Man’s Best Friend, The Dog: A Model for Cancer

The Dog: A Model for Cancer

With cancer being the number one cause of death for our dogs and cats here in America, as well as it being the second highest cause of death in humans, the prospect of encompassing the ideology of One Health, which is the integrative effort of multiple disciplines working locally, nationally, and globally to attain optimal health for people, animals, and the environment, can be incredibly helpful in fighting such a deadly disease.

Another topic that will be addressed is using holistic treatments for cancer. This is also, in a way, how the environment can play a part in the treatment of cancer using plants and nutrients to help battle this disease.

Dogs have been known as mankind’s best friend, and for good reason. Because dogs experience and share many of the same things we do, such as eating the occasional table scrap, exposed to similar carcinogens, and even sleeping in the same bed, dogs develop many of the same diseases we do. When comparing DNA and protein sequences to humans, canines are actually more similar than mice are. This makes the dog an excellent candidate to become a model for cancer.

dog humans cancer
Are humans and dogs fighting the same battle against cancer?

The Importance of Canine Genome Mapping

Currently, there are around 400 different breeds of dogs. Through selective breeding, this has inadvertently created many “founder” mutations that have been associated with particular traits and diseases. By doing this and reducing genetic heterogeneity, this has created both a problem and a research opportunity in that most popular breeds are predisposed to develop a specific set of diseases or cancers.

Since linkage disequilibrium, or a nonrandom association of alleles at two or more loci, can be up to 100-fold greater in dogs than humans, single breeds can be used successfully in broad genetic mapping and disease research. Breeds with similar lineage who share an important trait are useful for fine mapping.

A study was conducted which included 57 quantitative morphological traits in 915 dogs, which included samples from 80 breeds. Traits that were included were body size, external dimensions, as well as the size and shape of the cranial, dental, and long bones. When compared to humans, it was found that one to three quantitative trait loci were responsible for almost all of the phenotypic variation in most dog traits examined in the study.

With this thinking, it may be possible that canine complex diseases will be similar in that they will also be confined to a small segment of genome.

what is the dog genome
The canine genome defines the breed, the look, and several other parameters, including genetic predispositions to specific diseases and cancers.

Cancer in Canines

Soft tissue sarcomas

Soft tissue sarcomas afflict about 1% of human cancer patients and represent a heterogeneous group of mesenchymal neoplasms. This type of cancer usually shows a wide range of clinical presentations and cellular morphology, making it that more difficult to treat efficiently.

Two fibrosarcomas were taken from Labrador Retrievers and had shown large chromosomal rearrangements, amplifications, and deletions, something human fibrosarcomas show as well . Deletions of CDKN2A and CDKN2B, like in the Labrador fibrosarcomas, have also been observed in other types of human cancers. This is an important discovery and could be used to further show how and why particular common pathways and genes are responsible for the development of certain types of cancers in dogs and humans.

Osteosarcomas

Osteosarcomas are the most commonly diagnosed primary malignant tumor of the bone. Over 56% of all bone tumors are osteosarcomas in humans and are the third most frequently diagnosed cancer in children. 10,000 dogs are diagnosed annually with this same cancer in the United States alone and occurs 20 times more frequently in dogs.

Nothing less than 85% of bone related malignancies in large and giant dog breeds are osteosarcomas, these dogs having a 61 times higher risk compared to other breeds. Survival rate is exceptionally low for this type of cancer, with many patients being unresponsive to chemotherapy, the same treatments being used in both humans and dogs.

Osteosarcomas in dogs are similar to the human form in that both have similar histology and response to treatment. Dog models for this cancer showed its first success in clinical trials focusing on limb salvage techniques, these techniques are now used in human medicine. Since human and canine osteosarcomas have a 75% aneuploid DNA index and share similar genetic alterations, the canine model can be used to encompass this human cancer very effectively.

