Cancer In Dogs & Osteosarcoma In The Rottweiller

CANCER IN DOGS & OSTEOSARCOMA IN THE ROTTWEILER
Marlene Smith – Schalkwijk DVM
Tree of Life Veterinary Care
1777 Riverside Lane, Courtenay BC Canada
ph: 1-250-338-2316  fax: 1-250-338-8814
treeoflifevet@shaw.ca

 
Introduction.
The diagnosis of cancer is in most people’s mind a death sentence. It is one of those areas in Western Medicine where the cause of the disease is mostly speculative and poorly understood. Western medicine approach to cancer is surgery (if applicable), prednisone, chemotherapy or a combination. This can buy some time and yet rarely “cures” cancer. “Spontaneous remissions” are being reported in human as well as in veterinary medicine and as poorly understood as cancer itself. Over the last 10 years we have seen a dramatic increase in cancer in our pet population. It is now the leading cause of death in dogs over 10 years of age. The very first question we all ask is; “what is the cause of my animal’s cancer?” At this point there is no answer to this question. Genetic predisposition, environmental pollution, diet, damage to the immune system due to repeated vaccinations or excessive antibiotic use, thinning of the ozone layer, herbicide and pesticide use are all components showing up in the various research articles as possible contributors to this new epidemic.
Research shows that patients treated with immune suppressive therapy have a higher incidence of developing tumors then those not treated with immune suppressive agents. Also patients with immune mediated diseases and acquired immune deficiency syndrome (Feline leukemia, Feline Immune Deficiency syndrome, Aids) have a higher incidence of cancer. (1) And finally the use of herbicides/pesticides as T4D are quoted as increasing cancer especially lymphoma type cancers.

Summary.
This article will discuss cancer in dogs in general and more specific bone cancer in the Rottweiler.
It is the author’s belief that bone cancer so prevalent in the Rottweiler has a similar genetic background and development as histiocytosis in the Bernese Mountain Dog.

Is every tumor cancer?
There are benign and malignant tumors. Cancer normally relates to malignant tumors.
A benign tumor is characterized by a limited multiplication of cells, surrounded by a capsule. There are no rapid multiplying cells and the mitotic index (rate of cell multiplication) is zero or very low. There is an absence of malignant cells extending into the surrounding tissue. There is no chance of metastasis to surrounding tissues or elsewhere in the body.
The tumor is limited to the site and does not go anywhere. Surgical excision is curative.
Examples are lipomas, sebaceous gland cysts, warts, Histiocytoma in young dogs.
Malignant tumors/cancer.  These are characterized by rapid growth and cell division (high mitotic index), infiltration into surrounding tissue (no clear tumor margins) local or distance metastasis and reoccurrence or metastasis after surgical removal.

The immune system and cancer.
Cancer can develop in many different organs or cells and are named after the cells they develop in. Most of them have a common origin; the chronic stimulation of specific (inflammatory) immune cells.
 
Cancer specifically involving immune cells.
The following are classical immune cell type of cancers:

1. Mast cell tumors
2. Lymphoma/ Lymphosarcoma
3. Fibrosarcoma
4. Histiocytosis
5. Plasma cell tumors
6. Multiple myeloma
7. Leukemia
8. Hemangiosarcoma?
9. Small cell lung cancer?
10. Thyoma?

Other cancers are called specific organ cancers such as liver, kidney, lung, bladder cancer osteosarcoma, or glandular cancers (adeno-carcinoma’). This does not rule out however that the origin of these cancers involves specific immune cells.

The immune system.
As cancer is basically a failure of the immune system to eliminate cancer cells, it is important to look at the immune system first if we want to try and understand the cause and subsequently treatment of cancer.
The immune system evolved to protect the body from outside pathogens as well to recognize abnormal cells including cancer cells within the system.
The immune system can be divided into two parts, each of them carrying specific cells.
a) Innate cells (we are born with it) which fight bacteria and viruses. The Natural Killer cells belong to this family and destroy cancer cells. Dendritic cells and macrophages are also classified in this group. These last cells kill invaders and tumor cells through lyses (digestive granules). Macrophages come from the bone marrow/blood monocytes and are also called Kupfer’s cells or Histiocytes depending on their location.
b) Adaptive cells. These are obtained during live and acquired. Their response and development is slower. B & T lymphocytes belong to this group. These cells recognize specific antigen through their antigen receptors.

