinary College in 1980. She is a founder of the Academy of Veterinary Homeopathy, was on the faculty of the National Center for Homeopathy Summer School and has been the holistic modality adjunct faculty liaison for the Maryland Veterinary Technician Program and is the former Associate Editor of IVC Journal. Dr. Chambreau teaches classes in homeopathy for animals, lectures on many topics, speaks on Radio and TV, and is the author of the Healthy Animal’s Journal among other titles. She is now on the faculty of the Holistic Actions Academy, which empowers members to keep their animals healthy with weekly live webinars.
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A CLOSER LOOK AT THE LINK BETWEEN EPIGENETICS AND CANINE CANCER BY KELLY DIEHL, DVM, MS
Understanding the epigenetic changes that occur in canine cancer can provide insights into the underlying mechanisms of the disease, and help identify new targets for treatment.
Cancer is a complex disease, and despite decades of research, it remains a leading cause of death in dogs over two years old. We know cancer is not a monolithic disease, and that its development is influenced by many external factors, such as genetics and the environment. Mounting evidence suggests that epigenetics also plays a role in cancer development and progression. In this article, we’ll take a closer look at what we know about the relationship between canine cancer and epigenetics.
WHAT IS EPIGENETICS? Epigenetics studies the changes in gene expression that occur without altering the DNA sequence. This is important to remember, and is different from, for example, a mutation that alters DNA sequence (such as a deletion or frame shift). A variety of environmental factors, such as diet, exercise, stress, and exposure to toxins, can alter gene expression. Epigenetic changes also can be inherited from one generation to the next. Epigenetic changes can affect gene expression by altering the structure of DNA, modifying histones (proteins that help package DNA into chromatin), and altering the expression of non-coding RNAs (more on this later).
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Before we go much further, we probably need a quick refresher on DNA structure and basic molecular biology, in order to understand epigenetics.
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F irst, we need to remember something called the central dogma of molecular biology: DNA contains the information to code all the proteins in the body, and RNA is the messenger that transmits this information to the ribosomes responsible for making proteins.
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e must also precisely define what we mean by gene W expression. This term refers to the process involved in turning the DNA code contained in a particular unit identified as a gene into a “product” — typically a protein but also RNA.
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e should recall from basic biology class that two W processes — transcription and translation — are involved in gene expression. Transcription refers to the conversion of DNA code to RNA, and translation is the process occurring in the ribosomes where the information coded by the RNA is used to direct the formation of new proteins.
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astly, it’s important to remember that gene expression L is regulated — it doesn’t just “happen.” Factors that can affect gene expression include cellular signals, feedback mechanisms, and the environment.
WHAT DOES EPIGENETICS HAVE TO DO WITH CANCER? In cancer cells, epigenetic changes can alter the expression of genes that regulate cell growth and division, leading to uncontrolled cell growth and the formation of tumors. Epigenetic changes can also affect the ability of cancer cells to invade surrounding tissues and spread to other parts of the body. One of the most well-studied epigenetic changes in cancer is DNA methylation. As the name implies, DNA methylation refers to the addition of a methyl group to a cytosine nucleotide in a DNA molecule, but also can refer to a loss of a methyl group in other regions. Methylation affects gene expression by altering the accessibility of DNA to transcription factors and other regulatory proteins. In cancer cells, the addition of a methyl group in one location, and loss in another, can result in the silencing of tumor suppressor genes and the activation of oncogenes, promoting tumor growth and progression. As a side note, methylation is also associated with aging and a lot of research is looking at DNA methylation as a marker of unhealthy aging and disease risk. Histone modifications are another important epigenetic change in cancer. Histones are proteins that help package DNA into chromatin. Modifications to histones, including acetylation and methylation, can once again affect the accessibility of DNA to transcription factors and other regulatory proteins, with the same outcomes noted previously. Earlier, we talked about the central dogma of DNA to RNA to proteins. However, not all RNA ends up translated into protein; this type of RNA is called non-coding RNA. The term “noncoding” is a bit of a misnomer, since non-coding RNAs, such
as microRNAs and long non-coding RNAs, are also important regulators of gene expression. These RNAs can interact with messenger RNAs (mRNAs) to inhibit their translation into proteins or target them for degradation. In cancer cells, noncoding RNAs can be dysregulated, leading to the altered expression of genes that regulate cell growth and division.
