Massive uterine lipoleiomyoma and leiomyoma in a miniature poodle bitch.

A 15-year-old, intact, female miniature poodle was presented for further evaluation of a large abdominal mass. Computed tomography was conducted to determine the origin of the mass and 2 large uterine masses were discovered. Ovariohysterectomy was performed and histopathological evaluation revealed a massive uterine lipoleiomyoma (27 × 17 × 15 cm), the largest recorded in the veterinary literature, and a smaller leiomyoma (7 × 5 × 4 cm).

Lipoléiomyome utérin massif et léiomyome chez une chienne Caniche miniature. Une chienne Caniche miniature intacte âgée de 15 ans a été présentée pour une évaluation approfondie d'une grosse masse abdominale. Une analyse par tomodensitométrie a été réalisée afin de déterminer l'origine de la masse et deux grandes masses utérines ont été découvertes. L'ovariohystérectomie a été réalisée et l'évaluation histopathologique a révélé un lipoléimomyome utérin massif (27 × 17 × 15 cm), le plus gros jamais consigné dans la littérature vétérinaire et un plus petit léiomyome (7 × 5 × 4 cm).(Traduit par Isabelle Vallières).

The impact of pamidronate and chemotherapy on survival times in dogs with appendicular primary bone tumors treated with palliative radiation therapy.

OBJECTIVE: To assess survival times in dogs that received palliative radiation therapy (RT) alone, and in combination with chemotherapy, pamidronate, or both for primary appendicular bone tumors and determine whether the addition of these adjunctive therapies affects survival. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 50) with primary appendicular bone tumors. METHODS: Dogs were divided into the following treatment groups: RT alone, RT + chemotherapy, RT+ pamidronate, and RT+ chemotherapy + pamidronate. Dogs were considered for analysis if they had a known euthanasia date or follow-up data were available for at least 120 days from the time of diagnosis. Survival time was defined as the time from admission to euthanasia. Cox proportional hazard models and Kaplan-Meier survival functions were used. A P value of less than .05 was considered significant. RESULTS: Fifty dogs were considered for survival analysis. Median survival times (MSTs) were longest for dogs receiving RT and chemotherapy (307 days; 95% CI: 279, 831) and shortest in dogs receiving RT and pamidronate (69 days; 95% CI: 47, 112 days). The difference in MST between dogs who received pamidronate and those who did not in this population was statistically significant in a univariate (P = .039) and multivariate analysis (P = .0015). The addition of chemotherapy into any protocol improved survival (P < .001). CONCLUSIONS: Chemotherapy should be recommended in addition to a palliative RT protocol to improve survival of dogs with primary appendicular bone tumors. When combined with RT ± chemotherapy, pamidronate decreased MST and should not be included in a standard protocol.

VEGFR2 expression and TGF-ß signaling in initial and recurrent high-grade human glioma.

OBJECTIVE: Bevacizumab has promising activity against glioma, although reasons for poor efficacy and variable response rates in certain patients are unclear. Vascular endothelial growth factor receptor 2 (VEGFR2) is heterogeneously expressed within the microvasculature of various malignancies. Moreover, transforming growth factor ß (TGF-ß), a negative prognostic factor for glioma, is intimately involved in angiogenesis including VEGFR2 regulation. Our objective was to associate expression of VEGFR2 and TGF-ß activity with clinicopathological features of human glioma. METHODS: Expression patterns determined by immunohistochemistry for VEGFR2 and phosphorylated Smad2 in human gliomas were compared to overall survival, progression-free survival (PFS), initial versus recurrent tumors and tumor grade. RESULTS: Endothelial VEGFR2 expression was low or undetectable in normal tissue but the proportion of VEGFR2-positive vessels increased with tumor grade. Decreased PFS was associated with tumors whose vessels had increased proportions of VEGFR2 at recurrence. Neither parenchymal nor endothelial cell p-Smad2 was associated with tumor grade; however, the former was negatively correlated with overall survival in glioblastoma multiforme. CONCLUSIONS: The molecular phenotype of the vasculature based on the status of VEGFR2 but not p-Smad2 is related to aspects of glioma progression and patient response. Changes in VEGFR2-positive vessels may account for variable therapeutic efficacy of anti-angiogenic agents.

VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment.

BACKGROUND: Targeting tumor vasculature is a strategy with great promise in the treatment of many cancers. However, anti-angiogenic reagents that target VEGF/VEGFR2 signaling have met with variable results clinically. Among the possible reasons for this may be heterogeneous expression of the target protein. METHODS: Double immunofluorescent staining was performed on formalin-fixed paraffin embedded sections of treated and control SW480 (colorectal) and WM239 (melanoma) xenografts, and tissue microarrays of human colorectal carcinoma and melanoma. Xenografts were developed using RAG1-/- mice by injection with WM239 or SW480 cells and mice were treated with 20 mg/kg/day of cyclophosphamide in their drinking water for up to 18 days. Treated and control tissues were characterized by double immunofluorescence using the mural cell marker α-SMA and CD31, while the ratio of desmin/CD31 was also determined by western blot. Hypoxia in treated and control tissues were quantified using both western blotting for HIF-1α and immunohistochemistry of CA-IX. RESULTS: VEGFR2 is heterogeneously expressed in tumor vasculature in both malignant melanoma and colorectal carcinoma. We observed a significant decrease in microvascular density (MVD) in response to low dose metronomic cyclophosphamide chemotherapy in both malignant melanoma (with higher proportion VEGFR2 positive blood vessels; 93%) and colorectal carcinoma (with lower proportion VEGFR2 positive blood vessels; 60%) xenografts. This reduction in MVD occurred in the absence of a significant anti-tumor effect. We also observed less hypoxia in treated melanoma xenografts, despite successful anti-angiogenic blockade, but no change in hypoxia of colorectal xenografts, suggesting that decreases in tumor hypoxia reflect a complex relationship with vascular density. Based on α-SMA staining and the ratio of desmin to CD31 expression as markers of tumor blood vessel functionality, we found evidence for increased stabilization of colorectal microvessels, but no such change in melanoma vessels. CONCLUSIONS: Overall, our study suggests that while heterogeneous expression of VEGFR2 is a feature of human tumors, it may not affect response to low dose metronomic cyclophosphamide treatment and possibly other anti-angiogenic approaches. It remains to be seen whether this heterogeneity is partly responsible for the variable clinical success seen to date with targeted anti-VEGFR2 therapy.