T lymphocytes are involved in cell-mediated immunity. They originate in the bone marrow and migrate to the Thymus where they mature (hence the “T” of T Lymphocytes). Beside of memory cells there are 4 other types of T cells.
B-lymphocytes are a part of the humeral immune system and come from the bone marrow. Once these cells find an antigen they absorb it via special receptors on their surface. This antigen or parts of it is displayed on the surface of the B cell, which activates the Lymphocytes to bind and secret lymphokines, which matures the Bcell. It then divides in the antigen producing plasma cells, which binds to the antigen and destroys it through lyses, using cytokines.
Cytokines are proteins secreted by immune cells to signal other cells of the immune system. Different cells secrete different cytokines as interleukine 2, 4 and 8 and interferon 8 ά and β, TN Factor (which stimulates the growth factor for the macrophages) Transforming Growth Factor, which moderates macrophages and lymphocytes proliferation (the  “turn of key”!).

Immune response to cancer
In an immune response to cancer, there is a cascade of activity involving lymphocytes, macrophages (histiocytes and osteoclasts are differentiated macrophages), interleucine, interferon, tumor necrosis factor and Natural Killer cells etc. This is a similar chain of reaction to infection! In summary it works like this: if a tumor cell presents itself as an abnormal cell, dendritic cells or other immune cells will recognize this. These cells will absorb the introdudor or abnormal cell and place a specific signal on its surface. The cell will release lymphokines & cytokines, which will attract specific lymphocytes. Binding has to take place between the dendritic cell and the Tcell, in order for the Tcell to become activated and to release cytotoxic enzymes. This activates the macrophages, which then will continue the job and destroy the abnormal cell. The release of cytokines/lymphokines or histamine creates the inflammation we can see in blood work or in the patient as fever, pain, itching, swelling etc.

How can this fail?
Tumor cells can resemble normal tissue cells and the immune system may not recognize that these cells are abnormal. Tumor cells are poorly immunogenic.
Tumors can also be immune evasive. This can happen through dysfunction of the immune system.
The earlier described binding process can be inhibited by immune suppression, tumor blocking antibodies, and some tumors producing a protein on the surface of their cells mimicking embryonic protein! (2). Some tumors (prostate is an example) will produce arginase, an enzyme which de-activates arginine, necessary for the immune system to function properly. Interestingly enough the bacteria Helicobacter, involved in chronic gastritis and gastric ulcers and IBD also produces arginase; so does Mycobacteria! It is amazing how sophisticated some of these tumors are in avoiding recognition and destruction by the immune system!

There can be a defect in the Antigen Presenting Cells as the Dendritic cells, Macrophages or Histiocytes, which is the case in histiocytosis. Tumors can also produce hydrogen peroxide or nitric oxide, which kills the dendritic cells.

Causes of cancer

From the above it is clear that from a Western (medicine) scientific perspective the causes of cancer are complex and are mutifactoral. It is not a process that happens overnight; it is a slowly developing time bomb waiting to go off at an opportune moment.
Three main factors are being pinpointed as possibly contributing to cancer.

1. Genetic predisposition

Specific forms of cancer have a high incidence in specific breeds or family lines, which points towards a genetic predisposition.
 Some examples of genetic predisposition of cancer:
A specific line of English Cocker Spaniels developed immune mediated glomerulo nephritis. They all developed anal gland adeno-carcinoma with metastasis to the regional lymph nodes. Over 80% of this family was affected. Western oncologists have no explanation for this phenomena.

