32 research outputs found

    Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma

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    <p>Abstract</p> <p>Background</p> <p>The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.</p> <p>Methods</p> <p>We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.</p> <p>Results</p> <p>Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).</p> <p>Conclusions</p> <p>The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.</p

    Penicillium

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    Evaluation of the Efficacy and Safety of High Dose Short Duration Enrofloxacin Treatment Regimen for Uncomplicated Urinary Tract Infections in Dogs

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    BACKGROUND: Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10–14 days. Shorter duration antimicrobial regimens have been evaluated in human patients. HYPOTHESIS: A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid. ANIMALS: Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥10(3) CFU/mL of bacteria after cystocentesis. METHODS: Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18–20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75–25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded. RESULTS: There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority. CONCLUSIONS AND CLINICAL IMPORTANCE: HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance

    Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative efficacy trial.

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    Background: Open-label, parallel-group, international trial comparing aztreonam for inhalation solution (AZLI) and tobramycin nebulizer solution (TNS) for cystic fibrosis patients with airway Pseudomonas aeruginosa. Methods: 273 patients (≥ 6 years); randomized to three 28-day courses (AZLI 75 mg [three-times/day] or TNS 300 mg [twice/day]); 28 off-days separated each course. Results: 268 patients were treated (AZLI/TNS: 136/132). Mean baseline FEV1 was 52% predicted. Mean relative changes after 1 course (AZLI: 8.35%; TNS: 0.55%; p&lt;0.001) and mean actual changes across 3 courses (AZLI: 2.05%; TNS: -0.66%; p=0.002) indicated AZLI statistical superiority vs. TNS. AZLI-treated patients had fewer respiratory hospitalizations (p=0.044) and respiratory events requiring additional antipseudomonal antibiotics (p=0.004); both treatments were well tolerated. 133 patients received 1 to 3 courses of AZLI treatment in the open-label extension-period (28-day courses separated by 28 days off-treatment); lung function improvements were comparable regardless of whether patients had received TNS or AZLI in the preceding comparative period. Conclusions: AZLI demonstrated statistical superiority in lung function and a reduction in acute pulmonary exacerbations compared to TNS over 3 treatment courses (ClinicalTrials.gov: NCT00757237)
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