Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, in vitro

<p>Abstract</p> <p>Background</p> <p>Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitising and cell cycle effects.</p> <p>Methods</p> <p>Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.</p> <p>Results</p> <p>Vinflunine and vinorelbine induced a comparable radiosensitising effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.</p> <p>Conclusion</p> <p>The radiosensitising effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitising effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.</p

The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein.

BACKGROUND: Regions within solid tumours often experience oxygen deprivation, which is associated with resistance to chemotherapy and irradiation. The aim of this study was to evaluate the radiosensitising effect of gemcitabine and its main metabolite dFdU under normoxia versus hypoxia and to determine whether hypoxia-inducible factor 1 (HIF-1) is involved in the radiosensitising mechanism. METHODS: Stable expression of dominant negative HIF-1α (dnHIF) in MDA-MB-231 breast cancer cells, that ablated endogenous HIF-1 transcriptional activity, was validated by western blot and functionality was assessed by HIF-1α activity assay. Cells were exposed to varying oxygen environments and treated with gemcitabine or dFdU for 24 h, followed by irradiation. Clonogenicity was then assessed. Using radiosensitising conditions, cells were collected for cell cycle analysis. RESULTS: HIF-1 activity was significantly inhibited in cells stably expressing dnHIF. A clear radiosensitising effect under normoxia and hypoxia was observed for both gemcitabine and dFdU. No significant difference in radiobiological parameters between HIF-1 proficient and HIF-1 deficient MDA-MB-231 cells was demonstrated. CONCLUSIONS: For the first time, radiosensitisation by dFdU, the main metabolite of gemcitabine, was demonstrated under low oxygen conditions. No major role for functional HIF-1 protein in radiosensitisation by gemcitabine or dFdU could be shown

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells

<p>Abstract</p> <p>Background</p> <p>Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This <it>in vitro </it>study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.</p> <p>Methods</p> <p>The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells. Using simultaneous or sequential exposure schedules, the cytotoxicity and radiosensitising effect of 24 h MTA combined with 1 h or 24 h dFdC were analysed.</p> <p>Results</p> <p>Including a time interval between MTA exposure and irradiation seemed favourable to MTA immediately preceding or following radiotherapy. MTA induced a significant S phase accumulation that persisted for more than 8 h after drug removal. Among different MTA/dFdC combinations tested, the highest synergistic interaction was produced by 24 h MTA followed by 1 h dFdC. Combined with irradiation, this schedule showed a clear radiosensitising effect.</p> <p>Conclusions</p> <p>Results from our <it>in vitro </it>model suggest that the sequence 24 h MTA → 1 h dFdC → RT is the most rational design and would, after confirmation in an <it>in vivo </it>setting, possibly provide the greatest benefit in the clinic.</p

Pensamiento crítico en estudiantes del Grado de Educación Social

El presente artículo se centra en una investigación cualitativa sobre las creencias acerca del pensamiento crítico que poseen 72 estudiantes de tercer curso del Grado de Educación Social de la Universidad de Huelva (España). Los resultados, en consonancia con otras investigaciones, muestran que el alumnado tiene un conocimiento poco detallado aunque certero de lo que significa dicha competencia, ofreciendo explicaciones generales que van en acuerdo con las ideas que tienen acerca de la Universidad, la Sociedad y la finalidad de la Educación Social. La buena disposición que muestra la mayoría del alumnado investigado choca con escasos hábitos para el pensamiento crítico, achacándolo a una formación reproductiva, a la influencia perniciosa de determinados poderes sociales y a un no-saber-hacer-y-actuar de los futuros educadores sociales.This article focuses on qualitative research on the beliefs about critical thinking held by 72 third year students of the Social Education Degree of the University of Huelva (Spain). The results show that the students have a little detailed but accurate knowledge of what this competence means, offering general explanations that are in line with the ideas they have about the University, Society and the purpose of Social Education. The willingness shown by the majority of the students researched clashes with scarce habits for critical thinking, blaming it on reproductive training, the pernicious influence of certain social powers and the non-know-how-to-act of future social educators