Bupivacaine liposomal injectable suspension does not provide improved pain control in dogs undergoing abdominal surgery.

OBJECTIVE: To evaluate the difference in postoperative pain scores of dogs undergoing abdominal surgery receiving surgical incision infiltration of saline or bupivacaine liposomal injectable suspension (BLIS). ANIMALS: 40 dogs undergoing exploratory laparotomy. METHODS: Dogs were prospectively enrolled and randomized to receive either BLIS or saline surgical incision infiltration. All dogs received 5.3 mg of BLIS/kg or an equal volume of saline infiltrated in the muscle/fascia, subcutaneous tissue, and intradermal layer during closure. All dogs received a standardized postoperative pain management protocol. Pain assessment was performed at select time points postoperatively by blinded observers with an electronic algometer, short version of the Glasgow Composite Measure Pain Scale (GCMPS), and indirect measures of pain, including systolic blood pressure, heart rate, and serum cortisol levels. RESULTS: At day 0, blood pressure was higher in the saline group (149.6 vs 125.8 mm Hg; P = .006). At day 3, GCMPS was lower in the BLIS group (BLIS = 1, saline = 2, P = .027), though both average GCMPS scores were low and only 10 dogs were available for day 3 assessments (6 BLIS and 4 saline). No other differences in algometer readings, GCMPS scores, other measured parameters, or need for rescue analgesia were present between BLIS and saline groups at any time point. There was no difference in postoperative incisional infection rate or complications. CLINICAL RELEVANCE: Use of BLIS for exploratory laparotomy did not provide improved pain control over postoperative opioid administration alone. Patients that received BLIS had no increase in short-term complications.

The use of lateral arthroscopy portals for the management of bilateral osteochondritis dissecans of the radial head in an English bulldog.

OBJECTIVE: To report a case of bilateral radial head osteochondritis dissecans (OCD) in a dog treated via lateral elbow arthroscopy portals. STUDY DESIGN: Case report. ANIMALS: Six month old female spayed English bulldog. METHODS: The dog was presented for a left thoracic limb lameness localized to the elbow. Computed tomography revealed bilaterally symmetrical mineralized fragments in the lateral compartment of the elbow joint and blunting of the medial coronoid processes. The fragments were associated with a thin donation bed along the caudolateral articular surface of the radial head with moderate surrounding subchondral bone sclerosis. Bilateral elbow arthroscopy was pursued. Arthroscopy was initiated via a standard medial approach, which allowed for abrasion arthroplasty of the radial incisure and medial coronoid process but provided insufficient access to the radial head lesions. A lateral arthroscopic approach was subsequently performed and provided excellent access to the radial head for fragment retrieval and abrasion arthroplasty. RESULTS: Histopathology of the radial head fragments revealed mild cartilage degeneration and retention of cartilaginous cores within subchondral bone, consistent with OCD. Complete resolution of lameness and elbow pain were observed on clinical examination 5 months postoperatively. CONCLUSION: Radial head OCD can occur as a rare component of elbow dysplasia in growing dogs, and fragment retrieval with abrasion arthroplasty via lateral arthroscopic portals may be an effective treatment option.

E-Cadherin Represses Anchorage-Independent Growth in Sarcomas through Both Signaling and Mechanical Mechanisms.

CDH1 (also known as E-cadherin), an epithelial-specific cell-cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-to-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB1 (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell-cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth. IMPLICATIONS: We highlight how E-cadherin can restrict aggressive behavior in sarcomas through both biochemical signaling and biomechanical effects.

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells.

Phenotypic plasticity refers to a phenomenon in which cells transiently gain traits of another lineage. During carcinoma progression, phenotypic plasticity drives invasion, dissemination and metastasis. Indeed, while most of the studies of phenotypic plasticity have been in the context of epithelial-derived carcinomas, it turns out sarcomas, which are mesenchymal in origin, also exhibit phenotypic plasticity, with a subset of sarcomas undergoing a phenomenon that resembles a mesenchymal-epithelial transition (MET). Here, we developed a method comprising the miR-200 family and grainyhead-like 2 (GRHL2) to mimic this MET-like phenomenon observed in sarcoma patient samples.We sequentially express GRHL2 and the miR-200 family using cell transduction and transfection, respectively, to better understand the molecular underpinnings of these phenotypic transitions in sarcoma cells. Sarcoma cells expressing miR-200s and GRHL2 demonstrated enhanced epithelial characteristics in cell morphology and alteration of epithelial and mesenchymal biomarkers. Future studies using these methods can be used to better understand the phenotypic consequences of MET-like processes on sarcoma cells, such as migration, invasion, metastatic propensity, and therapy resistance.

Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2.

Phenotypic plasticity involves a process in which cells transiently acquire phenotypic traits of another lineage. Two commonly studied types of phenotypic plasticity are epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). In carcinomas, EMT drives invasion and metastatic dissemination, while MET is proposed to play a role in metastatic colonization. Phenotypic plasticity in sarcomas is not well studied; however, there is evidence that a subset of sarcomas undergo an MET-like phenomenon. While the exact mechanisms by which these transitions occur remain largely unknown, it is likely that some of the same master regulators that drive EMT and MET in carcinomas also act in sarcomas. In this study, we combined mathematical models with bench experiments to identify a core regulatory circuit that controls MET in sarcomas. This circuit comprises the microRNA 200 (miR-200) family, ZEB1, and GRHL2. Interestingly, combined expression of miR-200s and GRHL2 further upregulates epithelial genes to induce MET. This effect is phenocopied by downregulation of either ZEB1 or the ZEB1 cofactor, BRG1. In addition, an MET gene expression signature is prognostic for improved overall survival in sarcoma patients. Together, our results suggest that a miR-200, ZEB1, GRHL2 gene regulatory network may drive sarcoma cells to a more epithelial-like state and that this likely has prognostic relevance.