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Preface   This book covers most of the topics with latest information on canine cancer in general and canine mammary cancer in particular. The book is divided into 21 chapters covering almost all aspects of canine cancer including its overview, occurrence, etiology, classifications, polymorphism, radiological-immuno-hormonal-sex hormone profiles, enzymatic-genetic-tissue prognostic markers and different modern diagnostic and therapeutic approaches. This book also includes different research findings on canine mammary cancer. The main objective of this book is to provide the latest information to meet the requirements of not only undergraduate and post-graduate students but also to the teachers and clinicians involved in canine practice. The book contains more than 150 good quality colour photographs of canine cancer, cancer diagnosis and cancer treatments. This book would be of immense use to the students, teachers and practitioners engaged in the field of cancer research and treatment.

A tumour/neoplasm is caused by a purposeless multiplication of living cells. The word neoplasm means new growth. Tumours are common in carnivore as compared to other animals. Horse and cattle are mostly affected than sheep, pig and goats. Old animals are affected more commonly than young ones. Cancer, according to current opinion, is a multitude of different diseases and is no more a “one diseases’. Myriads of tumour types and plethora of their patho-physiology in different species necessitates species wise study of tumours in detail.  Of all species, dog develops cancer twice as frequently as humans. Mammary tumours rank second (behind skin tumours) as the most common neoplasm in dogs and constituting more than 50% tumours in bitches.

Canine mammary gland tumours are the most common type of tumour in the intact female dog. Of all species, dog develops neoplasm twice as frequently as humans, with incidence of skin and mammary tumours being the highest. Tumours of mammary gland are the most common tumours of female dog representing approximately 30-50% of all tumours in bitch and it is the second most common tumour in dog after skin neoplasm and most common malignant tumour in dog. Defination Mammary gland tumours arise primarily in the female animal from secretary epithelial, myoepithelial, or, less frequently, mesenchymal elements of mammary tissue.

Cancer remains a challenge because of its incurability and fatality.  Cancer is one of the leading causes of death in companion animals such as dogs and cats and is particularly common in animals that live 10 years or longer. Of all species, dogs develop neoplasm twice as frequently as humans, with incidence of skin and mammary tumours being the highest. Data on incidence rates are relatively new development in the veterinary medicine. One of the major sources of various dog neoplasm incidence rates has been a population based animal tumour registry. Though, majority of epidemiological studies have been reported from various countries, in India knowledge about epidemiology of canine neoplasm is scant.

The breeds of animals are utilized for this study includes Spitz (12), German shepherd (7), Non descript (5), Doberman (2), Rottweiler (1), Labrador (1) and Pomeranian (2) (Total 30 clinical cases of CMT). The animals are weighed between seven to thirty nine kilograms. There are twenty three cases of non spayed and seven cases of spayed dogs. Out of thirty clinical cases of mammary tumour presented, 10 cases (33.33%) have multiple growths, and 20 cases (66.67 %) have solitary growths, pedunculated growth are 12, remaining eighteen growths are sessile. Ulcerated and inflamed are 36.67 % (11/30), and non infected are 63.33% (20/30).The surface of tumour is nodular in eight cases (4.18). Recurrence are recorded in 4 (13.33%) cases whereas, first time occurrence are 26 (86.67%).

Cancer has gained considerable relevance in animals now-a-days owing to the increased awareness among people towards animal sufferings and pain. The diagnosis and management of neoplasm, therefore, represent the major challenges faced by a veterinary oncologist. Mammary gland tumours are among the most common canine neoplasm, but the vast majority of these tumours occur in intact female dogs. In canines, mammary gland tumours that occur in males ranges from 0-2.7% (average < 1%). Sex hormones plays a vital role for the occurrence of mammary gland tumours. The p53 gene over expression is an independent factor for indicator of worse prognosis in canine mammary gland tumours. The p53 may be useful prognostic markers for evaluating malignancy in canine mammary gland tumours. There is a strong positive correlation between expression of cyclooxygenase-2 (Cox-2) and grade of malignancy in the tumours. Increased Cox-2 expressions are linearly related in the canine mammary gland tumours and are also related to worse prognosis and shorter overall survival. Canine mammary gland malignant tumours have the highest values of Cox-2 expression. Matrix metalloproteinase (MMPs) are a family of zinc and calcium-dependent proteolytic enzymes that degrade macromolecules of the extracellular matrix. Members of this family such as MMP-2, -9 and -7 have been shown to be associated with tumour progression and invasion in human cancer tissues. Matrilysin (MMP-7) influence the early stage of tumourogenesis.