Genetic (?) anal gland adenocarcinoma in a litter of English Cockers, all three dogs are affected

Some lines of Golden Retrievers show a very high incident of Lymphosarcoma or hemangiosarcoma, with the majority of the members of these lines dying of this specific type of cancer. The interesting part of this is that almost all animals would show cancer at a specific age!
The Rottweiler has a very high incidence of Osteo-sarcoma.
The Bernese Mountain Dog, Flat Coat and Golden Retriever have an above average of Histiocytosis (Malignant Histio/ Disseminated) in their breed, with the Berner topping it with 80% of all cases of Histiocytosis
The question is here, if the cancer is encoded on the gene’s, why does it not express itself in the first stages of development or during the rapid growth spurt, when the DNA is duplicated many times?
Most researchers agree that a trigger seems to be needed to set of a cascade of immune failure resulting into cancer.
DNA data base of all breeding stock and tagging incidence of osteosarcoma will help us understand the genetic link to osteosarcoma in the Rottweiler. A project worth while!

1. Immune system damage by herbicides and pesticides. Studies have shown an increase in cancer (specifically lymphosarcoma) in area’s where there is a higher exposure to pesticide such as T4D (7). We may have to take a careful look at the food we feed our dogs especially its preservatives for long term shelf use. A comprehensive study in populations or raw fed dogs (especially 3-5 generations) and their incidence of cancer would be most worthwhile in this perspective.

Vaccination protocols also may need a very careful examination as research has shown that repeated vaccinations can contribute to immune mediated thyroiditis (13).

1. Idiopathic causes.

This simply means we don’t know the cause. Heavy breeds as Rottweiler and the Mastiff (and of course there is a relationship between the Mastiff and the Rottie) seem to be more predisposed to osteosarcoma then small and light weight dogs. Extra (excessive) weight bearing as in dogs with previously amputated limbs or previous surgery with “hard ware” in their legs (for fracture repair) also seem to be more predisposed.

Osteosarcoma

.
Histiocytosis is an interesting form of cancer as it is clearly an immune induced disease.
Understanding what sets of the cascade of events in Histiocytosis may help us to understand better how cancer starts and how we can treat it in a more specific and directed way then the current chemotherapy approach. The author also believes that osteosarcoma in the Rottweiler follows a similar genetic trait and cancer development as Histiocytosis in the Bernese.

Histiocytosis in Bernese Mountain Dogs

Histiocytosis is characterized by an abnormal multiplication of histiocytes.
What are Histiocytes?
Histiocytes have different names depending on their location.
Macrophages (in blood and bone marrow)
Dendritic cells (skin, mucosa, connective tissue)
Kupfer cells in liver
Microglia in the brain
Osteoclasts in the bone (marrow)
Langerhan’s cells in the skin (dermis)
Type A synovial cells in the joints

They all come from the monocytes (watch the monocytes count in the CBC) and differentiate in the phagocytotic cells.

Histiocytes, dendritic cells or osteoclasts and Osteosarcoma in the Rottweiler
The macrophages/histiocytes/dendritic cells/osteoclasts have as main purpose in life to ingest, breakdown and digest (phagocytosis) of microorganism, cell debris, damaged cells and abnormal (cancer) cells. Osteoclasts and dendritic cells are also antigen-presenting cells (APC). They present the surface of the ingested “culprit” to the immune cells (lymphocytes and macrophages) in the blood. This process releases cytokines (inflammation = fever), which attracts T lymphocytes. This will activate the T cell and macrophages are attracted and activated, which then destroy the cancer cell.
Resent research at UC Davis by Peter Moore & all seems to indicate that in Malignant Histiocytosis (Bernese Mountain Dog) there is a problem with the binding mechanism between the APC and the T cell.

The continuous release of cytokines creates the inflammation and fever we see in dogs with Malignant Histiocytosis. Multiplication of the histiocytes or osteoclasts likely occurs via the stimulation of cell surface growth hormone. We now can see bone tissue being replaced by osteoclast which shows up on radiographs as “black holes” or lyses. The patient may limp on and of due to the inflammation and pain caused by the cytokine release. We may not see the cauliflower appearance on radiographs at this time.
Most chemotherapies Cyclophosphamide (Cytoxin) or Cyclosporin, Doxyrubricine etc will inhibit cell reproduction as well inhibit T cell production. This will reduce the inflammation and tumors may actually shrink. However the absence of T cells could stimulate the APC to produce more cytoxin and stimulate their own growth hormone leading to more APC cells as osteoclasts. When we stop the chemotherapy the same process may start all over again.
As discussed above the latest research in Histiocytosis in the Bernese shows likely a genetic defect in the ability to form proper binding between the APC and the lymphocytes. The continued release of cytokines creates continued inflammation and stimulation of the immune system, which eventually results in the immune system attacking its own tissue. In Histiocytosis this is often the platelets (which lead to fatal bleeding) and/or the red blood cells leading to progressive immune mediated anemia.
In a similar scenario in osteosarcoma normal bone tissue is replaces with osteoclasts tumors and abnormal bone tissue. This weakens the bones and leads to fractures.
If the above hypothesis is true, it explains why chemotherapy and amputation rarely “cures” osteosarcoma.

