Efficacy of mitoxantrone against various neoplasms in dogs

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.     

Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms

Melanomas diagnosed in 29 cats over an 11 year period included 19 ocular (16 intraocular, three palpebral), five oral, and five dermal melanomas. Intraocular melanomas involved the ciliary body and iris in 12; the whole eye was involved in four. The average age of cats with intraocular melanomas was 11 years; the female : male ratio was 9 : 7. Histologically, eight intraocular tumors were mixed, six were epithelioid, and two were spindle cell. Ten of 16 cats (62.5%) with intraocular melanomas were killed because of the tumor at a mean of 156 days; four are living with no evidence of disease (average, 255 days). The mean time of death in cats with palpebral melanoma was 409 days. Metastasis occurred in 63% of cats with intraocular melanoma and all cats with palpebral melanoma. Four cats with oral melanoma were killed at a mean of 61 days; all had metastasis. Of five cats with cutaneous melanoma, one was killed with metastasis at 90 days; three cats were alive without evidence of recurrence or metastasis greater than 365 days after surgery. Results of this study indicate that in the cat, ocular melanomas are more common than oral and dermal melanomas, and ocular and oral melanomas are more malignant than dermal melanomas, with higher rates of mortality and metastasis.     

Use of fenbendazole suspension (10%) against experimental infections of Toxocara canis and Ancylostoma caninum in beagle pups

Eleven nematode-free Beagle pups were inoculated with Ancylostoma caninum and Toxocara canis; infection became patent 13 and 35 days later, respectively. Eight pups were treated with fenbendazole oral suspension (10%) at a dosage of 50 mg/kg of body weight/day for 3 days. The remaining three animals were unmedicated controls. The drug was effective in reducing both ascarid and hookworm burdens, and there was marked improvement in the clinical condition of treated pups as compared with unmedicated control pups. Natural expulsion of worms in control animals was 53% for ascarids and 2% for hookworms. Drug-related toxicosis was not observed in any of the medicated animals. It was concluded that fenbendazole oral suspension (10%) at the 50-mg/kg dosage is easily administered and is an effective drug for reducing nematode burdens in experimentally infected pups.     

Results of a survey of small-animal practitioners on the perceived clinical efficacy and safety of an oral nutraceutical

A mail survey of 3080 practitioners from two sampling frames was used to determine the perceived clinical efficacy and safety of an oral nutraceutical for the treatment of degenerative joint disease (DJD) in small animals. Overall response rate was 82%, of which 64% reported that they were recommending the oral nutraceutical to their clients. There was a high variability reported between the severity of DJD and response to treatment. Sixty-eight percent of practitioners reported lame dogs older than five years to be the most responsive to treatment. Most practitioners (83%) believed response to treatment with the studied product occurred within four weeks. Practitioners using the product rated the clinical efficacy of the product to be either 'good' or 'excellent' in improving mobility, alleviating pain and improving attitude in the majority of the treated animals. No practitioner reported a worsening of pain, mobility or attitude. Self-reported adverse effects were 2% (the most common was gastrointestinal upset). The results of this survey indicated that perceived clinical efficacy of the studied nutraceutical in the treatment of DJD was regarded to be 'good' or 'excellent' by most of the practitioners who use this product and was considered to be safe with minimal side effects. This provides additional information on the product for use in planning future clinical trials.     

Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats

This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.     

Induction of systemic and mucosal immune response in cattle by intranasal administration of pig serum albumin in alginate microparticles

Biodegradable microparticles are an efficient mucosal delivery system that protect antigens from the harsh mucosal environment and facilitate their uptake by M cells at the epithelium of mucosal-associated lymphoid tissue. In this study, we determined the systemic and mucosal immune response in calves following intranasal and oral immunization with pig serum albumin (PSA) encapsulated in alginate microparticles. The size of the particles ranged from 1 to 50 microm in diameter, with 95% of the particles being smaller than 5 microm. High levels of anti-PSA IgG1 antibodies were found in the serum, nasal secretions, and to a less extent in saliva of calves vaccinated intranasally, but not orally, with PSA-microparticles. There was no significant increase of PSA-specific IgA. A weak lymphocyte proliferative immune response was observed in peripheral blood mononuclear cells (PBMCs), and few anti-PSA antibody-secreting cells (ASC) were detected in the blood of calves immunized intranasally. The combined systemic and mucosal response observed in intranasally immunized animals may be attributed to the wide variation in the size of the alginate microparticles, with smaller particles translocating to regional lymph nodes and inducing a systemic immune response, and larger particles being retained in the NALT and inducing a mucosal immune response. The procedure presented here may be useful as an intranasal vaccine against respiratory diseases in cattle.     

