RESUMO
The caspase-3-cleaved presence was evaluated in this study in the heart of irradiated rats, during the decline of ventricular function. Female Wistar rats were irradiated with a single dose of radiation (15 Gy) delivered directly to the heart and the molecular, histological and physiological evaluations were performed at thirteen months post-irradiation. The expressions of procollagen type I, TGF-ß1 and caspase-3-cleaved were analyzed using Western blotting. Cardiac structural and functional alterations were investigated by echocardiography and electron microscopy. In the irradiated group, the levels of procollagen type I, TGF-ß1 and caspase-3-cleaved are increased. Significant histological changes (degeneration of heart tissue and collagen deposition) and functional (reduced ejection fraction) were observed. Data suggest that the cardiac function decline after exposure to ionizing radiation is related, in part, to increased collagen and increased caspase-3-cleaved.
Assuntos
Caspase 3/metabolismo , Colágeno Tipo I/metabolismo , Coração/efeitos da radiação , Miocárdio/enzimologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Western Blotting , Relação Dose-Resposta à Radiação , Ecocardiografia , Ativação Enzimática/efeitos da radiação , Feminino , Microscopia Eletrônica de Transmissão , Miocárdio/ultraestrutura , Ratos , Ratos WistarRESUMO
Purpose: Technological advancement in the treatment of cancer together with early detection and diagnosis have considerably improved the survival of breast cancer patients. On the other hand, the potential of patients developing side effects from cancer treatment are not negligible. Despite the progress that has been made in terms of early diagnosis, therapy, and survival, including improvements in the chemotherapeutic agents, radiation and molecular targeted therapies, cardiotoxicity of cancer therapy is still cause for concern. Radiation therapy for breast cancer is associated with increased risk of heart disease and myocardial infarction. Furthermore, the association of radiation therapy to chemotherapy is an important aspect to be considered in the development of cardiac disease, as this could play an additional role as a risk factor. Besides the heart effect, other side effects can be observed in the bone, ovary, uteri, and other organs. This paper aims to review the recent literature to present the current understanding of side effects associated with breast cancer treatment. The focus is on recent preclinical studies that have assessed potential changes in different organs that may be injured after breast cancer treatment, both due to both radiation and chemotherapy agents.Conclusion: Radiation-induced heart disease is one important side effect that must be considered during the treatment planning and patient follow-up. The cardiac damage can be potentialized when chemotherapy is associated to radiotherapy, and the literature findings indicate that heart fibrosis plays an important role at the radio-chemotherapy induced cardiac damage. Literature findings also showed important side effects at the bone, that can lead to ospeoporosis, due to the decrease of calcium, after radio or chemotherapy treatments. This decrease could be explained by the ovarian failure observed at rats after chemotherapy treatment. It is of great importance to acknowledge the complications originating from the treatment, so that new strategies can be developed. In this way, it will be possible to minimize side effects and improve the patients' quality of life.
Assuntos
Neoplasias da Mama/terapia , Animais , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapiaRESUMO
Monte Carlo calculations of the absorbed dose at various points of a brachytherapy anthropomorphic phantom are presented. The phantom walls and internal structures are made of polymethylmethacrylate and its external shape was taken from a female Alderson phantom. A complete Fletcher-Green type applicator with the uterine tandem was fixed at the bottom of the phantom reproducing a typical geometrical configuration as that attained in a gynecological brachytherapy treatment. The dose rate produced by an array of five (137)Cs CDC-J type sources placed in the applicator colpostats and the uterine tandem was evaluated by Monte Carlo simulations using the code PENELOPE at three points: point A, the rectum, and the bladder. The influence of the applicator in the dose rate was evaluated by comparing Monte Carlo simulations of the sources alone and the sources inserted in the applicator. Differences up to 56% in the dose may be observed for the two cases in the planes including the rectum and bladder. The results show a reduction of the dose of 15.6%, 14.0%, and 5.6% in the rectum, bladder, and point A respectively, when the applicator wall and shieldings are considered.
Assuntos
Braquiterapia/instrumentação , Método de Monte Carlo , Pelve/efeitos da radiação , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/instrumentação , Braquiterapia/métodos , Braquiterapia/estatística & dados numéricos , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Radioterapia Conformacional/instrumentação , Radioterapia Conformacional/métodos , Radioterapia Conformacional/estatística & dados numéricosRESUMO
Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use.
Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Glucuronidase/antagonistas & inibidores , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/tratamento farmacológico , Aptâmeros de Nucleotídeos/sangue , Aptâmeros de Nucleotídeos/metabolismo , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Regulação Neoplásica da Expressão Gênica , Glucuronidase/metabolismo , Humanos , Neoplasias Bucais/enzimologia , Neoplasias Bucais/patologia , Invasividade NeoplásicaRESUMO
This article presents the technical conditions necessary to establish appropriate radiation qualities for the calibration of the dosemeters used in the mammography detectors in the Laboratório de Ciências Radiológicas (LCR) from the Universidade do Estado do Rio de Janeiro. Tests were conducted to evaluate the homogeneity of the radiation field, scattering, half-value layers and system stability. The calibration method (substitution) is described in this work. A moderate alteration in filtration makes it possible to maintain the half-value layers within the limits recommended. The results indicate the adequacy of the LCR laboratory for the calibration of the dosemeters in the radiation qualities for mammography with an expanded uncertainty in the best measurement capability of ± 1.8 % (k = 2).