WHAT TYPES OF ENVIRONMENTAL FACTORS CAUSE EPIGENETIC CHANGES? A growing body of research in human medicine looks at how the environment influences epigenetic changes. The most obvious factor is simply aging. During fetal development, epigenetic changes dictate which cells become nerve cells, muscle cells or heart cells. As we (and our dogs) age, we’re exposed to lots of substances that have the potential to cause changes. In addition, certain epigenetic changes seem to be a part of normal aging. Several lifestyle factors have been implicated in epigenetic changes and health outcomes (positive and negative), although we need to remember that some are just associated with disease and others have only been demonstrated in vitro. These factors include obesity (negative), exercise (positive), air pollution (negative), smoking (negative), polyphenols in foods (positive), alcohol consumption (negative) and emotional stress (negative).1 An intriguing — and important — fact about epigenetic changes is that they can influence the health of future generations. An often-cited example from human medicine comes from studies of Dutch women who were pregnant during the winter famine of 1944-1945. Over 60 years later, researchers found that these children, now adults, had a higher incidence of certain diseases. Further examination revealed these individuals had higher levels of methylation at some gene loci when compared to siblings not affected by the famine.2-5 There is also evidence that epigenetic changes are reversible. Another example from human medicine comes from studies of smokers. There is plenty of evidence that smoking triggers a variety of epigenetic changes, but when people stop smoking, many of these epigenetic changes reverse themselves.6 Unfortunately, things are a bit murkier when it comes to environmental factors, epigenetic changes, and canine cancer. Exposure to secondhand smoke, air pollution and smog, IVC Summer 2023
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LIFESTYLE FACTORS ASSOCIATED WITH EPIGENETIC CHANGES IN HUMANS • Diet/nutrition • E xercise • Obesity
• Smoking
• P ollutants • A lcohol
consumption
• S tress
PRIMARY MECHANISMS OF EPIGENETIC CHANGES • Altering • Histone DNA alterations through methylation
• Non-coding RNA
CANCERS ASSOCIATED WITH EPIGENETIC CHANGES • Mammary cancer • Melanoma
• Osteosarcoma
• H emangiosarcoma • H igh grade mast cell tumors
ADDITIONAL RESOURCES Horvath S, Lu AT, Haghani A, et al. DNA methylation clocks for dogs and humans. Proc Natl Acad Sci USA(2022) 119(21) doi:10.1073/pnas.2120887119:An excellent review of DNA methylation and aging. Mantaner-Angoiti E, Marin-Garcia PJ, Llobat L. Epigenetic alterations in canine malignant lymphoma: future and clinical outcomes. Animals(2023) 13:468488. doi:10.3390/ani13030468: A great review of epigenetics and canine lymphoma. Xavier PLP, Muller S, Fukumasu H. Epigenetic mechanisms in canine cancer. Front Oncol (2020) 10:591843 doi: 10.3389/onc.2020.591843 — Another excellent, in-depth discussion of canine cancer and epigenetics. The Centers for Disease Control and Prevention website (cdc.gov) has a nice section on epigenetics and human health. Some of their examples are cited in this article.
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insecticides, pesticides and herbicides have all been linked to cancer development in dogs, but the exact mechanisms remain unknown.
EPIGENETICS AND CANINE CANCER Researchers have a growing interest in studying epigenetic changes and their influence on the development of cancer in dogs. Understanding these changes could point to new treatments and possibly even preventive measures for many different types of canine cancer. DNA methylation patterns are an active area of research. Although a definitive link between methylation patterns and alterations, and cancer development, hasn’t been established, an accumulating body of evidence shows that this process is important. Several published studies have linked certain hypomethylation patterns to the development of lymphoma, leukemia, high-grade mast cell tumors, and lung cancer. Conversely, hypermethylation of other regions also have been associated with lymphoma, leukemia, and melanoma in dogs.7-17 Histone modifications also have been linked to canine cancer, specifically bladder cancer and osteosarcoma.18-22 Currently, Morris Animal Foundation has one active grant studying a mutation in the SETD2 gene, which encodes a histone methyltransferase. In this instance, methylation is important for normal function, and if mutated, the dysregulation is associated with aggressive osteosarcoma in people. This Foundation-funded study is looking at the same mutation in dogs, and determining if it could ultimately be leveraged as a therapeutic target. Non-coding RNAs also are implicated in cancer development. Most veterinarians are probably familiar with microRNAs and their association with cancer. Evidence exists for microRNA dysregulation in osteosarcoma, mast cell tumors, lymphoma, mammary cancer, melanoma, and hemangiosarcoma. MicroRNAs in the blood and urine have generated a lot of interest as cancer biomarkers that could be used as screening tools.23-30
NEW EPIGENETIC RESEARCH FUNDED BY MORRIS ANIMAL FOUNDATION In the last five years, the Foundation has seen a big uptick in the number of proposal submissions focused on epigenetics. Current projects in progress or under consideration include:
