Adv Exp Med Biol
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The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterised by progressive lack of motor coordination leading to major disability. SCAs show high clinical, genetic, molecular and epidemiological variability. ⋯ The scope of this chapter is to provide an updated information on Machado-Joseph disease (MJD), the most frequent SCA subtype worldwide and other rare spinocerebellar ataxias including dentatorubral-pallidoluysian atrophy (DRPLA), the X-linked fragile X tremor and ataxia syndrome (FXTAS) and the nonprogressive episodic forms of inherited ataxias (EAs). Furthermore, the different therapeutic strategies that are currently being investigated to treat the ataxia and non-ataxia symptoms in SCAs are also described.
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Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. Among the new treatments currently being investigated, immunotherapy is theoretically very attractive since it offers the potential for high tumor-specific cytotoxicity. Increasing numbers of reports demonstrate that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. ⋯ Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response in patients with glioma, where it seems to be safe and without major side effects. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy. Its efficacy should be further determined in randomized, controlled clinical trials.
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The retrotrapezoid nucleus (RTN) is located in the rostral medulla oblongata close to the ventral surface and consists of a bilateral cluster of glutamatergic neurons that are non-aminergic and express homeodomain transcription factor Phox2b throughout life. These neurons respond vigorously to increases in local pCO(2) via cell-autonomous and paracrine (glial) mechanisms and receive additional chemosensory information from the carotid bodies. RTN neurons exclusively innervate the regions of the brainstem that contain the respiratory pattern generator (RPG). ⋯ Phox2b mutations that cause congenital central hypoventilation syndrome in humans prevent the development of RTN neurons in mice. Selective deletion of the RTN Phox2b-VGLUT2 neurons by genetic means in mice eliminates the respiratory chemoreflex in neonates. In short, RTN Phox2b-VGLUT2 neurons are a major nodal point of the CNS network that regulates pCO(2) via breathing and these cells are probable central chemoreceptors.
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Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. ⋯ More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.