Cancer has gained considerable relevance in companion animals nowadays owing to the increased awareness among the people towards animal sufferings and pain. A proper diagnosis augments a better treatment regime for the suffering animal. Of all species, dog develops cancer twice as frequently as humans. Mammary tumours rank second (behind skin tumors) as the most common neoplasm in dogs but constituting more than 50% tumours in bitches. All suspected growths therefore requires careful appraisal lest it be cancerous. Diagnosis of cancer represents one of the major challenges faced by the small animal veterinarian. In majority of instances, the differentiation of a benign from the malignant tumour can be made morphologically with considerable certainty and for the same, histopathological examination remains the gold standard. A proper histopathological diagnosis however depends a lot on the collection, fixation and processing of tissues. So clinician as well as histopathologist has their own role to play in the final diagnosis of cancer in animals.

Microsatellites are highly polymorphic repetitive DNA sequences that are randomly distributed throughout eukaryotic genomes displaying high levels of variation and consequently, are ideal for deciphering genetic variability. They are having high mutation rates (1-4 per generation). Among the microsatellite, (CA) n repeats occurring about one in every 30 kb of mammalian genome constitute useful genetic markers, as their polymorphism is sufficiently stable and their mutation rate are low enough. Out of innumerable microsatellite, ZuBeCa3 microsatellite shows huge variability in the canine genome (Switonski and others 1998). This microsatellite is located in chromosome 9q21-q22 and vastly studied in different dog breeds depicting its heterogeneous distribution over the chromosome (Switonski and others 1998).

Mammary tumours arise from the ducts are called as ductal or ductular carcinoma. Some include other tissues such as the myoepithelium and connective tissue between the glands. These have a number of different names including carcinosarcoma, carcinoma or sarcoma in benign tumour, complex adenocarcinoma and malignant mixed tumour. Tumours are also classified by the type of epithelial growth because this influences the probability of recurrence. Tumours that only have myoepithelium or connective tissue are called sarcomas.

Mammary tumours are the most frequent neoplasia in female dogs; therefore, these tumours represent a serious problem in veterinary medicine. Many tumours presented activated genes which are not normally expressed in the tissue from which they originate. The proteins derived from the expression of these genes are called tumour markers. Detection and measurement of these proteins are used in medicine for diagnosis and assessing the evolution of the tumours.

MMPs are a family of zinc-containing, calcium-dependent endopeptidases secreted by various cell types and implicated in a wide range of physiological events (e.g. trophoblast invasion, development, endometrial remodeling, ovulation, angiogenesis, wound healing, bone resorption and cell migration) as well as in pathological processes. Matrix metalloproteinase (MMPs) and their tissue inhibitors (timps) have been strongly implicated in the pathogenesis of many types of human cancer. Expression levels for the most relevant MMPS are confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The activities of MMPs are significantly higher in malignant tissues than benign canine tumours.

Sex hormone plays a vital role in the occurrence of canine mammary cancer. It is well established that canine mammary cancer is sex-hormone dependent. The risk of developing canine mammary tumour is 0.05% if the dog is spayed before its first estrous and the risk of developing a mammary cancer is increased as the number of estrous cycle increases. Mammary cancer is often hormone responsive, since growth or regression of tumours can be modulated by suitable hormonal manipulations. Estrogen and Progesterone appear to be major hormones in regulation of mammary tumour development. It is also reported that about 40-50% malignant mammary tumour in the dog have either or both estrogen and progesterone receptors. Benign tumours in dogs have also female sex hormone receptors and they can be stimulated by hormonal cycling. Mammary carcinoma can be induced in male and female rodents by administration of estrogen. Transsexual males given high doses of estrogen to induce mammary development have developed mammary cancer. So measurement of different sex hormones or sex steroids is an essential step during any study related to development and efficacy of treatment of canine mammary cancer.

