Development of prednisone resistance in naïve canine lymphoma: Longitudinal evaluation of NR3C1α, ABCB1, and 11ß-HSD mRNA expression.

Prednisone resistance develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids. We investigated naturally occurring mechanisms of prednisone resistance in seven dogs with naïve multicentric lymphoma, treated with oral prednisone; four dogs were administered concurrent cytotoxic chemotherapy. Expression of NR3C1α, ABCB1 (formerly MDR1), 11ß-HSD1, and 11ß-HSD2 mRNA was evaluated in neoplastic lymph nodes by real-time RT-PCR. Changes of expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Clinical resistance to prednisone was observed after a median of 68 days (range: 7-348 days) after initiation of treatment. Relative to pretreatment samples, prednisone resistance was associated with decreased NR3C1α expression in biopsies of all dogs with high-grade lymphoma (six dogs, p=.031); one dog with indolent T-zone lymphoma had increased expression of NR3C1α. Resistance was not consistently associated with changes in ABCB1, 11ß-HSD1, or 11ß-HSD2 expression. Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for changes in expression of ABCB1, 11ß-HSD1, and 11ß-HSD2 in the emergence of prednisone resistance in lymphoma-bearing dogs.

Cutaneous and subcutaneous metastasis of appendicular osteosarcoma in dogs: 20 cases.

BACKGROUND: Metastasis of appendicular osteosarcoma is most common to the lungs and is generally considered a terminal event in dogs. Behavior and prognosis associated with cutaneous or subcutaneous metastases (CSM) is poorly defined. OBJECTIVE: Describe the population and gather prognostic information regarding appendicular osteosarcoma with CSM in dogs. ANIMALS: Twenty dogs with appendicular osteosarcoma and CSM. METHODS: Retrospective case series. Medical records were searched to identify dogs diagnosed with appendicular osteosarcoma that developed CSM. Demographic data, order of metastatic events, and CSM clinical features were evaluated. Kaplan-Meier survival curves were constructed and log-rank tests were used to compare survival between groups of dogs. RESULTS: In 19 dogs (95%), CSM was an incidental finding. Seventeen dogs (85%) developed pulmonary metastasis, and 1 dog (5%) developed bone metastasis. No other metastatic sites were detected before euthanasia. The median CSM-free interval and CSM survival time were 160 days (range: 0-542 days) and 55 days (range: 5-336 days), respectively. The median CSM survival time was significantly longer for dogs treated with surgery and chemotherapy (94 days) or chemotherapy only (64 days) than for dogs that did not receive these treatments (11 days) (P = .002 and P = .03, respectively). No other factors were associated with survival after diagnosis of CSM. CONCLUSION AND CLINICAL IMPORTANCE: The skin or subcutaneous tissue can be the first osteosarcoma metastatic site detected. After CSM diagnosis, the prognosis is grave with median survival <2 months. Although this finding could have been biased by case selection, treatment with surgery and chemotherapy may improve outcome.

Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells.

Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications.

Canine reference intervals for coagulation markers using the STA Satellite(R) and the STA-R Evolution(R) analyzers.

The aim of the current study was to determine canine reference intervals for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and antithrombin (AT) according to international recommendations. The STA Satellite(R) coefficients of variation of within-laboratory imprecision were 3.9%, 1.3%, 6.9%, and 5.1% for PT, APTT, fibrinogen, and AT, respectively. At 4 degrees C, citrated specimens were stable up to 8 hr for whole blood and 36 hr for plasma, except for APTT, which increased slightly (<1 sec). Nonparametric reference intervals determined in citrated plasma from 139 healthy fasting purebred dogs were 6.9-8.8 sec, 13.1-17.2 sec, 1.24-4.30 g/l, and 104-188% for PT, APTT, fibrinogen, and AT, respectively. Based on Passing-Bablok comparison between STA Satellite and STA-R Evolution(R) using 60 frozen specimens from a canine plasma bank, the corresponding reference intervals were transferred to the STA-R Evolution: 7.1-9.2 sec, 12.9-17.3 sec, 1.20-4.43 g/l, and 94-159% for PT, APTT, fibrinogen, and AT, respectively.