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- 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.
- Advantage of beam angle optimization in head-and-neck IMRT: Patient specific analysisPublication . Ventura, Tiago; Lopes, Maria do Carmo; Rocha, Humberto; Costa Ferreira, Brígida; Dias, JoanaRadiation therapy (RT) main purpose is to eliminate, in a controlled way, all tumor cells sparing as much as possible the normal tissues. Intensity Modulated Radiation Therapy (IMRT) is becoming the standard treatment technique in RT. Beam angle optimization (BAO) has potential to confer more quality to IMRT inverse planning process compared to manual trial and error approaches. In this study, the BAO advantages in head-and-neck patients are highlighted, using a patient specific analysis. Fluence optimization was done with Erasmus-iCycle multicriterial engine and BAO optimization was performed using two different algorithms: a combinatorial iterative algorithm and an algorithm based on a pattern search method. Plan assessment and comparison was performed with the graphical tool SPIDERplan. Among a set of forty studied nasopharynx cancer cases, three patients have been select for the specific analysis presented in this work. BAO presented plan quality improvements when beam angular optimized plans were compared with the equidistant beam angle solution and when plans based on non-coplanar beams geometries were compared with coplanar arrangements. Improvement in plan quality with a reduced number of beams was also achieved, in one case. For all cases, BAO generated plans with higher target coverage and better sparing of the normal tissues
- Analyses of pharyngeal constrictor muscles doses in radiotherapy of head and neck cancer patientsPublication . Guerra, Jéssica; Khouri, Leila; Ferreira, BrigidaLate dysphagia is a radiotherapy (RT) side-effect that may develop up to 3 years after treatment and could be related to the irradiation of the Pharyngeal Constrictor Muscles (PCM) in RT. To quantify the radiation dose delivered to the PCM in head and neck (H&N) cancer patients with and without dysphagia.
- Analysis of the cochlear dose in head and neck cancer radiotherapyPublication . Afonso, Jennifer; Khouri, Leila; Ferreira, BrigidaInternal hearing damage induced by radiotherapy (RT) can lead to sensorineural hearing loss (hypoacusia) due tumor’s proximity with the auditory apparatus. Furthermore, the concurrent use of RT with chemotherapy (cisplatin) is known to increase toxicity. To quantify the radiation dose delivered to the (ipsilateral and contralateral) cochlea in head and neck cancer patients with and without hypoacusia.
- Apparent diffusion coefficient in the analysis of prostate cancerPublication . Adubeiro, Nuno; Nogueira, Luísa; Ribeiro, Eduardo; Alves, Sandra; Ferreira, Hugo; La Fuente, JoséThe multiparametric magnetic resonance imaging (MPMRI) approach, has allowed the diagnostic performance in the detection and characterization of prostate cancer (PCa). Diffusion-weighted imaging (DWI), is an important technique in the MPMRI, that provides qualitative and quantitative biological information regarding water diffusivity in a non-invasive manner. The apparent diffusion coefficient (ADC) measures water mobility and can be quantified from the signal intensity loss between two or more b-values. Different studies reported that ADC values are directly associated with microvessel density and cellularity. One of the main aspects that is in discussion is the b-values that must be used in the DWI sequence in order to compute ADC.
- 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.
- Automated fluence map optimization based on fuzzy inference systemsPublication . Dias, Joana; Rocha, Humberto; Ventura, Tiago; BC Ferreira; Lopes, Maria do CarmoThe planning of an intensity modulated radiation therapy treatment requires the optimization of the fluence intensities. The fluence map optimization (FMO) is many times based on a nonlinear continuous programming problem, being necessary for the planner to define a priori weights and/or lower bounds that are iteratively changed within a trial-and-error procedure until an acceptable plan is reached. In this work, the authors describe an alternative approach for FMO that releases the human planner from trial-and-error procedures, contributing for the automation of the planning process.
- Automated Radiotherapy Treatment Planning Using Fuzzy Inference SystemsPublication . Dias, Joana; Rocha, Humberto; Ventura, Tiago; Costa Ferreira, Brigida; Lopes, Maria do CarmoRadiotherapy is one of the treatments available for cancer patients, aiming to irradiate the tumor while preserving healthy structures. The planning of a treatment is a lengthy trial and error procedure, where treatment parameters are iteratively changed and the delivered dose is calculated to see whether it complies with the desired medical prescription. In this paper, a procedure based on fuzzy inference systems (FIS) for automated treatment planning is developed, allowing the calculation of high quality treatment plans without requiring human intervention. The procedure is structured in two different phases, incorporating the automatic selection of the best set of equidistant beam irradiation directions by an enumeration procedure. The developed method is extensively tested using ten head-and-neck cancer cases.
- Beam angle optimization in IMRT: are we really optimizing what matters?Publication . Rocha, Humberto; Dias, Joana Matos; Ventura, Tiago; BC Ferreira; Lopes, Maria do CarmoIntensity‐modulated radiation therapy (IMRT) is a modern radiotherapy modality that uses a multileaf collimator to enable the irradiation of the patient with nonuniform maps of radiation from a set of distinct beam irradiation directions. The aim of IMRT is to eradicate all cancerous cells by irradiating the tumor with a prescribed dose while simultaneously sparing, as much as possible, the neighboring tissues and organs. The optimal choice of beam irradiation directions—beam angle optimization (BAO)—can play an important role in IMRT treatment planning by improving organ sparing and tumor coverage, increasing the treatment plan quality. Typically, the BAO search is guided by the optimal value of the fluence map optimization (FMO)—the problem of obtaining the most appropriate radiation intensities for each beam direction. In this paper, a new score to guide the BAO search is introduced and embedded in a parallel multistart derivative‐free optimization framework that is detailed for the extremely challenging continuous BAO problem. For the set of 10 clinical nasopharyngeal tumor cases considered, treatment plans obtained for optimized beam directions clearly outperform the benchmark treatment plans obtained considering equidistant beam directions typically used in clinical practice. Furthermore, treatment plans obtained considering the proposed score clearly improve the quality of the plans resulting from the use of the optimal value of the FMO problem to guide the BAO search.
- 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.