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Chambers, D.

Publications and source records attributed to Chambers, D..

2 recordsLinked to original sources

Dynamical Systems Models for Plasma Dilution

Recent experiments provide evidence that diluting the blood plasma restores the plasma environment to a more youthful level at least partially restoring the health of organs and tissues throughout the body. We propose that a dynamical-systems model representing the plasma constituents could support the optimization process and help determine the appropriate dilution level, frequency and any simultaneous plasma infusions to achieve the most favorable outcome. We use a combination of a gradient descent, a simulated annealing and a genetic algorithm to find a population of models that fit illustrative data. We analyze this population and present distributions of the model parameters and include a collection of plots of the dilution process for illustrative models. We then consider modifications of the dilution in order to illustrate what predictions might be possible had we more data to disambiguate the model.

biophysics↗

Transcription Profile And Pathway Analysis Of The Endocannabinoid Receptor Inverse Agonist AM630 In The Core And Infiltrative Boundary Of Human Glioblastoma Cells

BackgroundWe have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumor cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. ResultsThe core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists. ConclusionOur results highlight the different responsiveness of the core and invasive margin cells. Taken together, whilst our findings identify AM630 as an anti-neoplastic drug, showing a high correlation with known anti-proliferative drugs, we find distinct drug sensitivies of the infiltrative margin relative to contrast-enhanced core regions of GBM upon which failed molecular targeted therapies to date have been predicated.

cancer biology↗