Browsing by Author "Yong, V Wee"

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    Reduction of microglial activity in a model of multiple sclerosis by dipyridamole
    (BioMed Central, 2013-07-18) Sloka, Scott; Metz, Luanne M; Hader, Walter; Starreveld, Yves; Yong, V Wee
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    Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells
    (Nature Publishing Group, 2013-12-08) Sarkar, Susobhan; Doring, Axinia; Zemp, Franz J; Silva, Claudia; Lun, Xueqing; Wang, Xiuling; Kelly, John; Hader, Walter; Hamilton, Mark; Mercier, Philippe; Dunn, Jeffery F.; Kinniburgh, Dave; van Rooijen, Nico; Robbins, Stephen; Forsyth, Peter; Cairncross, Gregory; Weiss, Samuel; Yong, V Wee
    Brain tumor initiating cells (BTICs) contribute to the genesis and recurrence of gliomas. We examined whether the microglia and macrophages that are abundant in gliomas alter BTIC growth. We found that microglia derived from non-glioma human subjects markedly mitigated the sphere-forming capacity of glioma patient–derived BTICs in culture by inducing the expression of genes that control cell cycle arrest and differentiation. This sphere-reducing effect was mimicked by macrophages, but not by neurons or astrocytes. Using a drug screen, we validated amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB enhanced the microglial reduction of BTIC spheres. In mice harboring intracranial mouse or patient-derived BTICs, daily systemic treatment with non-toxic doses of AmpB substantially prolonged life. Notably, microglia and monocytes cultured from glioma patients were inefficient at reducing the sphere-forming capacity of autologous BTICs, but this was rectified by AmpB. These results provide new insights into the treatment of gliomas.
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    Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis
    (2013-11-21) Nathoo, Nabeela; Yong, V Wee; Dunn, Jeffrey F.; Beketskaia, Maria
    Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.