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Du Four S.,Vrije Universiteit Brussel | Maenhout S.K.,Vrije Universiteit Brussel | De Pierre K.,UZ Brussel | Renmans D.,Vrije Universiteit Brussel | And 4 more authors.
OncoImmunology | Year: 2015

Melanoma patients are at a high risk of developing brain metastases, which are strongly vascularized and therefore have a significant risk of spontaneous bleeding. VEGF not only plays a role in neo-angiogenesis but also in the antitumor immune response. VEGFR-targeted therapy might not only have an impact on the tumor vascularization but also on tumor-infiltrating immune cells. In this study, we investigated the effect of axitinib, a small molecule TKI of VEGFR-1, -2, and -3, on tumor growth and on the composition of tumor-infiltrating immune cells in subcutaneous and intracranial mouse melanoma models. In vivotreatment with axitinib induced a strong inhibition of tumor growth and significantly improved survival in both tumor models. Characterization of the immune cells within the spleen and tumor of tumor-bearing mice respectively showed a significant increase in the number of CD3+CD8+ T cells and CD11b+ cells of axitinib-treated mice. More specifically, we observed a significant increase of intratumoral monocytic myeloid-derived suppressor cells (moMDSCs; CD11b+Ly6ChighLy6G-). Interestingly, in vitro proliferation assays showed that moMDSCs isolated from spleen or tumor of axitinib-treated mice had a reduced suppressive capacity on a per cell basis as compared to those isolated from vehicle-treated mice. Moreover, MDSCs from axitinib-treated animals displayed the capacity to stimulate allogeneic T cells. Thus, treatment with axitinib induces differentiation of moMDSC toward an antigen-presenting phenotype. Based on these observations, we conclude that the impact of axitinib on tumor growth and survival is most likely not restricted to direct anti-angiogenic effects but also involves important effects on tumor immunity. © 2015 Taylor & Francis Group, LLC. Source


Sannino G.,CNR Institute of Neuroscience | Melillo P.,The Second University of Naples | Stranges S.,Luxembourg Institute of Health LIH | Pietro G.D.,CNR Institute of Neuroscience | Pecchia L.,University of Warwick
Journal of Medical Systems | Year: 2015

Orthostatic Hypotension is defined as a reduction of systolic and diastolic blood pressure within 3 minutes of standing, and may cause dizziness and loss of balance. Orthostatic Hypotension has been considered an important risk factor for falls since 1960. This paper presents a model to predict the systolic blood pressure drop due to orthostatic hypotension, relying on heart rate variability measurements extracted from 5 minute ECGs recorded before standing. This model was developed and validated with the leave-one-out cross-validation technique involving 10 healthy subjects, and finally tested with an additional 5 healthy subjects, whose data were not used during the training and cross-validation process. The results show that the model predicts correctly the systolic blood pressure drop in 80 % of all experiments, with an error rate below the measurement error of a sphygmomanometer digital device. © 2015, Springer Science+Business Media New York. Source


Kandala N.-B.,Luxembourg Institute of Health LIH | Kandala N.-B.,Northumbria University | Emina J.B.O.,University of Kinshasa
Journal of Biosocial Science | Year: 2016

Summary In sub-Saharan Africa, nutrition research has primarily focused on under-nutrition, particularly among vulnerable children. However, there is increasing evidence of an emerging nutrition transition with extremely high rates of obesity, and malnutrition in women may be a problem that is insufficiently recognized and inadequately documented. This analysis was based on the 2008 Nigerian Demographic and Health Survey (NDHS), which included 27,967 women aged 15-49 years. Individual-level data were collected for socio-demographic characteristics and aggregated to the country's 37 states. A Bayesian geo-Additive mixed model was used to map the geographic distribution of under-nutrition at the state level, accounting for individual-level risk factors. The results reveal that 12.0% of the population were underweight, while 20.9% were either overweight or obese, based on BMI. The northern states of Sokoto and Yobe/Borno and the southern state of Delta had the highest prevalence of underweight, while states in the centre had the lowest underweight prevalence. Underweight women were more likely to be from poorer households compared with their counterparts from the richest wealth index, which were consistently associated with lower odds of being underweight (posterior odds ratio (POR) and 95% credible region (CR): 0.56 [0.46, 0.70]). On the other hand Muslim women (1.61 [1.10, 2.23]), those of traditional religion (2.12 [1.44, 3.00]), those from the Fulani ethnic group (2.90 [1.64, 5.55]) and those living in Yobe state were all consistently associated with higher odds of being underweight. This study demonstrates that underweight is a major public health problem in Nigeria affecting adult females in the northern states of Nigeria. Identifying risk factors and the need to account for sex, spatial and socio-cultural issues are crucial to develop and implement evidence-informed strategies and interventions for lifestyle health promotion. Copyright © Cambridge University Press, 2015. Source


Gallien S.,Luxembourg Institute of Health LIH | Domon B.,Luxembourg Institute of Health LIH
Methods | Year: 2015

Quantitative proteomics has benefited from the recent development of mass spectrometers capable of high-resolution and accurate-mass (HR/AM) measurements. While targeted experiments are routinely performed on triple quadrupole instruments in selected reaction monitoring (SRM; often referred as multiple reaction monitoring, MRM) mode, the quadrupole-orbitrap mass spectrometers allow quantification in MS/MS mode, also known as parallel reaction monitoring (PRM). This technique is characterized by higher selectivity and better confidence in the assignment of the precursor and fragment ions, and thus translates into an improved analytical performance. More fundamentally, PRM introduces a change of the overall paradigm of targeted experiments, by the decoupling of the acquisition and data processing. They rely on two distinct steps, with a simplified acquisition method in conjunction with a flexible, iterative, post-acquisition data processing.This account describes in detail the different steps of a PRM experiment, which include the design of the acquisition method, the confirmation of the identity of the analytes founded upon a full MS/MS fragmentation pattern, and the quantification based on the extraction of specific fragment ions (selected post-acquisition) using tight mass tolerance. The different types of PRM experiments, defined as large-scale screening or precise targeted quantification using calibrated internal standards, together with the considerations on the selection of experimental parameters are discussed. © 2015 Elsevier Inc. Source


Azuaje F.,Luxembourg Institute of Health LIH | Tiemann K.,Luxembourg Institute of Health LIH | Niclou S.P.,Luxembourg Institute of Health LIH
Cell Communication and Signaling | Year: 2015

The alteration of the epidermal growth factor receptor (EGFR)-driven signaling network is a characteristic feature of glioblastomas (GBM), and its inhibition represents a treatment strategy. However, EGFR-targeted interventions have been largely ineffective. Complex perturbations in this system are likely to be central to tumor cells with high adaptive capacity and resistance to therapies. We review key concepts and mechanisms relevant to EGFR-targeted treatment resistance at a systems level. Our understanding of treatment resistance as a systems-level phenomenon is necessary to develop effective therapeutic options for GBM patients. This is allowing us to go beyond the notion of therapeutic targets as single molecular components, into strategies that can weaken cancer signaling robustness and boost inherent network-level vulnerabilities. © 2015 Azuaje et al.; licensee BioMed Central. Source

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