Treatment and prevention

Prevention is the best form of treatment.
Genetic predisposition tells us to carefully scrutinize breeding stock, have a DNA bank with a database linked to osteosarcoma. Yet another thing to think about when you look for a suitable partner to your breeding bitch or stud dog!
Avoiding the use of pesticides especially T4D on lawn, household and environment.
Support studies in vaccination protocols that protect the animals and not tax their immune systems. Studies performed by Dr. Jean Dodds (Rabies Challenge study) and Ron Schultz are worthwhile project to support and sponsor (13)!
Be vigilant and recognize possible early osteosarcoma at a very early stage.
As far as treatment is concerned, it is the author’s belief that there is a big future in the integration of western, oriental, botanical medicine and homeopathy!
There are several reports of the successful treatment of early osteosarcoma using vitamin A/D in high dosage, Hoxey Formula, Medicinal Mushrooms restricted exercise and specific Chinese herbal formula’s formulated for the individual patient and presentation (15).

References:

1. Cancer and the Immune System, Marlene Smith-Schalkwijk DVM AVAC Calgary July 28 1999
2. Veterinary Immunology, Ian R Tizard.
3. A Holistic Approach to Cancer with Traditional Chinese Medicine, Cheryl Schwartz DVM Galgary AVAC July 28 1999
4. Biology of Belief, Bruce Lipton www.brucelipton.com
5. Treating cancer with Chinese Herbs, Hong-Yen Hsu, PH, D, Oriental healing Art Institute. (Translation of Chronic and Recalcitrant diseases by Dr. Hong-Yen Hsu. Printed in Taiwan)
6. Nutrition and Cancer: Frontiers for Cure! Gregory K Ogilvie, DVM, Dipl. ACVIM American Holistic Veterinary Medical Association 1998 New Orleans
7. Controversies in Veterinary Oncology: Complementary/ holistic Cancer Therapy- Fact or Fiction? Gregory K Ogilvie D.V.M, Dipl. ACVIM ; American Holistic Veterinary Medical Association New Orleans 1998
8. Managing the Veterinary Cancer Patient. Gregory K Ogilvie, Antony S Moore. Veterinary learning Systems 1995.
9. Cancer vaccines Preeti, Gokal & Kochar www.csa.com/discoveryguides/cancer/abstract/
10. www.histiocytosis.ucdavis.edu/sarcoma.html
11. Canine Hemophagocytic Histiocytic Sarcoma. P.F. Moor, V.K Affoter & W. Vernon U.C. Davis Vet. Pathology 43:632-645 (2006)
12. Dr Candace Pert, Molecules of Emotions www.candacepert.com
13. Jean Dodds DVM Hemopet (rabies challenge fund)
14. Vet. Therapeutics vol 5 no 3 Fall 2004
15. Longer then expected survival using a novel integrative approach to hospice in a case of canine osteosarcoma. R Palmquist DVM and R Goldstein VMD JAHVM vol 28 number 1 page 16 2009
16. “A Holistic Approach for the Treatment of Cancer “ Joe Demers DVM, CVA, CVH  Journal of the American Holistic veterinary Medical Association January 2005 Vol. 23 number 4 page 31
17. Naturopathic treatment of osteosarcoma. Steve Marsden DVM, AHVMA conference 2000.
18. A Holistic Approach for the Treatment of Cancer “ Joe Demers DVM, CVA, CVH  Journal of the American Holistic veterinary Medical Association January 2005 Vol. 23 number 4 page 31

Back to articles