Lymphomas

In the United States, lymphomas represent about 5% of afflicted human and dog cancer patients. The incidence of new hodgkin’s lymphoma has been increasing in past years with no known reason, which is why new models for lymphoma could be useful in determining the cause as well as furthering insight into the cancer’s biology.

canine lymph nodes
CANINE LYMPHOMA: these are the lymph nodes to monitor

It is believed that this type of cancer is very similar in its flawed genetic state in both dogs and humans. The same type of chemotherapy is even used to treat diffuse large B-cell lymphomas, the most common type of NHL, for dogs and humans. Lymphoma is the most common life-threatening cancer in all dogs (24% of canine cancers) as well as it having high prevalence in certain breeds, such as 1 in 4 Boxers and 1 in 8 Golden Retrievers affected.

Recently, a study was conducted to treat lymphoma in dogs using anti-human leukocyte antigen (HLA)-DR monoclonal antibody (mAb). Results using humanized IgG4 anti-HLA-DR were successful in binding to malignant canine lymphocytes, with human clinical trials underway. This only provides an increasingly solid foundation in why using dogs with lymphoma is so promising in ensuring the safety and effectiveness for cancer therapy in our pets, as well as ourselves.

The Dog Is a Relevant Model For Cancer Genetics

Although this particular review focused on the relevance of the dog as a model for research in cancer genetics, research in the field of biomedics has used the canine model for many diseases and treatments that are compatible with people.

Dogs have also been used more in areas like behavioral research, such as the capacity for learning and social cognition. Other research has covered how diet plays a role in behavior enrichment on executive functioning, which is the cognitive process that includes working memory, reasoning, task flexibility, and problem solving.

Using the dog as a model for many of our own ailments has proved to be unparalleled in understanding certain diseases and how to better treat them. In turn, this will ultimately lead to better health care management in humans as well as dogs, a win win situation.

Alternative Approaches to Cancer Treatment

list foods vitamin c dogs
A list of foods providing a great amount of Vitamin C. This is for humans, but most are good in moderation for dogs, too.

Vitamin C: The Unsung Hero

Humans lack the ability to synthesize our own vitamin C from glucose due to L-gulonolactone oxidase deficiency. Because of this, vitamin C must be obtained from our foods and from supplements. This nutrient is also important in that is is needed for the synthesis of L-carnitine from lysine, neurotransmitters synthesis, cytochrome p-450 activity, cholesterol metabolism, detoxification of exogenous compounds and is also an antioxidant.

It has been shown that the levels of vitamin C in the blood of cancer patients is much less compared to a healthy individual, meaning that cancer patients require an increased amount of vitamin C.

Contradictory Studies

Over 60 years ago marked the first time vitamin C was recommended for use in cancer treatment by Dr. Klenner. Since then, there have been hundreds of studies covering in vitro, in vivo, cell culture, animal, and human studies exploring the potential of vitamin C’s cancer fighting potential with mixed results.

A study conducted by Cameron et al. concluded that administering high doses of vitamin C improved longevity and quality of life in cancer patients. In later years, another study conducted by Creagan et al., one of several studies funded by the Mayo Clinic, stated that vitamin C had no apparent effect on cancer patients, and having such a foothold in the scientific community, their word was taken as true.

The major difference between these two studies, being of great importance, was that the study conducted by Cameron gave patients vitamin C intravenously while the Mayo Clinic study were giving patients vitamin C orally. The absorption rate of vitamin C given orally, even with very large doses, can raise plasma vitamin C concentrations to a maximum of about 220 micromol/L. Intravenous administration on the other hand can result in plasma concentrations as high as 26,000 micromol/L, a very significant difference.

Improve The Quality Of Life Of Terminal Cancer Patients

Improving the quality of life in patients afflicted with terminal cancer is of great importance as well. This study examined how quality of life was affected in terminally ill cancer patients after treatment with high-doses of vitamin C. In those who have been given less than six months to live, quality of life is as important as a cure.

The treatment method in this study for cancer patients was focused on well-being as well as minimizing unpleasant symptoms, making the ultimate goal of this study focusing on a treatment that could be used in conjunction with other cancer fighting remedies.

