Evaluation of the influence of the C-X-C motif chemokine ligand 12 / C-X-C chemokine receptor 4 axis on canine mammary gland tumor cell migration.

C-X-C motif chemokine ligand 12 (CXCL12) is one of the chemokines that binds to C-X-C chemokine receptor 4 (CXCR4) on tumor cell membranes and induces chemotaxis and/or migration. Mammary gland tumors (MGT) are the most common neoplasms in intact female dogs, with local invasion and distant metastasis regarded as problems. However, the influence of the CXCL12/CXCR4 axis on canine MGT cell migration has not been elucidated. This study aimed to evaluate the expression of CXCL12 and CXCR4 in canine MGT cells and tissues and investigate the influence of CXCL12 protein on the migratory ability of MGT cells. CXCL12 expression was evaluated in 10 canine malignant MGT tissues. CXCL12 expression in tumor cells was identified in all examined tissues; however, the staining pattern and intensity differed between the tumors. Immunocytochemistry revealed three canine MGT cell lines as CXCR4-positive. Migratory ability was evaluated using a wound healing assay, and the migration of CXCR4-positive MGT cells was significantly activated by the addition of CXCL12 protein. This influence was canceled by pre-treatment with a CXCR4 antagonist. The results of our study suggest that the CXCL12/CXCR4 axis may be associated with the migration of canine MGT.

Assessment of Nasal Structure Using CT Imaging of Brachycephalic Dog Breeds.

The response to treatment of brachycephalic airway syndrome (BAS) varies among brachycephalic dog breeds. We hypothesized that variations in nasal structure are one of the factors responsible for this difference. To confirm this variation, we measured the ratio of the airway cross-sectional area to the total nasal cavity area (AA/NC) in three brachycephalic dog breeds. Head CT images of French bulldogs, shih tzus, and pugs were retrospectively collected. Four specific transverse planes were used to calculate AA/NC ratios. Fifty brachycephalic dogs were included in the study: French bulldogs (n = 20), shih tzus (n = 20), and pugs (n = 10). The AA/NC ratio of Shih Tzus was larger in the rostral nasal cavity and smaller toward the caudal area, whereas the other two breeds showed an inverse tendency. The results obtained from the current research indicate that the AA/NC ratio can be used to evaluate the structure of the nasal cavity. Moreover, analyzing the point with the smallest AA/NC ratio can be useful in quantifying nasal airway obstruction and the severity of BAS. These results will be useful in understanding the complexity of BAS pathophysiology and in the implementation of treatment.

Thoracic Wall Reconstruction with Dorsal Diaphragmatic Traction and Preservation of Diaphragmatic Attachments in a Dog with Resection of the 11-13th Ribs.

A 9-year-old, 4.7 kg, spayed female Chihuahua presented with a 3.5 cm soft tissue sarcoma on the dorsal right thoracic wall. The tumor was resected, including the 11−13th ribs, resulting in a caudal dorsal thoracic wall defect. The defect was reconstructed with direct traction of part of the diaphragm dorsally, preserving the diaphragmatic attachments to the body wall, and the diaphragm was sutured to the surrounding ribs and muscles. Possible respiratory complications, including paradoxical respiration and exercise intolerance, were not observed during the perioperative or postoperative observation periods. This novel procedure is expected to be an option for caudal thoracic wall reconstruction when the diaphragmatic attachments remain intact even after the resection of the last rib. In addition, this procedure can be performed in dogs weighing <5 kg, with small pleural cavities and without respiratory disorders.

Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.

SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2. The body weight of transgenic mice increased by 5.0% (P < 0.05) compared with control wild-type littermates on a normal chow diet, but not on a high-fat diet. Glucose tolerance and insulin sensitivity were mildly but significantly impaired in the transgenic mice only when maintained on the normal chow diet, as shown by 1.2-fold increase in glucose area under the curve over control levels at 9 months old. Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver. In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased. Consistently, hepatic glycogen content was reduced in the 9-month-old transgenic mice. Structure and insulin content were histologically normal in the pancreatic islets of transgenic mice. These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.