Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance.

Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting that lineage plasticity facilitates therapeutic resistance. The mechanisms underlying prostate cancer lineage plasticity are incompletely understood. Studying mouse models, we demonstrate that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2. Clinically relevant Ezh2 inhibitors restore androgen receptor expression and sensitivity to antiandrogen therapy. These findings uncover genetic mutations that enable prostate cancer progression; identify mouse models for studying prostate cancer lineage plasticity; and suggest an epigenetic approach for extending clinical responses to antiandrogen therapy.

Imaging diagnosis--disseminated peritoneal leiomyomatosis in a dog.

A 17-month-old male Labrador retriever presented for evaluation of an abdominal mass felt during abdominal palpation. Multiple variably sized cystic masses were identified on sonographic and radiographic images. Exploratory laparotomy revealed multiple peritoneal masses that exhibited atypical contractions and lacked an identifiable organ of origin. Histology and immunohistochemistry of multiple surgically excised masses was consistent with benign tumors of smooth muscle origin (leiomyomas). The presence of multiple peritoneal leiomyomas in this dog is consistent with disseminated peritoneal leiomyomatosis. Two years after diagnosis and multiple surgical interventions, continual insidious enlargement of leiomyomas was identified on ultrasound and CT.

Outcome of 45 dogs with laryngeal paralysis treated by unilateral arytenoid lateralization or bilateral ventriculocordectomy.

The purpose of this retrospective study was to assess risk factors and complications affecting postoperative outcome of dogs with laryngeal paralysis treated by either unilateral arytenoid lateralization (UAL) or bilateral ventriculocordectomy (VCC). Medical records of all dogs having either UAL or VCC between 2000 and 2011 were analyzed. Twenty-five dogs had VCC and 20 dogs had UAL. The overall postoperative complications rates for VCC and UAL were similar (52% and 60%, respectively; P = .0887). Dogs that had UAL were more likely to have acute postoperative respiratory distress and aspiration pneumonia (P = .0526). Dogs with VCC were more likely to have chronic postoperative respiratory distress and aspiration pneumonia (P = .0079). Revision surgery was required in 6 dogs (24%) following VCC and 2 dogs (10%) following UAL. Sex, breed, presenting complaint, type of service provided, and concurrent diseases were not significantly associated with higher risk of either death or decreased survival time postoperatively with either procedure. Overall postoperative complication rates, required revision surgeries, and episodes of aspiration pneumonia were similar in dogs undergoing UAL and VCC surgeries. Dogs that had VCC appeared to have an increased risk of lifelong complications postoperatively compared with UAL; therefore, VCC may not be the optimal choice for treatment of laryngeal paralysis.

Thoracic limb alignment in healthy labrador retrievers: evaluation of standing versus recumbent frontal plane radiography.

OBJECTIVE: To report thoracic limb alignment values in healthy dogs; to determine if limb alignment values are significantly different when obtained from standing versus recumbent radiographic projections. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Labrador Retrievers (n = 45) >15 months of age. METHODS: Standing and recumbent radiographs were obtained and limb montages were randomized before analysis by a single investigator blinded to dog, limb, and limb position. Twelve limb alignment values were determined using the CORA methodology. Measurements were performed in triplicate and intra-observer variability was evaluated by intra-class correlation coefficient (ICC). Limb alignment values were reported as mean ± SD and 95% confidence intervals. Linear mixed models were used to determine if significant associations existed between limb alignment values and limb, limb position, gender, age, weight, and body condition score. RESULTS: There were significant differences in standing and recumbent limb alignment values for all values except elbow mechanical axis deviation (eMAD). Limb, gender, age, body weight, and body condition score had no effect. ICC values ranged from 0.522 to 0.758, indicating moderate to substantial agreement for repeated measurements by a single investigator. CONCLUSIONS: Limb alignment values are significantly different when determined from standing versus recumbent radiographs in healthy Labrador Retrievers.

Two cases of paraprostatic cysts in castrated male dogs.

Two castrated male dogs presented for evaluation of tenesmus. Presurgical evaluations included complete physical examinations, serum biochemistry, abdominal ultrasonography, and MRI (case 2 only). Paraprostatic cysts were diagnosed in both cases based on the results of abdominal ultrasonography, MRI, and histopathology of tissue samples obtained during exploratory laparotomy. To the authors' knowledge, the two cases presented herein are the first documented cases of paraprostatic cysts that developed after castration in male dogs. Paraprostatic cysts should be considered in the differential diagnoses for castrated male dogs with prostatic disease.