The research pool consisted of all 39 patients having stage IV cancer, with 12 patients having a recurrence of their cancers. None of the patients were excluded because of side effects to the vitamin C. All patients were given 10 g of vitamin C intravenously twice every three days and a daily 4 g oral supplement for a week. The quality of life before and after administration of high dose vitamin C was calculated using a global health/quality of life scale, with the mean health score improving from 36±18 to 55±16 after administration.

In functional scales, patients claimed that their scores in areas such as physical, emotional, cognitive, and social function had all increased significantly. Also, patients reported significantly lower scores for fatigue, nausea/vomiting, pain, sleep disturbance, and appetite loss post vitamin C. Other considerations in the article included financial impact and resulting symptoms such as dyspnea, constipation, diarrhea, etc. These other considerations did not experience much change, if any, after administration of vitamin C.

Vitamin C, A Pain Reliever?

Besides its ability as a possible anticarcinogenic nutrient, vitamin C has also been shown as having pain relieving qualities and can be explained by various mechanisms.

First, vitamin C has shown anti-inflammatory effects through production of c-AMP, resulting in elevated production of steroids due to adrenocorticotropic hormone stimulation. Also, vitamin C has the ability to decrease blood calcium levels and direct calcium uptake in the bone. This constitutes as pain relief in the bones themselves. Studies have also shown that vitamin C increases the body’s ability to produce energy. This ability is most likely due to the vitamin’s oxidation reduction potential, which is capable of providing necessary electrons to the electron transport system in the mitochondria, meaning an increase in energy production.

With the multitudes of conflicting data over the ability of vitamin C’s use in treating cancer, the results of the study were that this nutrient was safe and showed large improvements in the quality of life in those afflicted with terminal stages of cancer. If anything, the worst IV vitamin C therapy could do for a cancer patient are minute compared to the ravaging treatments of chemo or radiation on the body. Future studies need to be conducted comparing the effectiveness of IV versus oral therapy and their results.

vitamin c cancer treatment
Vitamin C causes degeneration and the death of cells by oxidation. (credits: jaconello.com)

Vitamin C For Animal Cancers

Studies in animals have shown mixed results, though many who have experienced vitamin C administration for their pets claim great results.

Smith Ridge veterinary center is one of many veterinary practices around the country who perform IV nutrient therapy, which is a mixture of vitamins that also contains vitamin C. This treatment has been used on pets suffering from severe inflammation, such as allergies and most importantly cancer.

After three days of IV therapy, most animals, even the ones who are extremely ill, will exhibit renewed vigor, increased appetite, and symptom relief. This clinic claims to have helped thousands of pets with this type of treatment over the last 25 years with great success.

Cures for Cancer Found in Nature

Recent advances in the field of herbal medicine and cancer treatment by use of nanotechnology and how it can enhance the bioavailability as well as reducing side effects of these treatments is a rather new topic in research. Many herbal medicines have shown to be safer and less toxic than some of their synthetic drug counterparts.

This has caused herbal remedies to gain popularity and has led to substantial growth in the field of phytopharmaceuticals. Only recently has data on therapeutic and toxic activity of herbal medicinal products become available. With advances in analytical technology, this has led to the discovery of many new active compounds in medicinal plants and is still a growing field of interest.

Proper dosage for herbal treatments is another area that has had little research and will have many benefits once this type of information has been gathered. The ability to nanoformulate herbal drugs will ultimately improve component solubility, increase the absorbency by the patient, reduce medicinal herb dose waste, and possibly achieve steady therapeutic levels over an extended time frame.

Research Is Just Getting Started

Seeing that around 80% of immunosuppressive and anticancer drugs have origins from plants, “Nanotechnological Approaches to Herbal Drugs Used in Cancer Therapy” lists almost 30 different plants that are known to have anticarcinogenic potential, some of which are currently undergoing clinical trials. This article also explains how herbal remedy research has expanded with the use of several different approaches in nanotechnology and an increase in effectiveness of drug delivery methods.

