77 research outputs found

    Low Doses of Ionizing Radiation Promote Tumor Growth and Metastasis by Enhancing Angiogenesis

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    Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols

    The Epidemiology of Blood-Contaminated Needlestick Injuries Among Veterinarians in Portugal

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    Needlestick injuries (NIs) are considered a substantial occupational health and safety hazard in contemporary health care practice. Unlike human medicine where much effort has been devoted to reduce the incidence of these events, the same aggressive approach has not been used in veterinary medicine. This study investigated the occurrence of blood-contaminated NIs in Portuguese veterinarians. Participants of a veterinary meeting were asked to complete a questionnaire-based survey. Differences in NI exposure rates by sex, years in practice, and animal interaction during childhood were evaluated using the chi-square test. Univariate and multivariate logistic regression analyses were performed to produce predicted probabilities for NI episodes in veterinarians. From the total of 373 enrolled veterinarians, 293 (78.5%) reported having had at least one NI during their professional life. Veterinarians working with dogs were more likely to have experienced a NI (adjusted odds ratio [aOR]: 145.74, P < .001). The high level of NIs observed in these professionals shows that NIs are a potential occupational health problem in Portuguese veterinarians, with the possibility for transmission of haematogenous zoonosis.This work was supported by the award number Ovislab ICT-2013-05-004-5314 ID-64757 from QREN/FEDER and the award number SFRH/BPD/64686/2009SFRH/BPD/64686/2009 from Fundação para a Ciência e Tecnologia (FCT)

    The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population

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    Purpose To examine disease profile of tubercular uveitis (TBU) in Paediatric population. Methods Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed. Results Mean age of disease presentation was 12.8 (range 4-18 years), with predominance of males (n = 14/20; 70.0%) and Asian ethnicity (n = 25/29; 86.2%). Posterior uveitis (n = 14/28; 50%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7% (n = 11/17). Incidence of optic disc edema and macular edema was higher in children (n = 8/18; 44.4% and n = 5/18; 27.8%, respectively) than in adults (n = 160/942; 16.9% and n = 135/942; 14.3%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (P =.006). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8% (n = 1/21). Conclusions Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome

    Tubercular uveitis : nuggets from Collaborative Ocular Tuberculosis Study (COTS)-1

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    Background: Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Purpose: Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Methods: Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Results: Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. Conclusion: The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data
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