Dose-titration studies of ivermectin against experimental Ancylostoma caninum and Uncinaria stenocephala infections

Dose-titration trials of ivermectin were conducted on pups with dual experimental infections of 4th-stage larvae or adult Ancylostoma caninum and Uncinaria stenocephala. Ivermectin was administered orally or subcutaneously at dosages of 0.006, 0.012, or 0.024 mg/kg of body weight. Maximal or near maximal (greater than or equal to 96% to 100%) anthelmintic effect was observed for both stages of development for each hookworm species by either route of administration at a dosage of 0.024 mg/kg. Responses for all of the aforementioned categories were linearly related to increasing log dosage of ivermectin, with common slopes (regression coefficients). Regression analysis also provided estimates of the minimal dosages required to produce maximal reduction in worm burden for each stage, species, and route of administration. The estimated ivermectin dosages for maximal efficacy ranged from a low of 0.014 mg/kg for adult A caninum by oral treatment to 0.044 mg/kg for 4th-stage larvae of U stenocephala by oral treatment.     

Treatment of Metastatic Equine Melanoma with a Plasmid DNA Vaccine Encoding Streptococcus Pyogenes EMM55 Protein

A 19-year-old castrated male Arab/Quarter horse presented with an extensive history of cutaneous metastatic melanoma. Over a period of 8 months, a total of 8 doses of plasmid DNA vaccine expressing the Streptococcus pyogenes emm55 gene (pAc/emm55) were administered intratumorally at 300 μg/dose via a needless injector. Upon completion of the vaccination protocol, the size of the injected lesions, on average, were reduced by 40.3% from the initial size measurements. Lesions that were not injected were reduced by 47.6%. The overall reduction in total tumor burden was 42.3%. Tumor regression was also associated with the augmentation of antimelanoma IgG antibody response, thus implying that an induction of an effective antimelanoma response would be of great advantage in the management of equine melanoma.     

A RETROSPECTIVE ANALYSIS OF 140 DOGS WITH ORAL MELANOMA TREATED WITH EXTERNAL BEAM RADIATION

Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy x 4 fractions; 30 Gy, 10 Gy x 3 fractions; or >45 Gy, 2-4 Gy x 12-19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4-6 months) and the median survival was 7.0 months (95% C.I., 6-9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p < .001, p < .001, and p = .04, respectively) and survival (p < .001, p < .001, and p = .05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.     

Melan A and S100 protein immunohistochemistry in feline melanomas: 48 cases

Immunohistochemistry, using a monoclonal antibody to Melan A and a polyclonal antibody to S100 protein, was applied to 48 formalin-fixed, paraffin-embedded specimens of feline melanoma. Forty-two cutaneous, three oral, one mucocutaneous, and two metastatic melanomas comprised the tumors. Thirty-two tumors (67%) were positive for Melan A and 42 (87.5%) were positive for S100. All but one of the tumors that were positive for Melan A were also positive for S100. S100 was detected in 11 of 16 tumors that were negative for Melan A. Seventy-five percent (9 of 12) of amelanotic melanomas were negative for Melan A. Normal adrenal cortex, the cerebellum, and the skin had cells that were positive for Melan A. Sebaceous adenoma was the only nonmelanocytic tumor examined that reacted with antibody to Melan A. Although less sensitive than S100 protein, Melan A is more specific for melanoma and is useful in differentiating feline cutaneous melanoma from the more common pigmented basal cell tumor.     

