Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma. Based on our recent demonstration that MT1-MMP phosphorylation is involved in the growth of fibrosarcoma tumors, we examined the potential role of phosphorylated MT1-MMP in neuroblastoma progression.</p> <p>Methods</p> <p>Tyrosine phosphorylated MT1-MMP was immunostained on tissue microarray samples from 55 patients with neuroblastoma detected by mass screening (known to be predominantly associated with favourable outcome), and from 234 patients with standard diagnosed neuroblastoma. In addition, the effects of a non phosphorylable version of MT1-MMP on neuroblastoma cell migration and proliferation were investigated within three-dimensional collagen matrices.</p> <p>Results</p> <p>Although there is no correlation between the extent of tyrosine phosphorylation of MT1-MMP (pMT1-MMP) and MYCN amplification or clinical stage, we observed greater phosphorylation of pMT1-MMP in standard neuroblastoma, while it is less evident in neuroblastoma from mass screening samples (P = 0.0006) or in neuroblastoma samples from patients younger than one year (P = 0.0002). <it>In vitro </it>experiments showed that overexpression of a non-phosphorylable version of MT1-MMP reduced MT1-MMP-mediated neuroblastoma cell migration and proliferation within a three-dimensional type I collagen matrix, suggesting a role for the phosphorylated enzyme in the invasive properties of neuroblastoma cells.</p> <p>Conclusion</p> <p>Overall, these results suggest that tyrosine phosphorylated MT1-MMP plays an important role in neuroblastoma progression and that its expression is preferentially observed in tumor specimens from neuroblastoma patients showing poor clinical outcome.</p

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Healthcare workers' industrial action in Nigeria: A cross-sectional study through the lens of Nigerian Physicians

Background The Nigerian health system has been plagued with numerous healthcare worker strikes (industrial action) at all levels. The purpose of this study is to document physicians’ views on healthcare worker-initiated strike action in Nigeria and represent a follow-on to a previous study where poor leadership and management were cited as the most common cause of strike action by healthcare workers. Methods A cross-sectional, descriptive study was executed between April and June 2017. We used a self-administered pre-tested structured questionnaire with open-ended questions to allow for better expression of participants’ views. Participants were drawn mainly from the recently concluded West African College of Physicians (WACP)/Royal College of Physicians (RCP) Millennium Development Goal 6 Partnership for African Clinical Training (M-PACT) course. They represented the six geopolitical zones of Nigeria. Data were analysed using SPSS v 23. Simple frequencies were performed, and relevant tables/charts were developed. Results A total of 58 physicians (out of 131 participants reached) responded to the study, giving a response rate of 44.3%. 62.1% were males, 67.9% were between the ages of 30 and 39 years, and over 60% of respondents graduated prior to 2010. Poor staff welfare was cited by 16.7% as the commonest cause of strikes in the healthcare system. Other causes cited were salary issues (13.9%), leadership and management (13.9%), poor hospital infrastructure (11.1%), poor guidelines and services (11.1% each) and inter-professional disputes (5.6%). The negative consequences of strikes, the groups who benefit from them and solutions to the strikes were enumerated, including training physicians in leadership skills by 98.2% of respondents. Conclusion Poor staff welfare, salary and leadership/management and governmental inability to implement agreements were the common causes of healthcare worker strikes in this study. These strikes resulted in disruption to service delivery and training programmes, increased morbidity and mortality of patients and loss of confidence in the hospitals and the healthcare professions. The participants recommended that the Federal Government respects agreements made with the management of healthcare institutions, implements the National Health Act and ensures that only leaders and managers who are formally trained are appointed to healthcare management positions