9 Epiphanio TMF, de Azevedo Fernandes NCC, de Oliveira TF, Lopes PA, Réssio RA, Gonçalves S, et al.
Global DNA methylation of peripheral blood leukocytes from dogs bearing multicentric non-Hodgkin lymphomas and healthy dogs: A comparative study. PloS One (2019) 14:1–22. doi: 10.1371/journal. pone.0211898. 10 Herrera CL, Kim DY, Kumar SR, Bryan JN. Peroxisome proliferator activated receptor γ protein
expression is asymmetrically distributed in primary lung tumor and metastatic to lung osteosarcoma samples and does not correlate with gene methylation. BMC Vet Res (2015) 11:1–11. doi: 10.1186/ s12917-015-0547-x. 11Shi H, Guo J, Duff DJ, Rahmatpanah F, Chitima-Matsiga R, Al-Kuhlani M, et al. Discovery of novel
epigenetic markers in non-Hodgkin’s lymphoma. Carcinogenesis (2007) 28:60–70. doi: 10.1093/ carcin/bgl092
12Bryan JN, Taylor KH, Henry CJ, Selting KA, Rahmatpanah F, Lewis MR, et al. DNA methylation in
• S tudying methylation for early detection and recurrence of canine hemangiosarcoma
cancer: techniques and preliminary evidence of hypermethylation in canine lymphoma. Cancer Ther (2008) 6:137–48.
• Using a DNA methylation clock to study aging in dogs
deoxycitidine in melanoma cells: Demethylation of TNF-α and activation of FOXO1. Cancer Lett (2015) 369:344–53. doi: 10.1016/j.canlet.2015.08.023.
13Noguchi S, Mori T, Igase M, Mizuno T. A novel apoptosis-inducing mechanism of 5-aza-2’-
• S tudying the therapeutic utility of SETD2 mutations in canine osteosarcoma
14Noguchi S, Mori T, Nakagawa T, Itamoto K, Haraguchi T, Mizuno T. DNA methylation contributes
• Studying changes associated with aging of the canine immune system.
15Sato M, Mochizuki H, Goto-Koshino Y, Fujiwara-Igarashi A, Takahashi M, Ohno K, et al. Prognostic
toward silencing of antioncogenic microRNA-203 in human and canine melanoma cells. Melanoma Res (2015) 25:390–8. doi: 10.1097/CMR.0000000000000183 significance of hypermethylation of death-associated protein kinase (DAPK) gene CpG island in dogs with high-grade B-cell lymphoma. Vet Comp Oncol (2018) 16:409–15. doi: 10.1111/vco.12395. 16Bronzini I, Aresu L, Paganin M, Marchioretto L, Comazzi S, Cian F, et al. DNA methylation and
We’ve even funded a few cat and wildlife epigenetic studies that could have implications for dogs as well. The Golden Retriever Lifetime Study was initiated as a cancer risk factor project. A current project involves testing urine and blood samples from dogs diagnosed with lymphoma for evidence of environmental toxin exposure. Understanding the epigenetic changes that occur in canine cancer can provide valuable insights into the underlying mechanisms of the disease, and help identify new targets for cancer treatment. Epigenetic therapies, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, have shown promise in human cancer treatment and may also be effective in the treatment of canine cancer.
targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia. Vet Comp Oncol (2017) 15:910–8. doi: 10.1111/vco.12231. 17Yamazaki J, Jelinek J, Hisamoto S, Tsukamoto A, Inaba M. Dynamic changes in DNA methylation
patterns in canine lymphoma cell lines demonstrated by genome-wide quantitative DNA methylation analysis. Vet J (2018) 231:48–54. doi: 10.1016/j.tvjl.2017.11.007. 18 Eto S, Saeki K, Yoshitake R, Yoshimoto S, Shinada M, Ikeda N, et al. Anti-tumor effects of the histone
deacetylase inhibitor vorinostat on canine urothelial carcinoma cells. PloS One (2019) 14:1–15. doi: 10.1371/journal.pone.0218382.
19Sakthikumar S, Elvers I, Kim J, Arendt ML, Thomas R, Turner-Maier J, et al. SETD2 is recurrently
mutated in whole-exome sequenced canine osteosarcoma. Cancer Res (2018) 78:3421–31. doi: 10. 1158/0008-5472.CAN-17-3558.