Reirradiation of tumors in cats and dogs

Fifty-one cats and dogs with tumor recurrence after irradiation were treated with a second course of radiotherapy, using either teletherapy or brachytherapy. Eighty-six percent of the tumors had partial or complete response at 2 months after reirradiation. Tumor response was significantly (P = 0.041) affected when the interval between the 2 courses of irradiation was greater than 5 months. The estimated local tumor control rate was 38% at 1 year after reirradiation. Of all the factors examined, complete response at 2 months, reirradiation field size less than or equal to 10 cm2, and reirradiation dose greater than 40 gray emerged as predictors of local tumor control. The estimated overall survival rate was 47% at 2 years. Tumor location had a significant (P = 0.001) influence on overall survival; animals with cutaneous tumors had the longest survival times, and those with oral tumors had the shortest survival times. The other significant (P = 0.001) factor affecting overall survival time was the field size of the reirradiated site. Estimated survival time after reirradiation was 41% at 1 year. Favorable prognostic indicators were complete response at 2 months and location of tumor; animals with skin tumors had a favorable prognosis. The acute effects of reirradiation on normal tissues were acceptable, but 12% of the animals had severe delayed complications. Significant risk of complications after reirradiation was associated with squamous cell carcinoma (P = 0.015) and reirradiated field size greater than 30 cm2 (P = 0.056). When the interval between irradiations was greater than 5 months, the risk of complications was significantly (P = 0.022) lower.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's-like syndrome) in a cat

A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sj?gren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.     

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow‐up of 6 months. Epidemiological, clinical and histological data were collected and quantitative‐PCR were performed on formalin‐fixed paraffin‐embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.     

Oral vitamin A as an adjunct treatment for canine sebaceous adenitis

Medical records of dogs with sebaceous adenitis diagnosed by histopathology over an 18-year period were reviewed. From a total of 40 cases, 24 were treated with oral vitamin A. Dogs ranged from 9 months to 12 years of age at the time of disease onset. Purebred as well as mixed-breed dogs were affected. Akitas represented approximately one-third of the affected population. No sex predilections were observed. Vitamin A was administered for a minimum of 1 month. Doses varied from 380 to 2667 IU/kg/day, with a mean of 1037 IU/kg/day. Two dogs received oral vitamin A exclusively. Concurrent treatments included systemic antibiotics, systemic antifungal medications, fatty acid supplementation and various topical treatments. Of 24 dogs treated with vitamin A, three were lost to follow-up. Twelve owners were satisfied with the overall appearance of their dogs, reporting ≥25% improvement in clinical signs, including level of pruritus, amount of scale, alopecia and overall coat quality, compared with pretreatment appearance. Three owners observed adequate initial improvement, with regression to pretreatment state within 6 months of starting treatment. Two owners reported 25-50% improvement in clinical signs while on oral vitamin A supplementation; however, changes were attributed to concurrent topical treatment. Six owners reported no improvement and discontinued oral administration of vitamin A within 7 months. No correlations could be made between vitamin A dosage and response to treatment; prognoses could not be made based on clinical and histopathological findings.     

Antitumour effects of Liporaxel (oral paclitaxel) for canine melanoma in a mouse xenograft model

Paclitaxel, a member of the taxane family, exhibits antitumour effects by targeting the microtubules in cancer cells. Recently, oral paclitaxel has been developed to overcome the side effects of intravenous paclitaxel administration in human patients. The objective of this study was to investigate the antitumour effects of oral paclitaxel in vitro and in vivo. Three weeks after inoculation, oral paclitaxel (25 and 50 mg/kg) or saline was administered every week for three consecutive weeks. To explore the underlying mechanism, tumour angiogenesis was examined by immunohistochemistry with an anti‐CD31 antibody. Tumour cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick‐End Labeling assay, and cell cycle arrest was confirmed by western blot analysis. Oral paclitaxel treatment of canine melanoma cells exerted mediated antiproliferative effects and mediated cell cycle arrest in vitro. In animal experiments, after oral paclitaxel administration, the average tumour size decreased to approximately 30% of that in the control. Histologically, oral paclitaxel showed anti‐angiogenic effects and induced the apoptosis in tumour tissues. Oral paclitaxel also downregulated the intratumoural expression of cyclin D1 and inhibited cell proliferation. The study findings support potential application of oral paclitaxel as a novel chemotherapeutic strategy to treat canine melanoma. This is the first study to investigate the potential of oral paclitaxel as a therapeutic drug against canine tumours.     

Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha) interferon on feline herpesvirus replication

The antiviral activities of 9-(2-hydroxyethoxymethyl)guanine (acyclovir; ACV) either alone or combined with recombinant human leukocyte (alpha) A/D interferon (rHuIFN-alpha) against feline herpesvirus type 1 (FHV-1) were evaluated in feline embryo cell cultures, using an infectivity-inhibition assay. In ACV-treated cultures, the 50% inhibitory dose (ID50) was approximately 10 to 20 micrograms of ACV/ml. Maximal inhibition of FHV-1 infectivity (range, 3.4 to 4.2 log10 TCID50) was observed when high test doses of ACV (125 or 250 micrograms/ml) were given 1 to 6 hours after infection. Although mild inhibition (range, 0.3 to 1.6 log10 TCID50) of virus was observed at lower drug doses (10 to 62.5 micrograms/ml), FHV-1 was relatively resistant to ACV and required higher minimal inhibitory doses than those reported for other herpesviruses. However, when ACV was combined with 10 or 100 U of rHuIFN-alpha/ml, synergistic antiviral effects were associated with ACV dosage of 10 to 62.5 micrograms/ml. Antiviral activities resulting from use of the combined drugs permitted nearly eightfold reduction in the dose of ACV required to achieve maximal inhibition of FHV-1. Significant (P less than 0.01) synergistic interactions with ACV resulted when the rHuIFN-alpha was given before or after infection; at the lower doses of ACV, however, rHuIFN-alpha pretreatment was more effective. Although dosages of either greater than or equal to 62.5 micrograms of ACV/ml or 100 U of rHuIFN-alpha/ml were cytosuppressive in control cell cultures, additive anticellular effects were not observed at synergistic combinations of ACV and 10 U of rHuIFN-alpha/ml.     

Bovine papular stomatitis, first report of the disease in Mexico

In a herd of 120 two to eight months old calves kept at a Mexican Government experimental station in Ajuchitlan, Querétaro, weight loss and ptialism were observed. Upon a clinical examination, it was found that 31 (25.8%) of the animals disclosed papules in the oral and perioral regions. Biopsies from the affected tissues were studied with the light and electron microscopes. Serological studies and isolation of the virus were also carried out. A Pox virus was identified (240 x 100 x 150 +/- 7% nm) with the electron microscope. Dermatophilus sp. was occasionally observed. Bovine kidney monolayers, inoculated with affected bovine tissues demonstrated cytopathic effect up to the 4th serial passage. Inoculation with cell cultured infectious material in the oral submucosa (cell lysate) produced typical lesions of BPS on a heifer. Infectious tissues from this experimentally inoculated animal produced cytopathic effect in tissue cultured cells after 24 hours, and this last material was infectious for a second young heifer. Virus-neutralization tests, using an hyperimmune serum, disclosed a neutralization index of 1.5 logarithms. It was concluded that bovine papular stomatitis virus was the etiological agent.     

The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine

As a result of its metastatic potential, canine malignant melanoma like its human counterpart like its human counter part, has a poor response to conventional treatment protocols. This prompted us to investigate the possibility of enhancing the immune response against the melanoma cell surface antigen, disialoganglioside GD3. Initially a flow cytometric study was designed in which the incidence of GD3 on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was established in canine melanoma cell lines. Results from the flow cytometry found GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell lines. Since it was thus potentially a good target, a study in which normal dogs were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2 phosphate buffered saline. Caliper measurements were collected to assess skin reaction at the vaccination site and sera assayed for IgM and IgG antibodies against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results from the study found significant differences (P<0.05) in the vaccine site reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3 concentration in the vaccine increased the inflammation response at the injection site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over time and achieved significance at weeks 9 and 12, respectively. Cell-mediated cytotoxicity was only detected in peripheral blood mononuclear cells from vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak self-antigen) and an adjuvant, tolerance was overcome by an innate and adaptive immune response in this population of normal dogs.     

Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines

Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 μM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 μM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G₁-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma.