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- Application of gold nanoparticles as radiosensitizer for metastatic prostate cancer cell linesPublication . Soares, Sílvia; Faria, Isabel; Aires, Fátima; Monteiro, Armanda; Pinto, Gabriela; Sales, Maria Goreti; Correa-Duarte, Miguel A.; Guerreiro, Susana G.; Fernandes, RúbenMore than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.
- Digital skills of therapeutic radiographers/radiation therapists – Document analysis for a European educational curriculumPublication . Barbosa, B.; Bravo, I.; Oliveira, C.; Antunes, L.; Couto, J. G.; McFadden, S.; Hughes, C.; McClure, P.; Dias, A. G.It is estimated that around 50% of cancer patients require Radiotherapy (RT) at some point during their treatment, hence Therapeutic Radiographers/Radiation Therapists (TR/RTTs) have a key role to play in patient management. It is essential for TR/RTTs to keep abreast with new technologies and continuously develop the digital skills necessary for safe RT practice. The RT profession and education is not regulated at European Union level, which leads to heterogeneity in the skills developed and practised among countries. This study aimed to explore the white and grey literature to collate data on the relevant digital skills required for TR/RTTs practice.
- Clinical validation of a graphical method for radiation therapy plan quality assessmentPublication . Ventura, Tiago; Dias, Joana; Khouri, Leila; Netto, Eduardo; Soares, André; Costa Ferreira, Brigida; Rocha, Humberto; Lopes, Maria do CarmoBackground: This work aims at clinically validating a graphical tool developed for treatment plan assessment, named SPIDERplan, by comparing the plan choices based on its scoring with the radiation oncologists (RO) clinical preferences. Methods: SPIDERplan validation was performed for nasopharynx pathology in two steps. In the first step, three ROs from three Portuguese radiotherapy departments were asked to blindly evaluate and rank the dose distributions of twenty pairs of treatment plans. For plan ranking, the best plan from each pair was selected. For plan evaluation, the qualitative classification of ‘Good’, ‘Admissible with minor deviations’ and ‘Not Admissible’ were assigned to each plan. In the second step, SPIDERplan was applied to the same twenty patient cases. The tool was configured for two sets of structures groups: the local clinical set and the groups of structures suggested in international guidelines for nasopharynx cancer. Group weights, quantifying the importance of each group and incorporated in SPIDERplan, were defined according to RO clinical preferences and determined automatically by applying a mixed linear programming model for implicit elicitation of preferences. Intra- and inter-rater ROs plan selection and evaluation were assessed using Brennan-Prediger kappa coefficient. Results: Two-thirds of the plans were qualitatively evaluated by the ROs as ‘Good’. Concerning intra- and inter-rater variabilities of plan selection, fair agreements were obtained for most of the ROs. For plan evaluation, substantial agreements were verified in most cases. The choice of the best plan made by SPIDERplan was identical for all sets of groups and, in most cases, agreed with RO plan selection. Differences between RO choice and SPIDERplan analysis only occurred in cases for which the score differences between the plans was very low. A score difference threshold of 0.005 was defined as the value below which two plans are considered of equivalent quality. Conclusion: Generally, SPIDERplan response successfully reproduced the ROs plan selection. SPIDERplan assessment performance can represent clinical preferences based either on manual or automatic group weight assignment. For nasopharynx cases, SPIDERplan was robust in terms of the definitions of structure groups, being able to support different configurations without losing accuracy.
- Adipocyte secretome increases radioresistance of malignant melanocytes by improving cell survival and decreasing oxidative statusPublication . Coelho, Pedro; Silva, Liliana; Faria, Isabel; Vieira, Mónica; Monteiro, Armanda; Pinto, Gabriela; Prudêncio, Cristina; Fernandes, Rúben; Soares, RaquelRadiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenoyype of these cells with a concomitant activation of the AKT signaling pathway These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.
