Vascular-targeted photodynamic therapy (VTP) of a canine-transmissible venereal tumour in a murine model with Pd-bacteriopheophorbide (WST09)

Treatment of canine‐transmissible venereal tumour (CTVT) with local vascular‐targeted photodynamic therapy (VTP) using Pd‐bacteriopheophorbide (WST09) as a drug is suggested as an alternative to conventional chemotherapy. Male CD1 nude mice were subcutaneously grafted with the xenograft‐transmissible canine venereal tumour (XTVT). The VTP protocol delivered once consisted of intravenous administration of WST09 (10 mg kg^?1) followed by immediate local illumination with a diode laser (763 nm). Controls included animals treated with light or WST09 alone. Macroscopic and microscopic evaluations of tumour response were conducted 10, 24 and 48 h after treatment. Upon VTP, tumours underwent necrosis that lasted 8–10 days and exhibited complete healing by 25–35 days, reaching an overall long‐term cure rate (83%) by 90 days after treatment. This study suggests that VTP with WST09 can efficiently treat CTVT in a single session, as compared with 4–6 sessions of chemotherapy and thus may be feasible for common veterinary practice, particularly under ambulatory conditions.     

Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs?

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL‐6, IFN‐γ, and TGF‐β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN‐γ and IL‐6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF‐β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour‐derived TGF‐β was affecting and even suppressing the real TGF‐β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT’s low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal’s clinical response to treatment.     

Computer tomographic imaging in 4 dogs with primary nasal canine transmissible venereal tumor and differing cellular phenotype

Primary nasal canine transmissible venereal tumor (CTVT) without genital affection is uncommon. The aim of this report was to describe the primary nasal CTVT findings and CT staging in 4 dogs with different cytological phenotypes. Three male dogs and 1 bitch were evaluated for their chronic histories of sneezing, snoring, mucopurulent nasal discharge and nasal deformation. Cytological examination of nasal secretions suggested CTVT, confirmed by histopathological examination and LINE‐1/c‐myc. Males had the plasmacytoid phenotype of CTVT, and the bitch had the lymphocytoid phenotype. CTVT were staged based on the CT findings using modified Adams staging system. The bitch was classified as stage 1, 2 males were classified as stage 3 and 1 male as stage 4. All dogs had a complete tumoral remission after chemotherapy. Plasmacytoid phenotype was identified in cases with most important damage of the nasal cavity. However, the cytological type did not affect the response to chemotherapy.     

The T963C mutation of TP53 gene does not participate in the clonal origin of canine TVT

In dogs, the canine transmissible venereal tumor (CTVT) is the only neoplasm which is not produced by neoplastic transformation of normal cells; the tumor is transmitted from the affected dog to healthy dogs by implantation of one or various clones of cancer cells. Thus, the CTVT of dogs analyzed in various countries reveals similar genetic characteristics and consequently CTVT is considered to have a clonal origin.The CTVTs obtained from dogs in Korea showed the T963C mutation on TP53 gene; this mutation was thought to be a molecular alteration which participates in the origin of the ancestral clone, CTVT. Nonetheless, this supposed mutation has not been identified in other studies which were carried out for the purpose of clarifying the clonal origin of CTVT. Thus we have considered it important to identify the role of the T963C mutation of the TP53 gene in the clonal origin of CTVT in dogs.Consequently the region which includes the mutation of the TP53 gene in twenty samples of CTVT obtained from various canine breeds was PCR amplified and afterwards its sequence of nucleotides was determined. We conclude that this mutation did not participate in the clonal origin of the tumor, but was acquired at a later stage.