20 Gardner HL, Sivaprakasam K, Briones N, Zismann V, Perdigones N, Drenner K, et al. Canine
osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2. Commun Biol (2019) 2:1–13. doi: 10.1038/s42003-019-0487.
21Choi HJ, Jang S, Ryu JE, Lee HJ, Lee HB, Ahn WS, et al. Significance of EZH2 expression in canine
mammary tumors. BMC Vet Res (2016) 12:1–7. doi: 10.1186/S12917-016-0789-2.
22Choi HJ, Lee HB, Park HK, Cho SM, Han HJ, Lee SJ, et al. EZH2 expression in naturally occurring canine
tumors. Comp Med (2018) 68:148–55.
23Boggs RM, Wright ZM, Stickney MJ, Porter WW, Murphy KE. MicroRNA expression in canine
mammary cancer. Mamm Genome (2008) 19:561–9. doi: 10.1007/s00335-008-9128-7.
24Fenger JM, Bear MD, Volinia S, Lin TY, Harrington BK, London CA, et al. Overexpression of miR-9 1Alegria-Torres JA, Baccarelli A, Bollati V. Epigenetics and lifestyle. Epigenomics (2011) 3(3):267-277.
doi:10.2217/EPI.11.22.
2Roseboom T. Epidemiological evidence for the developmental origins of health and disease: effects
of prenatal undernutrition in humans. J Endocrinol (2019) 242:T135-T144.
3Heijmans B, Tobi E, Stein A, et al. Persistent epigenetic differences associated with prenatal exposure
to famine in humans. Proc Natl Acad Sci U S A (2008) 105:17046-17049
in mast cells is associated with invasive behavior and spontaneous metastasis. BMC Cancer (2014) 14:1–16. doi: 10.1186/1471-2407-14-84. 25Fenger JM, Roberts RD, Iwenofu OH, Bear MD, Zhang X, Couto JI, et al. MiR-9 is overexpressed in
spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines. BMC Cancer (2016) 16:1–19. doi: 10.1186/ s12885-016-2837-5. 26Grimes JA, Prasad N, Levy S, Cattley R, Lindley S, Boothe HW, et al. Smith BF. A comparison of
Common and Timing- And Sex- Specific. Hum Mol Genet (2009) 18:4046-53.
microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs. BMC Vet Res (2016) 12:1–12. doi: 10.1186/s12917-016-0903-5.
5Tobi E, Slieker R, Luijk R, et al., DNA methylation as a mediator of the association between prenatal
27Kobayashi M, Saito A, Tanaka Y, Michishita M, Kobayashi M, Irimajiri M, et al. Microrna expression
6McCartney D, Stevenson A, Hillary R, et al. Epigenetic signatures of starting and stopping smoking.
28 Craig KKL, Wood GA, Keller SM, Mutsaers AJ, Wood RD. MicroRNA profiling in canine multicentric
7Pelham JT, Irwin PJ, Kay PH. Genomic hypomethylation in neoplastic cells from dogs with malignant
29 Rahman MM, Lai YC, Husna AA, Chen HW, Tanaka Y, Kawaguchi H, et al. Micro RNA transcriptome
8 Morimoto CY, Tedardi MV, da Fonseca IIM, Kimura KC, Sanches DS, Epiphanio TF, et al. Evaluation
30 Ushio N, Rahman MM, Maemura T, Lai YC, Iwanaga T, Kawaguchi H, et al. Identification of
4Tobi E, Lumey L, Talens R, et al., DNA Methylation Differences After Exposure to Prenatal Famine Are
adversity and risk factors for metabolic disease in adulthood. Sci Adv (2018) 4:eaao4364. EBioMedicine (2018) 37:214-220.
lymphoproliferative disorders. Res Vet Sci (2003) 74:101–4. doi: 10.1016/S0034-5288(02)00179-0.
of the global DNA methylation in canine mast cell tumour samples by immunostaining of 5-methyl cytosine. Vet Comp Oncol (2017) 15:1014–8. doi: 10.1111/vco.12241.
profiling in canine prostate cancer. J Vet Med Sci (2017) 79:719–25. doi: 10.1292/jvms.16-0279. lymphoma. PloS One (2019) 14:1–24. doi: 10.1371/journal.pone.0226357.
profile in canine oral melanoma. Int J Mol Sci (2019) 20:1–19. doi: 10.3390/ijms20194832.
dysregulated microRNAs in canine malignant melanoma. Oncol Lett (2019) 17:1080–8. doi: 10.3892/ ol.2018.9692. IVC Summer 2023
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