122,908 research outputs found

    Consequences of cell-to-cell P-glycoprotein transfer on acquired multidrug resistance in breast cancer: a cell population dynamics model

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    Cancer is a proliferation disease affecting a genetically unstable cell population, in which molecular alterations can be somatically inherited by genetic, epigenetic or extragenetic transmission processes, leading to a cooperation of neoplastic cells within tumoral tissue. The efflux protein P-glycoprotein (P gp) is overexpressed in many cancer cells and has known capacity to confer multidrug resistance to cytotoxic therapies. Recently, cell-to-cell P-gp transfers have been shown. Herein, we combine experimental evidence and a mathematical model to examine the consequences of an intercellular P-gp trafficking in the extragenetic transfer of multidrug resistance from resistant to sensitive cell subpopulations. We report cell-to-cell transfers of functional P-gp in co-cultures of a P-gp overexpressing human breast cancer MCF-7 cell variant, selected for its resistance towards doxorubicin, with the parental sensitive cell line. We found that P-gp as well as efflux activity distribution are progressively reorganized over time in co-cultures analyzed by flow cytometry. A mathematical model based on a Boltzmann type integro-partial differential equation structured by a continuum variable corresponding to P-gp activity describes the cell populations in co-culture. The mathematical model elucidates the population elements in the experimental data, specifically, the initial proportions, the proliferative growth rates, and the transfer rates of P-gp in the sensitive and resistant subpopulations. We confirmed cell-to-cell transfer of functional P-gp. The transfer process depends on the gradient of P-gp expression in the donor-recipient cell interactions, as they evolve over time. Extragenetically acquired drug resistance is an additional aptitude of neoplastic cells which has implications in the diagnostic value of P-gp expression and in the design of chemotherapy regimensComment: 13 pages, 8 figures, 1 tabl

    QED-Cavity model of microtubules implies dissipationless energy transfer and biological quantum teleportation

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    We refine a QED-cavity model of microtubules (MTs), proposed earlier by two of the authors (N.E.M. and D.V.N.), and suggest mechanisms for the formation of biomolecular mesoscopic coherent and/or entangled quantum states, which may avoid decoherence for times comparable to biological characteristic times. This refined model predicts dissipationless energy transfer along such "shielded" macromolecules at near room temperatures as well as quantum teleportation of states across MTs and perhaps neurons.Comment: 20 pages LATEX, three ps figures incorporate

    Darwinism and Organizational Ecology: A Reply to Reydon and Scholz

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    In an earlier article published in this journal I challenge Reydon and Scholz's (2009) claim that Organizational Ecology is a non-Darwinian program. In this replay to Reydon and Scholz's subsequent response, I clarify the difference between our two approaches denoted by an emphasis her on the careful application of core Darwinian principles and an insistence by Reydon and Scholz on direct biological analogies. On a substantive issue, they identify as being the principle problem for Organizational Ecology, namely, the inability to identify replicators and interactors "of the right sort" in the business domain; this is also shown to be easily addressed with reference to empirical studies of business populations.Peer reviewedFinal Accepted Versio

    Cultural replication and microbial evolution

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    The aim of this paper is to argue that cultural evolution is in many ways much more similar to microbial than to macrobial biological evolution. As a result, we are better off using microbial evolution as the model of cultural evolution. And this shift from macrobial to microbial entails adjusting the theoretical models we can use for explaining cultural evolution
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