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Dublin, Ireland

Murray J.,Institute of Technology Sligo | Gannon S.,Focas Institute | Rawe S.,Dublin Institute of Technology | Murphy J.E.J.,Institute of Technology Sligo
Anticancer Research

Background/Aim: Hypoxia can affect chemo-therapeutic drug efficacy in cancer patients, yet related in vitro assays in oxygen-rich environment remain the norm. Such levels are well beyond normoxic/hypoxic levels typically experienced by normal tissues/tumor masses. The present study evaluated how artesunate anti-tumor efficacy is modulated by oxygen availability in HeLa cells and its implications for future in vitro analyses. Materials and Methods: Real-time cell analysis was employed to evaluate HeLa cell toxicity to artesunate at 21%, 4% or 1% oxygen. Cell count analysis was performed to validate real-time data. Results: An increase in artesunate efficacy was observed when oxygen concentration was reduced from atmospheric levels down to in vivo-relevant levels. Conclusion: Artesunate is more potent than originally reported using standard oxygen conditions during in vitro studies. The inclusion of this long overlooked variable as standard in future in vitro analysis procedures is warranted. Source

Chandra S.,Focas Institute | Doran J.,Focas Institute | McCormack S.J.,Trinity College Dublin | Kennedy M.,Focas Institute | Chatten A.J.,Imperial College London
Solar Energy Materials and Solar Cells

Plasmonic excitation enhanced fluorescence of CdSe/ZnS core-shell quantum dots (QDs) in the presence of Au nanoparticles (NPs) has been studied for application in quantum dot solar concentrator (QDSC) devices. We observe that there is an optimal concentration of Au NPs that gives a maximum 53% fluorescence emission enhancement for the particular QD/Au NP composite studied. The optimal concentration depends on the coupling and spacing between neighboring QDs and Au NPs. We show the continuous transition from fluorescence enhancement to quenching, depending on Au NP concentration. The locally enhanced electromagnetic field induced by the surface plasmon resonance in the Au NPs leads to an increased excitation rate for the QDs. This is evidenced by excitation wavelength dependent fluorescence enhancement, where the locally enhanced field around the Au NPs is more pronounced close to the surface plasmon resonance (SPR) wavelength. However, at higher concentrations of Au NPs non-radiative energy transfer from the QDs to the Au NPs particles leads to a decrease of the emission, which is confirmed by detection of both a double exponential lifetime decay in, and a decrease in the lifetime of the QDs. The overall fluorescence emission enhancement depends on these competing effects; increased excitation rate and non-radiative energy transfer. © 2011 Elsevier B.V. All rights reserved. Source

Zanchetta L.M.,Institute of Technology Sligo | Garcia A.,Focas Institute | Lyng F.,Focas Institute | Walsh J.,Dublin Institute of Technology | Murphy J.E.J.,Institute of Technology Sligo
International Journal of Radiation Biology

Purpose: To assess changes in mitochondrial morphology and mitophagy induced by simulated sunlight irradiation (SSI) and how these changes are modulated by mitochondrial activity and energy source. Materials and methods: Human malignant amelanotic melanoma A375 cells were pre-treated with either a mitochondrial activity enhancer, uncoupler or were either melanin or glutamine supplemented/starved for 4 hours pre-exposure to sunlight. A Q-Sun Solar Simulator (Q-Lab, Homestead, FL, USA) was employed to expose cells to simulated sunlight. Confocal microscopy imaging of A375 cells co-loaded with mitochondria and lysosome-specific fluorescent dyes was used to identify these organelles and predict mitophagic events. Results: SSI induces pronounced changes in mitochondrial dynamics and mitophagy in exposed skin cells compared to control and these effects were modified by both glutamine and melanin. Conclusions: Mitochondrial dynamics and rate of mitophagy in melanoma cells are sensitive to even short bursts of environmentally relevant SSI. Mitochondrial dynamics, and its modulation, may also play a role in mitophagy regulation, cell survival and proliferation post SSI. © 2011 Informa UK, Ltd. Source

Shields L.,St Lukes Hospital | Shields L.,University College Dublin | Vega-Carrascal I.,Focas Institute | Lyng F.M.,Focas Institute | And 3 more authors.
Radiation Research

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells is not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant increase in γ-H2AX foci formation when irradiated to 20 cGy in-field in comparison to out-of-field. However, no significant difference in cell survival or colony volume was observed whether the PNT1A cells were irradiated in-field or out-of-field. Out-of-field radiation dose alone can have a damaging effect on the proliferation of PNT1A cells when a clinically relevant dose of 2 Gy is delivered in in-field. Out-of-field radiation with the transfer of bystander factors induces an adaptive response in the PNT1A cells. © 2014 by Radiation Research Society. Source

Zanchetta L.M.,Institute of Technology Sligo | Zanchetta L.M.,Focas Institute | Kirk D.,Focas Institute | Lyng F.,Focas Institute | And 2 more authors.
Photodermatology Photoimmunology and Photomedicine

Background: Solar ultraviolet radiation (UVR) is the principal etiological factor in skin carcinogenesis. In vivo and in vitro studies have demonstrated previously that oxidative DNA damage, mitochondrial mass and mitochondrial membrane potential (MMP) changes are associated with skin cell response to UVR stress.Methods: Spontaneously immortalized human skin keratinocytes were irradiated with increasing sub-lethal doses of simulated sunlight irradiation (SSI) using a Q-Sun solar simulator. The effects of SSI on reactive oxygen species (ROS) formation, mitochondrial mass and MMP were then determined.Results: SSI induced mitochondrial mass increase post low SSI (0.25-2.5 J/cm2), whereas higher SSI doses (5.0 and 7.5 J/cm2) decreased mitochondrial mass. Mitochondrial mass increased with time post 5.0 J/cm2 irradiation and all changes in mass were independent of cell density status. Changes in ROS and MMP were cell density dependent. Additionally, an inverted dose-dependent decrease in ROS formation was observed 3 h post SSI with the lower SSI dose (0.25 J/cm2).Conclusions: Observations from the present study suggest that changes in the cell's microenvironment (modeled through varying cell density) influence changes in MMP and ROS detoxifying responses in sun-exposed skin cells. © 2010 John Wiley & Sons A/S. Source

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