ABSTRACT
Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.
Subject(s)
Interleukin-17/immunology , Arthritis, Psoriatic , Arthritis, Rheumatoid , Humans , Interleukin-17/antagonists & inhibitors , Psoriasis , Spondylitis, AnkylosingABSTRACT
Neuroblasts represent the predominant migrating cell type in the adult mouse brain. There are, however, increasing evidences of migration of other neural precursors. This work aims at identifying in vivo endogenous early neural precursors, different from neuroblasts, able to migrate in response to brain injuries. The monoclonal antibody Nilo1, which unequivocally identifies type B astrocytes and embryonic radial glia, was coupled to magnetic glyconanoparticles (mGNPs). Here we show that Nilo1-mGNPs in combination with magnetic resonance imaging in living mice allowed the in vivo identification of endogenous type B astrocytes at their niche, as well as their migration to the lesion site in response to glioblastoma, demyelination, cryolesion or mechanical injuries. In addition, Nilo1(+) adult radial glia-like structures were identified at the lesion site a few hours after damage. For all damage models used, type B astrocyte migration was fast and orderly. Identification of Nilo1(+) cells surrounding an induced glioblastoma was also possible after intraperitoneal injection of the antibody. This opens up the possibility of an early identification of the initial damage site(s) after brain insults, by the migration of type B astrocytes.
Subject(s)
Astrocytes/cytology , Brain/metabolism , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Astrocytes/transplantation , Brain/pathology , Brain Injuries/metabolism , Brain Injuries/pathology , Cell Line, Tumor , Cell Movement , Humans , Immunohistochemistry , Lateral Ventricles/cytology , Lateral Ventricles/metabolism , Magnetic Resonance Imaging , Magnetite Nanoparticles/chemistry , Male , Mice , Mice, Inbred C57BL , Microscopy, Confocal , Neoplastic Stem Cells/cytologyABSTRACT
Bone metastases are a common and distressing effect of cancer, being a major cause of morbidity in many patients with advanced stage cancer, in particular in breast and prostate cancer. Patients with bone metastases can experience complications known as skeletal-related events (SREs) which may cause significant debilitation and have a negative impact on quality of life and functional independence. The current recommended systemic treatment for the prevention of SREs is based on the use of bisphosphonates: ibandronate, pamidronate and zoledronic acid- the most potent one- are approved in advanced breast cancer with bone metastases, whereas only zoledronic acid is indicated in advanced prostate cancer with bone metastases. The 2011 ASCO guidelines on breast cancer, recommend initiating bisphosphonate treatment only for patients with evidence of bone destruction due to bone metastases. Denosumab, a fully human antibody that specifically targets the RANK-L, has been demonstrated in two phase III studies to be superior to zoledronic acid in preventing or delaying SREs in breast and prostate cancer and non-inferior in other solid tumours and mieloma; it's convenient subcutaneous administration and the fact that does not require dose adjustment in cases of renal impairment, make this agent an attractive new therapeutic option in patients with bone metastases. Finally, in a phase III study against placebo, denosumab significantly increased the median metastasis-free survival in high risk non-metastatic prostate cancer, arising the potential role of these bone-modifying agents in preventing or delaying the development of bone metastases.