Solid lipid nanoparticles offer an alternative drug delivering ability, are easy to produce, and allows better molecular stability and decreases degradation. Since liposomes are made out of the same material as cell membranes, they can be used as vesicles in the delivery of drugs for cancer and other diseases. Also, the use of nanoemulsions in the preparation of nanoparticles has also been used for controlled drug delivery and targeting. Drug discovery using herbs and plants is still very useful and a popular field of study, showing much promise with new discoveries happening frequently.

This study shows that medicinal plants are crucial in combating many diseases through drug discovery. Previous animal models have demonstrated the anticarcinogenic properties of various herbal plants and plant extracts. It also included how nanoformulation systems are important in its ability to increase the effectiveness of herbal remedies that may be poorly soluble, poorly absorbed, or easily broken down.

Advancements in the field of herbal remedy research using the nano formulations of various chemopreventive agents such as curcumin, resveratrol, genistein, vincristine, and others, is still a new and expanding area. Future studies may bring excellent alternatives to chemotherapy and radiation, though the use of several anticarcinogenic herbs has an increasing following of believers due to obvious results in both pets and people, regardless of scientific literature.

Essential Oils: A Treatment for Cancer

Another approach in the treatment of disease, including cancer, has been the use of essential oils. Essential oils, or EOs, are obtained by steam distillation or expression from herbs or medicinal plants and are a complex mixtures of molecules belonging almost exclusively to terpenoids and phenylpropanoids. The familiar antitumoral Taxol, which is extracted from the Pacific yew, Taxus brevifolia, is a type of diterpenoid derivative.

Terpenoids have been the focus of several studies in how they impact important diseases in humans. One such study was the positive effects of terpenoids in cardiac ischemia/reperfusion associated with oxidative stress inhibition. When patients were given an oral preparation of Ginkgo biloba extract, a species of tree, it resulted in controlling the side effects of myocardial ischemia and improved myocardial functional recovery as little as fifteen days after the start of the study. Free radical formation was inhibited by the extract, rather than destroying free radicals that were already present in the body. Though some studies vary, G. biloba has also shown some success in treating memory disorders such as Alzheimer’s.

essential oils for dogs
Beneficial effects of common essential oils. (credits: naturalhealthyconcepts.com)

Clinical Studies Still to Confirm EOs' Effect on Cancer

The effect of terpenoid use as a treatment for cardiovascular and neuronal diseases has had success in clinical studies and positive results in patient settings. That being said, the effects of terpenoids and EOs in general on cancer is still relatively untouched in clinical studies, though 35 years worth of documentation states its effectiveness.

The antitumor abilities of many chemotherapies is partly due to the ability of these drugs to induce an overproduction of reactive oxygen species (ROS) in tumor cells, causing cellular damage and apoptosis in these cells. Since chemotherapy is designed to prevent tumor cells from rapidly reproducing, other rapidly dividing cells, like blood cells and lymphocytes, as well as cells responsible for hair growth and maintaining the intestinal epithelial walls, are inadvertently affected. This type of bodily cellular destruction, both of the tumor cells and good cells, results in common side effects such as hair loss, infections, anemia, and thrombocytopenia. With such severe consequences to treat cancer, alternative and complementary treatments are becoming increasingly popular.

Through the discovery of anticancer natures of some EOs, this makeups a particularly interesting section of natural cancer remedies. Using highly resolutive gas chromatographic techniques, the chemical compositions of EOs can be analyzed on an extremely detailed level.

Overall, the structures that make up EOs tend to be rather simple, but through the combination of small molecular weight with a globally apolar character results in a high rate of absorption in the body. Because EOs are used as natural food ingredients and as fragrance for perfumes and soaps, their toxicological profile has been researched extensively, with most lacking any type of acute toxicity.

Many studies focusing on several terpenoids and aromatics found in EOs have shown various effects on cancer cells, including reactivating the signal for apoptosis and reducing tumor vasculature. Abilities such as these could be used in conjunction with current therapies. Research based on discovering the antitumoral abilities of EOs is still a rather new area of study.

Luckily, the hunt for cancer treatments better than chemotherapy has spurred an increased interest in the medical field to pursue concepts like herbal remedies and use of essential oils.

