Veterinary Comparative Oncology

This report describes a 16-month-old female, otherwise seemingly healthy, Siberian husky dog with severe oral papillomatosis that did not regress spontaneously and was refractory to surgical treatment over a 6-month period. Regression of the papillomas was achieved by administering a series of experimental vaccinations starting at the time of the last surgery. The vaccine consisted of systemically administered canine oral papillomavirus major coat protein L1 that has been shown to self-assemble into virus-like particles. They cause a humoral response that has been shown to prevent the onset and development of papillomas. In this case, however, following unsuccessful surgical treatment, the vaccine acted therapeutically, causing the papillomas that had regrown to shrink. No side-effects were noted.

Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL-DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148-184]. The 1/ 2 year and one-year survival was 41.2% (95% CI 24.8-56.9) and 22.7% (95% CI 9.9-37.4), respectively. In dogs treated with PL-DOX, a desquamating dermatitis like palmar-plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups.

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome. recognized that a subset of patients would go into durable remissions (i.e. be cured); however, despite a high initial response rate (higher than 80% in most protocols), the majority of dogs would relapse and succumb to their lymphoma. Only 20-25% of the cases would be alive for 2 years or longer. The high response rates to relatively low dose-intense protocols indicate that canine lymphomas are uniquely chemotherapy sensitive tumours, and also suggest that further improvements, both in terms of remission rates and survival times, may be made through dose intensification. Results from human oncology trials, however, have been mixed; some studies have documented clinically significant improvements in outcome in patients treated with such doseintense/dose-dense protocols, whereas others have resulted in only marginal or no improvements in remission and survival durations. 21 -26 The inconsistent results from dose intensification may in part be due to the presence of cancer stem cells, a distinct

The safety and effi cacy of intra-incisional 5-fl uorouracil (5-FU) in the management of incompletely resected malignant spindle cell tumours of extremities was evaluated in six dogs. After marginal surgery, the dogs underwent weekly intra-incisional 5-FU for a minimum of six cycles. Treatment was well tolerated by all dogs, with no systemic adverse effects and only one episode of local cutaneous hyperpigmentation, which completely and spontaneously resolved. Median follow-up for all the dogs was 546 days (mean 619; range 297 -1207). At the date of analysis, four dogs were still alive with no evidence of local recurrence, and two dogs had died as a result of their disease. The cause of death was development of distant metastases in one dog and tumour regrowth in the other. Despite the small sample size, this study documents that intra-incisional 5-FU chemotherapy is a safe and effi cacious adjuvant treatment in the case of incompletely resected malignant spindle cell tumours in dogs and that long disease control can be achieved.

Mammary tumours represent the most common neoplastic disease of the female dog, and the incidence in female dogs is much higher than in women. Whereas the influence of sexual steroids on breast cancer (BC) development in dogs has been studied, very little is known about the role of prolactin (PRL). New studies show that until recently, the importance of PRL in human BC development and progression has been highly underestimated. PRL plays a role in promoting benign as well as malignant neoplastic cell growth in BC in vitro and in vivo. Sporadic publications proposed a tumour promotor role in the dog. The goal of this review is to summarize our knowledge about PRL and human BC as well as canine mammary tumourigenesis, and propose future research in this area.

Aim: Recent trends in comparative animal and human research inform us that collaborative research plays a key role in deciphering and solving cancer challenges. Globally, cancer is a devastating diagnosis with an increasing burden in both humans and dogs and ranks as the number three killer among humans in Kenya. This study aimed to provide comparative information on cancers affecting humans and dogs in Nairobi, Kenya. Materials and Methods: Dog data collection was by cancer case finding from five veterinary clinics and two diagnostic laboratories, whereas the human dataset was from the Nairobi Cancer Registry covering the period 2002-2012. The analysis was achieved using IBM SPSS Statistics ® v.20 (Dog data) and CanReg5 (human data). The human population was estimated from the Kenya National Census, whereas the dog population was estimated from the human using a human:dog ratio of 4.1:1. Results: A total of 15,558 human and 367 dog cancer cases were identified. In humans, females had higher cancer cases 8993 (an age-standardized rate of 179.3 per 100,000) compared to 6565 in males (122.1 per 100,000). This order was reversed in dogs where males had higher cases 198 (14.9 per 100,000) compared to 169 (17.5 per 100,000) in females. The incident cancer cases increased over the 11-year study period in both species. Common cancers affecting both humans and dogs were: Prostate (30.4, 0.8), the respiratory tract (8.3, 1.3), lymphoma (5.6, 1.4), and liver and biliary tract (6.3, 0.5), whereas, in females, they were: Breast (44.5, 3.6), lip, oral cavity, and pharynx (8.8, 0.6), liver and biliary tract (6.5, 1.2), and lymphoma (6.0, 0.6), respectively, per 100,000. Conclusion: The commonality of some of the cancers in both humans and dogs fortifies that it may be possible to use dogs as models and sentinels in studying human cancers in Kenya and Africa. We further infer that developing joint animal-human cancer registries and integrated cancer surveillance systems may lead to accelerated detection of the risks of cancer in Africa.

Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials.

Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clini...

The immunological biomarkers profiles were evaluated using Luminex as putative measures to monitor canine mammary carcinomas (MCs). Forty female dogs were categorized into benign mixed tumour (MC-BMT = 28) and mammary carcinoma (MC=12). The ascendant biomarker signatures were used to compare the groups. For example, a higher frequency of MC-BMT animals producing IL-6, CXCL-8 and CXCL-10 was observed, whereas for the MC group IL-2 and CXCL-8 were detected. MC-BMT animals without metastasis had an increase in the levels of IL-2, CXCL-8, CXCL-10, IL-6, TNF-α, IL-15 and a decrease in IL-10 and CXCL-8. MC-BMT animals with metastasis showed only an increase in CXCL-10 and a decrease in IL-18. After comparing the ascendant signatures following the presence of metastasis in both groups, a higher frequency of dogs exhibiting IL-10 production was observed. Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC) curve analysis revealed that this pattern was associated with...

In this retrospective study, the efficacy and safety were examined for an intraperitoneal chemotherapy protocol-cyclophosphamide, vincristine and prednisolone (IP-COP) in 26 cats with malignant lymphoma. Certainly in cats fiercely resisting IV administration the IP route is a more practical method, safer for the administrator and less stressful for the cat. Complete remission (CR) rate was 76.9% (n = 20). Median duration of first remission was 421 days. Estimated 1-and 2-year disease free period were 67.1 and 48.0%, respectively. Median duration of survival was 388 days and estimated overall 1-and 2-year survival periods were 54.7 and 46.9% respectively. Young cats had a more favourable prognosis. Reaching CR was essential for long-term survival. No specific IP-related adverse events (AE) were seen. AE were generally scored as mild and were not excessively abundant. These results indicate that the IP route is a safe and effective alternative for the administration of COP protocol chemotherapeutics.