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Summary: Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma.

This paper investigates crystal growth modifiers based on 1,3,5-substituted benzene derivatives. The results show that as expected, the phosphonated derivative inhibits calcite precipitation to a much greater degree than the analogous sulfonate. However, on barium sulfate, both molecules show some crystallization promotion behaviour, with the phosphonate being the more potent promoter overall. Thus, the functional group alone does not determine the impact the organic molecule will have on crystallization. This opens the way for additives that have dual purposes (inhibiting the crystallization of one phase while not impacting or promoting the crystallization of other phases). [ABSTRACT FROM AUTHOR]

Abstract  The synthesis and single-crystal x-ray structure determination of two new trinuclear metal complexes is detailed. In these we utilise the appended iminodiacetate substituents, in [Co(CH3)NH(CH2CO2H)2sar]3, to act as a focus for coordination of other metal ions. Thus, we have made complexes of Cu and Ni utilising the basic carbonates of these metals and [Co(CH3){N(CH2CO2H)2}sar]3 (CoL2) which gave rise to ((CoL2–2H)2M), M = Cu and Ni. The electrochemical study of the latter was inconclusive and provides the impetus for further study. [ABSTRACT FROM AUTHOR]