Glycoproteomic profiling of serum peptides in canine lymphoma and transitional cell carcinoma

Differential expression of fucosylated glycoproteins has been correlated with malignancy and metastatic potential in various types of neoplasia. Utilizing glycoproteomics techniques, changes in fucosylated serum peptides associated with naturally occurring canine lymphoma and transitional cell carcinoma (TCC) have been evaluated. In both types of neoplasia, the majority of the fucosylated peptides that changed increased with the cancer. In one lymphoma case that was examined over the course of the disease, the same fucosylated peptides that increased during pre-chemotherapy decreased during post-chemotherapy, and then subsequently increased upon recurrence of the lymphoma. When comparing all the fucosylated peptides that increased in both types of cancer, there were only two peptides in common allowing discrimination between lymphoma and TCC based on their peptide profiles. These results emphasize the prospect of glycopeptide profiling in proteomics for use in discovering a panel of non-invasive, diagnostic or prognostic biomarkers of cancer.     

Predicting clinical outcome in feline oral squamous cell carcinoma: tumour initiating cells,telomeres and telomerase

Feline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi‐1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi‐1 expression, supporting the predictive value of Bmi‐1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi‐1, Ki67 and EGFR. Taken together, our results imply that Bmi‐1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition – in combination with SRT – would be expected to have beneficial treatment outcome.     

Environmental risk factors for the development of oral squamous cell carcinoma in cats

BackgroundRisk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear.ObjectivesTo investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases.AnimalsHundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls.MethodsProspective, observational case‐control study. Cats with OSCC were compared with an age‐matched control sample of client‐owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information.ResultsOn multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03‐3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07‐2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05‐3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04‐3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor.Conclusions and Clinical ImportanceThe study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age‐matched controls, OSCC shared several risk factors with CGS and PD.     

Treatment of oral squamous cell carcinoma in a horse by surgical debulking followed by metronomic chemotherapy

A 19‐year‐old Quarter Horse gelding presented with a 6‐week history of hypersalivation, halitosis and dysmasesis. Oral examination revealed retention of food and saliva and the presence of a raised, nodular, 6 × 7 cm, ulcerated mass on the dorsal surface of the tongue base. The mass was confirmed histologically as squamous cell carcinoma. Complete resection of the mass was not possible and surgical laser debulking was followed 15 days later by chemotherapy with a combination of meloxicam and cyclophosphamide in metronomic regimen. After one week, there was a significant improvement in clinical signs and food consumption returned to normal. Therapy was well tolerated with no alteration in haematological or urinalysis parameters. After 5 months of excellent life quality, the horse showed progressive difficulties in mastication and swallowing. Endoscopic examination showed extension of the tumour to all the aboral aspect of the tongue and, with the owner's consent, the patient was subjected to euthanasia. This is believed to be the first report on the combined use of meloxicam and cyclophosphamide in a metronomic fashion for management of an oral squamous cell carcinoma in a horse. Since metronomic therapy is less expensive than conventional chemotherapy, easily administrable and well tolerated, it should be considered as a possible treatment option for nonresectable equine malignant tumours.     

Clinical features and outcome of dermal squamous cell carcinoma in 193 dogs (1987‐2017)

Squamous cell carcinoma (SCC) is a frequently recognized dermal tumour in dogs and has been described as a common pathology induced by solar ultraviolet radiation exposure. Little has been published about this neoplasm with regard to clinical features and outcome in dogs. This retrospective study included 193 dogs from a single institution histopathologically diagnosed with SCC of the dermis. Thirty‐eight percent of all dogs had documented histopathologic actinic change. The overall median survival time was 1004 days, with the population demonstrating actinic change associated with a significantly longer survival time (median 1359 days, range 16‐3530 days) compared to dogs without actinic change (median 680 days, range 16‐3066 days) and this achieved significance on multivariate analysis (hazard ratio 0.42, 95% confidence interval 0.193‐0.930, P = 0.032). These data demonstrate increased survival of dogs with SCC demonstrating actinic change over those with non‐actinic SCCs, and purports long‐term survival for these animals. Dogs received a variety of treatment approaches as a retrospective study, and future prospective studies will be necessary to investigate whether adjunct therapies such as radiation or chemotherapy offer improvement in survival for dermal SCC in the dog.     

