European journal of clinical investigation
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Noncentral nervous system cancer and the brain share an interesting and complex relation, with an emerging body of evidence showing that cancer patients are at an increased risk of developing cognitive problems. In contrast, population-based studies consistently find an inverse link between cancer and dementia, that is patients with dementia having a lower risk of subsequently developing cancer, and cancer patients being less often diagnosed with dementia. Different biological processes such as inversely activated cell proliferation and survival pathways have been suggested to have an important role underlying this inverse association. ⋯ In fact, emerging evidence now suggests that cancer and dementia might share a positive association. This narrative review summarises the current literature on cancer, cognitive problems and dementia. Moreover, different strategies will be discussed to reduce the impact of potential methodological biases on the association between cancer and dementia, trying to reveal the true direction of this link.
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Eur. J. Clin. Invest. · Nov 2018
ReviewMonoclonal antibody-mediated killing of tumour cells by neutrophils.
Neutrophils represent the most abundant population of circulating cytotoxic effector cells. Moreover, their number can be easily increased by treatment with granulocyte-colony stimulating factor or granulocyte macrophage-colony stimulating factor, without the need for ex vivo expansion. ⋯ There is limited evidence that neutrophils play a prominent role in current immunoglobulin G-based immunotherapy. However, as IgA induces neutrophil recruitment, novel therapeutic strategies that aim to target the IgA Fc receptor FcαRI may fully unleash the potential of enlisting neutrophils as cytotoxic effector cells in antibody therapy of cancer.
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Eur. J. Clin. Invest. · Nov 2018
ReviewCXCR4, the master regulator of neutrophil trafficking in homeostasis and disease.
Chemokines play a critical role in orchestrating the distribution and trafficking of neutrophils in homeostasis and disease. ⋯ In this review, we focus on the role of CXCR4/CXCL12 chemokine axis in regulating neutrophil release from the bone marrow and the trafficking of senescent neutrophils back to the bone marrow for clearance under homeostasis and disease. We also discuss the role of CXCR4 in fine-tuning neutrophil responses in the context of inflammation.
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Neutrophils are one of the most important effector cells of the innate immune response (1). They are traditionally seen as a homogenous population of short-lived cells mainly involved in the defence against extracellular microorganisms by phagocytosis and intracellular killing (1,2). The cells contain a large armamentarium that aids in this function and ranges from the production of reactive oxygen species by a membrane-bound NADPH oxidase to cytotoxic proteins and peptides residing in the different granules present in the cytoplasm (3). ⋯ It is not clear whether these cells belong to separate parallel lineages originating from the bone marrow or that neutrophils become instructed in the distant tissues, thus changing their phenotypes. In addition, functional heterogeneity in a phenotypically homogenous population of neutrophils adds to the complexity of neutrophil phenotypes(5). This article will review the current literature describing the heterogeneity within the neutrophil compartment with respect to both phenotype and function in health and disease.
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Eur. J. Clin. Invest. · Nov 2018
ReviewEnergy metabolism of white adipose tissue and insulin resistance in humans.
Insulin resistance not only occurs in obesity, but also in lipodystrophy. Although adipose tissue mass affects metabolic fluxes and participates in interorgan crosstalk, the role of energy metabolism within white adipose tissue for insulin resistance is less clear. ⋯ Abnormal mitochondrial function in human white adipose tissue likely contributes to the secretion of lipid metabolites and lactate, which are linked to insulin resistance in peripheral tissues. However, the relevance of adipose tissue energy metabolism for the regulation of human insulin sensitivity remains to be further elucidated.