Depressed immune responses have been observed frequently in cancer patients. Cancer and other stress are known to affect different components of the immune system. Cancer treatment is relying mainly on surgery, anti-cancer chemotherapy and radiation therapy. Most chemotherapeutic agents are responsible to myeloid toxicity, which leads to leukemia and immunosuppression affecting both humoral and cell-mediated immunity. This is a very serious disadvantage of chemotherapy besides they are cytotoxic drugs.

Radiographic examination of mammary tumour patients should be done prior to any treatment to detect the chances of lung metastasis. Radiographs of the thorax helped to provide information pertaining to the extent of organs involved and the presence of metastasis in the lungs. Lateral radiograph of thorax revealed absence of pulmonary metastasis in normal cases. Lung metastasis may observe in animal characterized by radioopaque soft tissue scattered in the lungs indicating pulmonary metastasis.

Cancer, according to current opinion, is a multitude of different diseases and is no more a “one disease’. Myriads of tumour types and plethora of their patho-physiology in different species necessitates species wise study of tumours in detail. Of all species, dog develops neoplasms twice as frequently as humans, with incidence of skin and mammary tumours being the highest. Tumors of mammary gland are the most common tumors of female dog representing approximately 30-50% of all tumors in bitch and it is the second most common tumour in dog after skin neoplasms and most common malignant tumour in dog.

Tumours of mammary gland are the most common tumours of female dog representing approximately 30-50% of all tumours in bitch. Chemotherapy is a kind of treatment that uses drugs to attack cancer cells. The importance of chemotherapy has been emphasized that survival could be prolonged after chemotherapy in cancer patients. Considering immunosuppressive nature of mammary tumours, the use of immunotherapy to prevent cyto-toxicity of cancer drugs, further metastasis and prolong survival period in canines. “ImmuPlus” (Indian Herbs) is a type of polyherbal ayurvedic product containing extracts of Ocimum sanctum, Withania somnifera, Emblica officinale and Tinospora cordifolia.

Tumours of mammary gland are the second most common tumours of female dog representing approximately 30-50% of all tumours. Chemotherapy is a kind of treatment that uses drugs to attack cancer cells. The importance of chemotherapy has been emphasized and reported that survival could be prolonged after chemotherapy in cancer patients. Clinical trials of the combination of selective COX-2 inhibitors with chemotherapy in patients with a number of cancers have been initiated and preliminary results are encouraging. The introduction of immunohistochemistry and newer techniques like nucleolar organizer region (NOR) staining have improved the objective of diagnosis of cancer. Silver stained nucleolar organizer region (AgNOR) count is considered to be valuable prognostic marker for canine malignant lymphomas and other canine tumour. This study is designed to investigate the therapeutic efficacy of chemotherapeutic agent-Methotrexate with or without COX-2 inhibitors-Meloxicam and also to study the potential clinical application of nucleolar organizer regions (NORs) as prognostic indication in canine mammary tumours.

In the modern industrialized world, cancer has become the most feared of all diseases. Cancer has gained considerable relevance in animals now-a-days owing to the increased awareness among people towards animal sufferings and pain. The diagnosis and management of neoplasm, therefore, represent the major challenges faced by a veterinary oncologist. With the emergence of multitude of interdisciplinary and subspecialty fields of cancer science like tumour biology, cancer chemotherapeutics, immuno-pathology etc, different managemental modalities like excisional surgery, chemotherapy and immunotherapy have evolved. These therapies either alone or in combination make all neoplasm patients to have an improved quality and quantity of life if not always cures. The quality of life of the animal should always be prioritized.

Surgery stands as first choice for the treatment of canine mammary tumours. The simplest surgical procedure in the mammary gland should be performed (MacEwen, 1989) in the absence of metastatic disease and inflammatory carcinoma. Nevertheless the controversy for performing simple or radical technique still goes unabated, as the published data are to clear to prove the practical value of radical surgery compared to simple mastectomy. Brodey et al. (1983) is reported that six categories of surgical excision of mammary tumours can be performed.