Electrochemotherapy in treatment of canine oral non‐tonsillar squamous cell carcinoma. A case series report

Non‐tonsillar squamous cell carcinoma (ntSCC) is a common and locally aggressive oral tumour in dogs. The treatments of choice are currently surgery and radiotherapy. Electrochemotherapy (ECT) is a local ablative anti‐tumour technique using electric pulses to enhance the intracellular diffusion of cytotoxic drugs. The aim was to retrospectively evaluate the outcome of patients with oral ntSCC treated with ECT. Twelve dogs with ntSCC were retrospectively enrolled. ECT was combined with IV bleomycin (15 000 UI/m²) alone in 11 cases and post‐surgery in 1. Parameters considered were: tumour site and size, electroporation parameters, response rate (complete remission [CR], partial remission [PR]), median survival time (MST), recurrence rate (RR), median disease‐free interval (DFI) and treatment toxicity (6‐point scale). Median tumour size was 1.65 cm (range 0.3‐8.0 cm) and the response rate was 90.9% (10/11; 8 CR and 2 PR). Two dogs underwent a second ECT. MST for dogs dead with tumour (n = 2) was 110 days and for dogs dead without tumour (n = 3) was 831 days. Among five surviving dogs, one experienced tumour recurrence and four were in CR. Results from two dogs were analysed separately. Overall RR was 27.3%. DFI and MST for dogs with recurrence were 50 and 115 days, respectively. Treatment toxicity was very low. We noticed that all dogs with tumours smaller than 1‐2 cm achieved CR without recurrence suggesting a favourable prognosis when using ECT. ECT for canine ntSCC could be considered a valid treatment option especially for smaller tumours, but a larger caseload would be needed to confirm this statement.     

Intralesional 5‐fluorouracil (5‐FU) for the treatment of eyelid squamous cell carcinoma in 5 horses

Eyelid squamous cell carcinoma in equine patients often presents a therapeutic challenge to practitioners due to the generally large area affected upon presentation. Surgical excision can be curative if wide enough margins are achieved, but this is not often attainable without enucleation. Other alternatives have been examined including cryotherapy, radiotherapy, brachytherapy, intralesional chemotherapy and photodynamic therapy. Intralesional chemotherapy using cisplatin, mitomycin‐C and bleomycin have been shown to be successful in treating eyelid squamous cell carcinomas but may be prohibitive to some owners due to the cost of therapy. To the authors' knowledge, this is the first case series to illustrate the effectiveness of intralesional 5‐fluoruracil in treating large equine eyelid squamous cell carcinomas. Macroscopic reduction in the size of the affected areas was noted in each case together with regression of clinical signs associated with the mass. This, coupled with the relative inexpensive nature of the procedure, makes this technique an attractive therapy for either primary treatment of eyelid squamous cell carcinoma or as a cytoreductive technique prior to surgical excision.     

Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: a pilot study

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.     

Use of imiquimod 5% cream (Aldara™) in cats with multicentric squamous cell carcinoma in situ: 12 cases (2002–2005)*

Multicentric squamous cell carcinoma in situ (MSCCIS) is a variant of squamous cell carcinoma in cats, commonly referred to as Bowen’s‐like disease. Imiquimod 5% cream (Aldara?) is a novel immune response modifier (IRM) that has been reported as a successful treatment for Bowen’s disease in humans. The purpose of this study was to describe clinical findings, treatment protocols and survival in cats with MSCCIS treated with imiquimod 5% cream and to examine the effects of imiquimod 5% cream in cats with MSCCIS. The expression of papillomavirus group‐specific antigen in the study population was also determined. From review of medical records, 12 cats were identified with a histologic diagnosis of MSCCIS and treatment with imiquimod 5% cream. Initial lesions responded to imiquimod 5% cream in all cats. Most cats (75%) developed new lesions. New lesions also responded to imiquimod 5% cream in all cats treated. Five cats (41%) had side effects suspected to be associated with the use of imiquimod 5% cream, including local erythema (25%), increased liver enzymes and neutropenia (8%), and partial anorexia and vomiting (8%). Kaplan–Meier median treatment duration and median survival time probabilities for cats in this study were 1189 days, respectively. A time to failure model was generated as many cats were censored from analysis well before the aforementioned projected median. This model resulted in a shorter median survival time of 243 days. No patient‐related, tumour‐related or treatment‐related prognostic variables were identified. No expression for papilloma group‐specific antigen was found. Imiquimod 5% cream appears to be well tolerated in the majority of cats, and further studies are warranted to further examine its usefulness in cats with this disease.