Holistic Alternatives

Holistic medicine is a very underrated form of cancer treatment. For many Americans, because alternative methods are not practiced by many doctors due to a lack of knowledge or training in the use of these methods, they believe it to be a sham.

An increasing amount of people have started giving these “quack” doctors another look, both for themselves as well as for their pets. Veterinarians with extensive education and experience using non-traditional medicine can be an invaluable resource when treating a pet who has cancer. Because diseases like cancer can vary between patients and treatment options may not work for every patient, encompassing several options to beat the disease is beneficial.

The use of supplements has been used to preserve, protect and support the health of pets regardless if they are ill, but pets who are sick reap the benefits of additional supplements since they often have reduced essential nutrient absorption. Another step that holistic veterinarians recommend is a change in diet to one that is rich in antioxidants, fatty acids, and amino acids. This is unfortunately not something many cancer patients are told to do, in human or animal medicine.

Use of Poly-MVA

Another alternative treatment option used in animal medicine is using Poly-MVA. The Wartburg theory states that cancer cells have an irregular electron transfer system, which can be potentially corrected using Poly-MVA. Poly-MVA combines vitamin lipoic acid palladium, and is also known as DNA reductase.

Merrill Garnett developed this “electro-active” drug and has studied and improved the compound through research spanning over 35 years. He claims it can destroy malignant tumors while ignoring healthy cells. His research has focused on finding pathways that alter electron flow in tumor cells. In laboratory experiments, they were able to prove that introducing synthetic mimics of electric pathways was successful in destroying cancer cells. Ozone therapy has also been used in cancer treatment for dogs.

This concept works on the idea that anaerobic microbes responsible for cancer will undergo total immersion of ozone, since oxygen is lethal to anaerobic organisms. Intravenous fluid solution of ozone is the most common way of administration, though it has been used topically as well. There are many alternative treatments options available for our pets that is also routinely performed in human medicine by doctors with holistic and alternative medicine training.

In Conclusion

One Health has become increasingly vital in furthering research to cure cancer, in both dogs and humans. Since cancer is so deadly and affects so many species, it was only a matter of time before the link, or better yet the bond, between humans and canines was fully comprehended.

Future research and use of alternative and holistic remedies to treat and possibly defeat cancer may be hidden in our very own furry best friends.

References

  1. Rowell, Jennie L., Donna O. McCarthy, and Carlos E. Alvarez. 2011. “Dog Models of Naturally Occurring Cancer.” Trends in Molecular Medicine.
  2. Creagan ET, Moertel CG, O’Fallon JR, Schutt AJ, O’Connell MJ, Rubin J, Frytak S.
  3. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.New England Journal of Medicine.
  4. Yeom, Chang Hwan, Gyou Chul Jung, and Keun Jeong Song. 2007. “Changes of Terminal Cancer Patients Health-related Quality of Life after High Dose Vitamin C Administration.Journal of Korean Medical Science. The Korean Academy of Medical Sciences.
  5. 2012. “Intravenous (IV) Nutrient Therapy.” Smith Ridge Veterinary Center.
  6. Qadir, Abdul, Nida Khan, Satya P. Singh, Juber Akhtar, and Muhummad Arif. 2015. “Nanotechnological Approaches to Herbal Drugs Used in Cancer Therapy.Intl. J of Pharmaceutical Sciences & Research. <10.13040/IJPSR.0975-8232.6(10).4137-44>.
  7. Lesgards, Jean-François, Nicolas Baldovini, Nicolas Vidal, and Sylvia Pietri. 2014. “Anticancer Activities of Essential Oils Constituents and Synergy with Conventional Therapies: A Review.” Wiley Online Library. Phytotherapy Research.
  8. 2015. “Ginkgo: MedlinePlus Supplements.U.S National Library of Medicine.
  9. 2010. “Using Alternative Therapies to Fight Pet Cancer.” Mercola.
  10. Additional information on multiple studies conducted by the Mayo Clinic concerning Vitamin C.

— Josette Wilsey (July, 2016)

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