Cell uptake
Dotaz
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466 s. : il.
- MeSH
- draslík MeSH
- mozková kůra MeSH
- myši MeSH
- neuroglie MeSH
- neurony MeSH
- spotřeba kyslíku MeSH
- techniky in vitro MeSH
- tkáňové extrakty MeSH
- Check Tag
- myši MeSH
- MeSH
- buněčná diferenciace účinky léků MeSH
- fluorescenční protilátková technika MeSH
- inhibitory reverzní transkriptasy terapeutické užití MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory štítné žlázy metabolismus patologie terapie MeSH
- nevirapin terapeutické užití MeSH
- papilární karcinom metabolismus patologie terapie MeSH
- radioizotopy jodu farmakokinetika terapeutické užití MeSH
- senioři MeSH
- štítná žláza cytologie metabolismus účinky léků MeSH
- thyreoglobulin analýza MeSH
- tyreoidektomie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
PURPOSE: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. METHODS: The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). RESULTS: Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. CONCLUSIONS: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.
- MeSH
- analýza přežití MeSH
- biologické modely MeSH
- nádory farmakoterapie patofyziologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakokinetika farmakologie MeSH
- radiofarmaka farmakokinetika farmakologie MeSH
- radioizotopy fosforu farmakokinetika farmakologie MeSH
- radioizotopy jodu farmakokinetika farmakologie MeSH
- viabilita buněk účinky léků fyziologie MeSH
- vztah dávky záření a odpovědi MeSH
- yterbium farmakokinetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The absence of high-affinity potassium uptake in Candida glabrata, the consequence of the deletion of the TRK1 gene encoding the sole potassium-specific transporter, has a pleiotropic effect. Here, we show that in addition to changes in basic physiological parameters (e.g., membrane potential and intracellular pH) and decreased tolerance to various cell stresses, the loss of high affinity potassium uptake also alters cell-surface properties, such as an increased hydrophobicity and adherence capacity. The loss of an efficient potassium uptake system results in diminished virulence as assessed by two insect host models, Drosophila melanogaster and Galleria mellonella, and experiments with macrophages. Macrophages kill trk1Δ cells more effectively than wild type cells. Consistently, macrophages accrue less damage when co-cultured with trk1Δ mutant cells compared to wild-type cells. We further show that low levels of potassium in the environment increase the adherence of C. glabrata cells to polystyrene and the propensity of C. glabrata cells to form biofilms.
- MeSH
- biofilmy růst a vývoj MeSH
- buněčná adheze fyziologie MeSH
- buněčná membrána metabolismus MeSH
- buněčné linie MeSH
- Candida glabrata genetika metabolismus patogenita MeSH
- draslík metabolismus MeSH
- draslíko-vodíkové antiportéry genetika MeSH
- Drosophila melanogaster mikrobiologie MeSH
- hydrofobní a hydrofilní interakce MeSH
- iontový transport MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- membránové potenciály fyziologie MeSH
- můry mikrobiologie MeSH
- povrchové vlastnosti MeSH
- proteiny přenášející kationty genetika MeSH
- regulace genové exprese u hub genetika MeSH
- THP-1 buňky MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