- The influence of miRNAs on radiotherapy treatment in prostate cancer – a systematic reviewPublication . Soares, Sílvia; Guerreiro, Susana S.; Cruz-Martins, Natália; Sousa Pinho Faria, Isabel Maria; Baylina, Pilar; Sales, Maria Goretti; Correa-Duarte, Miguel A.; Fernandes, RúbenIn the last years, extensive investigation on miRNomics have shown to have great advantages in cancer personalized medicine regarding diagnosis, treatment and even clinical outcomes. Prostate cancer (PCa) is the second most common male cancer and about 50% of all PCa patients received radiotherapy (RT), despite some of them develop radioresistance. Here, we aim to provide an overview on the mechanisms of miRNA biogenesis and to discuss the functional impact of miRNAs on PCa under radiation response. As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. Identification of miRNAs panel can be thus considered an upcoming and potentially useful strategy in PCa diagnosis, given that radioresistance biomarkers, in both prognosis and therapy still remains a challenge.
- Compliance to radiation therapy of head and neck cancer patients and impact on treatment outcomePublication . Costa Ferreira, Brigida; Sá-Couto, P.; Lopes, M. C.; Khouri, L.The aims of the study were to evaluate head and neck cancer (HNC) patient's compliance to the planned radiation therapy (RT) using the department policy established in 2005 at IPOCFG and to estimate the impact on treatment outcome due to failure in receiving RT as prescribed.
- Comparison of two beam angular optimization algorithms guided by automated multicriterial IMRTPublication . Ventura, Tiago; Rocha, Humberto; Costa Ferreira, Brigida; Dias, Joana; Lopes, Maria do CarmoTo compare two beam angle optimization (BAO) algorithms for coplanar and non-coplanar geometries in a multicriterial optimization framework.
- Treatment failure prediction for head-and-neck cancer radiation therapyPublication . Rocha, H.; Khouri, L.; Lopes, M.C.; Dias, J.; Ferreira, BrigidaTreatment outcome prediction is an important emerging topic in oncologic care. To support radiation oncologists on their decisions, with individualized, tailored treatment regimens increasingly becoming the standard of care, accurate tools to predict tumour response to treatment are needed. The goal of this work is to identify the most determinant factor(s) for treatment response aiming to develop prediction models that robustly estimate tumour response to radiation therapy in patients with head- and-neck cancer.
- Biological dose-escalated definitive radiation therapy in head and neck cancerPublication . Costa Ferreira, Brigida; Sá-Couto, Pedro; Khouri, Leila; Lopes, Maria do CarmoTo compare treatment outcome of patients with head and neck (HN) tumours treated with definitive radiation therapy that, mainly owing to differences in the fractionation scheme used with simultaneous integrated boost techniques, resulted in a different biological dose.
- Vitamin A Enhances Macrophages Activity Against B16-F10 Malignant Melanocytes: A New Player for Cancer Immunotherapy?Publication . Oliveira, Sofia; Costa, José; Faria, Isabel; Guerreiro, Susana G; Fernandes, RúbenBackground and objectives: The incidence of cutaneous melanoma has been increasing. Melanoma is an aggressive form of skin cancer irresponsive to radiation and chemotherapy, rendering this cancer a disease with poor prognosis: In order to surpass some of the limitations addressed to melanoma treatment, alternatives like vitamins have been investigated. In the present study, we address this relationship and investigate the possible role of vitamin A. Materials and Methods: We perform a co-culture assay using a macrophage cell model and RAW 264.7 from mouse, and also a murine melanoma cell line B16-F10. Macrophages were stimulated with both Escherichia coli lipopolysaccharides (LPS) as control, and also with LPS plus vitamin A. Results: Using B16-F10 and RAW 264.7 cell lines, we were able to demonstrate that low concentrations of vitamin A increase cytotoxic activity of macrophages, whereas higher concentrations have the opposite effect. Conclusion: These findings can constitute a new point of view related to immunostimulation by nutrients, which may be considered one major preventive strategy by enhancing the natural defense system of the body.
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