by Keyword: Animal models

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Noguera-Ortega, Estela, Secanella-Fandos, Silvia, Eraña, Hasier, Gasión, Jofre, Rabanal, Rosa M., Luquin, Marina, Torrents, Eduard, Julián, Esther, (2016). Nonpathogenic Mycobacterium brumae inhibits bladder cancer growth in vitro, ex vivo, and in vivo European Urology Focus 2, (1), 67-76

Background Bacillus Calmette-Guérin (BCG) prevents tumour recurrence and progression in non–muscle-invasive bladder cancer (BC). However, common adverse events occur, including BCG infections. Objective To find a mycobacterium with similar or superior antitumour activity to BCG but with greater safety. Design In vitro, ex vivo, and in vivo comparisons of the antitumour efficacy of nonpathogenic mycobacteria and BCG. Intervention The in vitro antitumour activity of a broad set of mycobacteria was studied in seven different BC cell lines. The most efficacious was selected and its ex vivo capacity to activate immune cells and its in vivo antitumour activity in an orthotopic murine model of BC were investigated. Outcome measurements and statistical analysis Growth inhibition of BC cells was the primary outcome measurement. Parametric and nonparametric tests were use to analyse the in vitro results, and a Kaplan-Meier test was applied to measure survival in mycobacteria-treated tumour-bearing mice. Results and limitations Mycobacterium brumae is superior to BCG in inhibiting low-grade BC cell growth, and has similar effects to BCG against high-grade cells. M. brumae triggers an indirect antitumour response by activating macrophages and the cytotoxic activity of peripheral blood cells against BC cells. Although no significant differences were observed between BCG and M. brumae treatments in mice, M. brumae treatment prolonged survival in comparison to BCG treatment in tumour-bearing mice. In contrast to BCG, M. brumae does not persist intracellularly or in tumour-bearing mice, so the risk of infection is lower. Conclusions Our preclinical data suggest that M. brumae represents a safe and efficacious candidate as a therapeutic agent for non–muscle-invasive BC. Patient summary We investigated the antitumour activity of nonpathogenic mycobacteria in in vitro and in vivo models of non–muscle-invasive bladder cancer. We found that Mycobacterium brumae effectively inhibits bladder cancer growth and helps the host immune system to eradicate cancer cells, and is a promising agent for antitumour immunotherapy.

Keywords: Animal models, Bacillus Calmette-Guérin, Cytokines, Immunomodulation, Immunotherapy, Mycobacteria, Urothelial cell line

Almendros, I., Farré, R., Torres, M., Bonsignore, M. R., Dalmases, M., Ramírez, J., Navajas, D., Montserrat, J. M., (2011). Early and mid-term effects of obstructive apneas in myocardial injury and inflammation Sleep Medicine 12, (10), 1037-1040

Background: Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different comorbidities in OSA patients make it difficult to know their specific effects on the development of cardiovascular injury. The aim of the present study was to investigate whether recurrent obstructive apneas could lead to myocardial injury. Methods: Thirty-six male Sprague-Dawley rats (300-350. g) were either acutely (3. h) or sustainably (5. h/day, for 10. days) subjected to obstructive apneas with a pattern of 15. s each, 60. apneas/h. Corresponding control groups were formed for the acute and sustained models. To assess the induction of systemic inflammation, IL1-β was measured in plasma. Ventricular tissue injury was evaluated by histological techniques (presence of inflammatory cell infiltration, eosin autofluorescence, and detection of apoptosis). Results: After 3. h of obstructive apneas, a significant increase in IL1-β (64.9. ±. 29.6. ng/μl) were observed with respect to the controls (7.3. ±. 1.0. ng/μl), but no myocardial injury was present. Conversely to the acute model, the systemic inflammation triggered by obstructive apneas for 10. days was reduced. However, the percentage of area with enhanced eosin autofluorescence and of apoptotic cells (1.83. ±. 0.35% and 24.4. ±. 1.5%, respectively) was increased when compared to the control group (0.72. ±. 0.20% and 5.0. ±. 2.8%, respectively). Conclusions: This study suggests that obstructive apneas are a potential source of early systemic and ventricular inflammation and myocardial cell injury after sustained apneas application, which could represent an initial phase in the progression of heart disease associated with OSA.

Keywords: Animal models, Inflammation, Myocardial injury, Obstructive sleep apnea

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