Cancer is a leading cause of death in both humans and canines. Mammary tumours are most common tumours in canines next to skin tumours. These are common in intact female pertaining to its relation to imbalances in estrogen and progesterone. This study is carried out on 18 client-owned dogs presented to the Institute referral veterinary polyclinics with the history of spontaneous mammary tumours. The animals are randomly divided into three groups viz., groups I, II and III each consisting of six animals.

Canine transmissible venereal tumours (CTVT) is also known as infectious sarcoma, transmissible venereal tumours (TVT), venereal granuloma (VG), canine transmissible venereal sarcoma (CTVS), transmissible lymphosarcoma or Sticker tumour, is a benign reticuloendothelial tumour of the dog that mainly affects the external genitalia and occasionally the internal. As it is usually transmitted during coitus it mainly occurs in young, sexually mature animal. Canine transmissible venereal tumour is histocytic tumours that may be transmitted among dogs through coitus, licking, biting and sniffing tumour affected areas. CTVT is spread by the transfer of living cells between dogs, usually during mating. The tumour cells are themselves the infectious agents, and the tumours that form are not genetically related to the host dog (Purohit, 2008; wikipedia ctvt).

Cancer cryosurgery began in England during 1850s, when James Arnott used local application of salt solutions containing crushed ice to treat advanced cancers in accessible sites, such as breast and the uterine cervix. Since then, landmark advances in chemistry, physics, material science, and biology have culminated in the sophisticated cryosurgical devices currently in use.   Cryosurgery is defined as a method that uses the local application of extreme cold to destroy abnormal or diseased tissue, with the possibility of the maintenance of normal adjacent tissue. Normal tissue can be maintained because the extension of the ice ball can be controlled. Tissue temperature should reach -20o C or below. Attempts should be taken to kill all tissues in the target with minimal damage to surrounding tissues. There is a variable response of tissues to cryotherapy based on density, vascularity and the water content of the tissue, temperature and size of the cryoprobe, spray rate, rate of freeze, rate of thaw and number of freeze and thaw cycles. It is ideal to have quick freeze and slow thaw for maximum benefit. The extent of freezing should be closely monitored, with either temperature monitoring probes or by visual inspection and palpation of frozen area and this is more advantageous in case of relatively small lesions.

References Bhattacharya T K, Rani S, Maiti SK, Dayal S, Kumar P. and Sharma A. (2007) Polymorphism of ZuBeCa3 microsatellite and its association with mammary tumor in dogs. International (European) Journal of Immunogenetics, 34: 161-165. Bassam, J.B., Gustavo, C.A. & Peter M.G. (1991) Fast and sensitive silver staining of DNA in polyacrylamide gel. Analytical Biochemistry, 196: 80. Bostock DE and Owen LN (1972) Chemotherapy of canine and feline neoplasia. Journal of Small Animal Practice, 13: 359-362. Bostock R (1977) Neoplasia of the skin and mammary glands in dogs and cats. In: Kirk, R.W. (ed.): Current veterinary therapy 6: Small Animal Practice. WB Saunders, Philadelphia pp. 493-496. Brodey RS, Gold Schmidt MH and Roszel J R (1983) Canine mammary gland neoplasm. Journal of American Animal Hospital Association, 19: 61-66. Carlson W Dwight (1977) Editor, Carlson’s Veterinary Radiology, Lea and Febiger (3rd Edn). Cooper SM and Dawber RPR (2001) The history of cryosurgery. J R Soc Med. 94:196-201. Cotchin E (1958) Mammary neoplasms of the bitch. Journal of Comparative Pathology, 68: 1. Das AK, Das U, Das BB (1991) Clinical report on the efficacy of chemotherapy in canine transmissible venereal sarcoma. Indian Veterinary Journal, 68:249-252. Daniel A Degner, Mammary Tumours. Vet Surgery Central.Com