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Attenuated reovirus displays oncolysis with reduced host toxicity
Kim, M,Garant, K A,zur Nieden, N I,Alain, T,Loken, S D,Urbanski, S J,Forsyth, P A,Rancourt, D E,Lee, P W K,Johnston, R N Nature Publishing Group 2011 The British journal of cancer Vol.104 No.2
<P><B>Background:</B></P><P>Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures.</P><P><B>Methods:</B></P><P>We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and <I>in vitro</I> transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts.</P><P><B>Results:</B></P><P>Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and <I>in vitro</I> translation confirmed the presence of a truncated <I>σ</I>1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size.</P><P><B>Conclusion:</B></P><P>Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy.</P>
Kim, M.,Jeong, G.,Eom, K.,Cho, E.,Ryu, J.,Kim, H.J.,Kwon, H. Pergamon Press ; Elsevier Science Ltd 2013 INTERNATIONAL JOURNAL OF HYDROGEN ENERGY - Vol.38 No.28
To improve cell performance, the effects of heat treatment time on the electrochemical properties and electrode structure of PTFE-bonded membrane electrode assemblies for PBI-based high-temperature proton exchange membrane fuel cells are investigated. The cell performance is observed to decrease in the high-current-density region rather than in the low-current-density region with increasing heat treatment time at 350 <SUP>o</SUP>C from 1 to 30 min. Microscopic studies reveal remarkable differences in the electrode structure by the agglomeration of dispersed PTFE and adjacent catalyst particles, depending on the heat treatment time. As the heat treatment time increases, only the large pore (secondary pore) volume in the electrode decreases, resulting in increase in mass transport resistance and concentration overpotential in the high-current-density region. Cell performance is not measured without heat treatment because the electrodes are not formed. When the electrodes are heat treated for 1 min at 350 <SUP>o</SUP>C, the best cell performance is obtained, 0.67 V at 200 mA cm<SUP>-2</SUP>.