In vivo and in vitro effects of RAD001 on bladder cancer

Objective: To evaluate the influence of Everolimus (RAD001) on chemically induced urothelial lesions in mice and its influence on in vitro human bladder cancer cell lines. Methods: ICR male mice were given N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for a period of 12 weeks. Subsequently, RAD001 was administered via oral gavage, for 6 weeks. At the end of the experiment, all the animals were sacrificed and tumor development was determined by means of histopathologic evaluation; mammalian target of rapamycin (mTOR) expressivity was evaluated by immunohistochemistry. Three human bladder cancer cell lines (T24, HT1376, and 5637) were treated using a range of RAD001 concentrations. MTT assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to assess cell proliferation, apoptosis index, and cell cycle analysis, respectively. Immunoblotting analysis of 3 cell line extracts using mTOR and Akt antibodies was performed in order to study the expression of Akt and mTOR proteins and their phosphorylated forms. Results: The incidence of urothelial lesions in animals treated with RAD001 was similar to those animals not treated. RAD001 did not block T24 and HT1376 cell proliferation or induce apoptosis. A reduction in cell proliferation rate and therefore G0/G1 phase arrest, as well as a statistically significant induction of apoptosis (P 0.001), was only observed in the 5637 cell line. Conclusion: RAD001 seems not to have a significant effect on chemically induced murine bladder tumors. The effect of RAD001 on tumor proliferation and apoptosis was achieved only in superficial derived bladder cancer cell line, no effect was observed in invasive cell lines.

Desvio de posicionamento em radioterapia para patologias de cabeça e pescoço e próstata: revisão de literatura

Introdução – Numa era em que os tratamentos de Radioterapia Externa (RTE) exigem cada vez mais precisão, a utilização de imagem médica permitirá medir, quantificar e avaliar o impacto do erro provocado pela execução do tratamento ou pelos movimentos dos órgãos. Objetivo – Analisar os dados existentes na literatura acerca de desvios de posicionamento (DP) em patologias de cabeça e pescoço (CP) e próstata, medidos com Cone Beam Computed Tomography (CBCT) ou Electronic Portal Image Device (EPID). Metodologia – Para esta revisão da literatura foram pesquisados artigos recorrendo às bases de dados MEDLINE/PubMed e b-on. Foram incluídos artigos que reportassem DP em patologias CP e próstata medidos através de CBCT e EPID. Seguidamente foram aplicados critérios de validação, que permitiram a seleção dos estudos. Resultados – Após a análise de 35 artigos foram incluídos 13 estudos e validados 9 estudos. Para tumores CP, a média (μ) dos DP encontra-se entre 0,0 e 1,2mm, com um desvio padrão (σ) máximo de 1,3mm. Para patologias de próstata observa-se μDP compreendido entre 0,0 e 7,1mm, com σ máximo de 7,5mm. Discussão/Conclusão – Os DP em patologias CP são atribuídos, maioritariamente, aos efeitos secundários da RTE, como mucosite e dor, que afetam a deglutição e conduzem ao emagrecimento, contribuindo para a instabilidade da posição do doente durante o tratamento, aumentando as incertezas de posicionamento. Os movimentos da próstata devem-se principalmente às variações de preenchimento vesical, retal e gás intestinal. O desconhecimento dos DP afeta negativamente a precisão da RTE. É importante detetá-los e quantificá-los para calcular margens adequadas e a magnitude dos erros, aumentando a precisão da administração de RTE, incluindo o aumento da segurança do doente. - ABSTRACT - Background and Purpose – In an era where precision is an increasing necessity in external radiotherapy (RT), modern medical imaging techniques provide means for measuring, quantifying and evaluating the impact of treatment execution and movement error. The aim of this paper is to review the current literature on the quantification of setup deviations (SD) in patients with head and neck (H&N) or prostate tumors, using Cone Beam Computed Tomography (CBCT) or Electronic Portal Image Device (EPID). Methods – According to the study protocol, MEDLINE/PubMed and b-on databases were searched for trials, which were analyzed using selection criteria based on the quality of the articles. Results – After assessment of 35 papers, 13 studies were included in this analysis and nine were authenticated (6 for prostate and 3 for H&N tumors). The SD in the treatment of H&N cancer patients is in the interval of 0.1 to 1.2mm, whereas in prostate cancer this interval is 0.0 to 7.1mm. Discussion – The reproducibility of patient positioning is the biggest barrier for higher precision in RT, which is affected by geometrical uncertainty, positioning errors and inter or intra-fraction organ movement. There are random and systematic errors associated to patient positioning, introduced since the treatment planning phase or through physiological organ movement. Conclusion – The H&N SD are mostly assigned to the Radiotherapy adverse effects, like mucositis and pain, which affect swallowing and decrease secretions, contributing for the instability of patient positioning during RT treatment and increasing positioning uncertainties. Prostate motion is mainly related to the variation in bladder and rectal filling. Ignoring SD affects negatively the accuracy of RT. Therefore, detection and quantification of SD is crucial in order to calculate appropriate margins, the magnitude of error and to improve accuracy in RTE and patient safety.

Comparison of the pencil beam convolution algorithm and the analytical anisotropic algorithm in breast tumors

The calculation of the dose is one of the key steps in radiotherapy planning1-5. This calculation should be as accurate as possible, and over the years it became feasible through the implementation of new algorithms to calculate the dose on the treatment planning systems applied in radiotherapy. When a breast tumour is irradiated, it is fundamental a precise dose distribution to ensure the planning target volume (PTV) coverage and prevent skin complications. Some investigations, using breast cases, showed that the pencil beam convolution algorithm (PBC) overestimates the dose in the PTV and in the proximal region of the ipsilateral lung. However, underestimates the dose in the distal region of the ipsilateral lung, when compared with analytical anisotropic algorithm (AAA). With this study we aim to compare the performance in breast tumors of the PBC and AAA algorithms.