Ultrasonographic measurement of the prostatic dimension-to-aortic luminal diameter in healthy intact male dogs and dogs with benign prostatic hyperplasia.

OBJECTIVES: To establish ultrasonographic measurements of the prostatic dimension-to-aortic luminal diameter ratios including the prostatic volume-to-aortic luminal diameter ratio in healthy, intact male dogs and compare these ratios between healthy dogs and dogs affected by benign prostatic hyperplasia. MATERIALS AND METHODS: Healthy dogs (n = 75) and dogs affected by benign prostatic hyperplasia (n = 104) were included in the study. Prostate length, width, average height and aortic luminal diameter were measured from ultrasonographic images. In addition, prostatic volume was calculated, and prostatic volume-to-aortic luminal diameter were also compared. RESULTS: In healthy dogs, aortic luminal diameter was significantly associated with bodyweight and the prostatic width while body condition scores, prostate length and prostatic average height were not associated. Prostatic dimension-to-aortic luminal diameter ratios and prostatic volume-to-aortic luminal diameter ratio was not significantly different among dogs with different body condition scores either in healthy dogs or dogs affected by benign prostatic hyperplasia, except prostatic volume-to-aortic luminal diameter ratio in benign prostatic hyperplasia. Prostatic dimension-to-aortic luminal diameter ratios were significantly higher in benign prostatic hyperplasia while prostatic volume-to-aortic luminal diameter ratio significantly higher in healthy dogs. Prostatic dimension-to-aortic luminal diameter ratios demonstrated medium to high sensitivity and specificity when distinguishing between healthy dogs and dogs affected by benign prostatic hyperplasia. Prostatomegaly, should be considered when the prostatic dimension-to-aortic luminal diameter ratios increase. The calculated cut-off values were 3.68, 4.46 and 3.06 for prostate length-to-aortic luminal diameter, prostatic width- to-aortic luminal diameter and prostatic average height-to-aortic luminal diameter, respectively. CLINICAL SIGNIFICANCE: The prostatic dimension-to-aortic luminal diameter ratios could be useful to evaluate the size of the prostate in dogs, as it is unaffected by the body condition scores.

Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted.

Molecular investigation of the direct anti-tumour effects of nonsteroidal anti-inflammatory drugs in a panel of canine cancer cell lines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as effective adjunctive anti-tumour agents in human and veterinary medicine. However, the molecular mechanisms associated with their anti-tumour effects and correlations with the expression of cyclooxygenase (COX) and related molecules in tumours remain controversial. The objective of this study was to compare the expression profiles of COX and related molecules with NSAID sensitivity and to explore the molecular mechanisms of anti-tumour effects. The expression profiles of COXs, prostaglandins (PGs), PGD2 synthases, and PGE2 synthases were obtained, and their correlations with in vitro sensitivity to the NSAIDs piroxicam, carprofen, and robenacoxib were examined, using 26 canine cancer cell lines. Subsequently, microarray analysis was performed using one melanoma cell line to gain insight into mechanisms by which NSAIDs could exert cytotoxic effects. No strong correlation was observed between the cellular expression of COX and related molecules and sensitivity to NSAID treatment. Additionally, NSAIDs inhibited cell growth only at considerably higher concentrations than those required for functional COX inhibition. Microarray data demonstrated that five genes (SLC16A6, PER2, SLC9A8, HTR2B, and BRAF) were significantly upregulated and that four genes (LOC488305, H2AFJ, LOC476445, and ANKRD43) were significantly downregulated by NSAID exposure to the melanoma cell line. These results suggest that the direct in vitro anti-tumour effects of NSAIDs might be mediated by COX/PG-independent pathways. Novel candidate genes that could potentially be involved in the anti-tumour effects of NSAIDs were identified. Further validation and elucidation of their associated mechanisms will contribute to patient selection in clinical settings and the development of effective combination therapies.

Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma.