Preliminary pre-clinical studies on the side effects of breast cancer treatment.

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.

Design, Synthesis, Experimental and Theoretical Characterization of a New Multitarget 2-Thienyl-N-Acylhydrazone Derivative.

Pulmonary arterial hypertension (PAH) is a chronic cardiovascular disease that displays inflammatory components, which contributes to the difficulty of adequate treatment with the available therapeutic arsenal. In this context, the N-acylhydrazone derivative LASSBio-1359 was previously described as a multitarget drug candidate able to revert the events associated with the progression of PAH in animal models. However, in spite of having a dual profile as PDE4 inhibitor and adenosine A2A receptor agonist, LASSBio-1359 does not present balanced potencies in the modulation of these two targets, which difficult its therapeutic use. In this paper, we describe the design concept of LASSBio-1835, a novel structural analogue of LASSBio-1359, planned by exploiting ring bioisosterism. Using X-ray powder diffraction, calorimetric techniques, and molecular modeling, we clearly indicate the presence of a preferred synperiplanar conformation at the amide function, which is fixed by an intramolecular 1,5-N∙∙∙S σ-hole intramolecular interaction. Moreover, the evaluation of LASSBio-1835 (4) as a PDE4 inhibitor and as an A2A agonist confirms it presents a more balanced dual profile, being considered a promising prototype for the treatment of PAH.

Synchrotron microtomography to evaluate effects of different polychemotherapy drugs on cortical bone structure.

PURPOSE: To determine the effects of different polychemotherapy drugs on cortical bone structure, the femur diaphysis of rats were treated with two different chemotherapy drugs, AC (doxorubicin + cyclophosphamide) and TC (docetaxel + cyclophosphamide), and evaluated by 3D morphological analysis using synchrotron radiation microtomography. MATERIALS AND METHODS: Wistar rats were classified into three groups. One group received doses of docetaxel and cyclophosphamide (G1) - TC regimen; a second group received doses of doxorubicin and cyclophosphamide (G2) - AC regimen; while a control group (G0) received no further treatment. 3D tomographic images of the rats' femurs were obtained at the SYRMEP (Synchrotron Radiation for Medical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy, using monochromatic X-rays with resolution of 9 µm. RESULTS: It could be shown that the treatment caused significant differences in morphological parameters measured from the 3D images of femur diaphysis of rats, among the studied groups, complementing a previous study using stereological methods, biochemistry and electron microscopy. CONCLUSIONS: Our results indicate that the same process of osteoporosis caused by advancing age might occur in young women treated with docetaxel + cyclophosphamide (TC) and doxorubicin + cyclophosphamide (AC). 3D microtomography was shown to be an outstanding technique for bone analysis.

Evaluation of rib microstructure in Wistar rats using SR-µCT after radiation therapy simulation for breast cancer.

A better understanding of biological interactions that occur after exposure to photon radiation is needed in order to optimize therapeutic regimens and facilitate development and strategies that decrease radiation-induced side effects in humans. In this work, ribs of Wistar rat submitted to radiotherapy simulation were imaged using synchrotron radiation computed microtomography at Elettra Synchrotron Laboratory in Trieste, Italy. Histomorphometric parameters were calculated directly from the 3D microtomographic images and showed significant differences between irradiated and non-irradiated groups.

Segmentation of synchrotron radiation micro-computed tomography images using energy minimization via graph cuts.

The research on applications of segmentation algorithms to Synchrotron Radiation X-Ray micro-Computed Tomography (SR-µCT) is an open problem, due to the interesting and well-known characteristics of SR images, such as the phase contrast effect. The Energy Minimization via Graph Cuts (EMvGC) algorithm represents state-of-art segmentation algorithm, presenting an enormous potential of application in SR-µCT imaging. We describe the application of the algorithm EMvGC with swap move for the segmentation of bone images acquired at the ELETTRA Laboratory (Trieste, Italy).

Phase contrast X-ray synchrotron imaging for assessing external and internal morphology of Rhodnius prolixus.

PhC-SR-µCT is a nondestructive technique that allows the microanatomical investigations and 3D images reconstructions. This technique is performed in blood sucker, Rhodnius prolixus--one of the most important insect vectors of Trypanosoma cruzi, ethiologic agent of Chagas' disease in Latin America--was able to provide excellent information about the microanatomy of the thorax and head allowing a new tool for further studies of development and physiology of triatomine by a non-invasive method of observation.

Estudo de perfil de espalhamento usando difração de raios X de amostras de sangue irradiadas / Study of X-ray diffraction scattering profiles in irradiated blood samples

O aumento nas aplicações das radiações ionizantes pode produzir exposição de pessoas e objetos a campos de radiação, onde a intensidade depende do tipo da fonte e da atividade desenvolvida. Nesse trabalho, perfis de espalhamento de amostras liofilizadas de plasma, matriz celular e sangue total foram estudados. Os perfis de espalhamento foram obtidos com um difratômetro de raios X Shiamadzu (XRD6000) no Laboratório de Instrumentação Nuclear, LIN/Coppe. As amostras foram irradiadas com valores de dose de 2cGy a 100cGy no Inca, no Rio de Janeiro, e todas as amostras de plasma, matriz celular e sangue total foram liofilizadas a -60ºC e 780 mmHg até completa eliminação de água. Os ângulos de espalhamento de 5º a 35º foram varridos em passos de 0,05º com tempo de integração de 3 segundos. Os perfis de espalhamento das amostras irradiadas foram comparados com os perfis de amostras não irradiada. Nesse estudo observou-se que os perfis das amostras de matriz celular e sangue total são bastante parecidos. O perfil de espalhamento do plasma é muito característico porque em adição ao primeiro e ao segundo pico essas amostras mostraram mais dois picos estreitos.Os valores de θ1 e θ2 das amostras de plasma irradiado são maiores que os obtidos pelas amostras de plasma não irradiado e os valores de θ1 e θ2 das amostras de matriz celular irradiada são menores que os obtidos pelas amostras de matriz celular não irradiada.

The increase in ionizing radiation (IR) applications can expose people and objects to radiation fields, where the intensity depends on the type of source and the activity. In this work, scattering profiles of lyophilized samples of plasma, cellular matrix and total blood were studied. The scattering profiles were obtained using a Shiamadzu X-Ray diffractometer (XRD 6000) at the Laboratório de Instrumentação Nuclear, LIN/Coppe. The samples were irradiated with doses of from 2cGy to 100cGy at Inca in Rio de Janeiro and all the samples of plasma, cellular matrix and total blood were lyophilized at -60ºC and 780 mmHg until the water was totally eliminated. Scanning involved scattering angles of from 5º to 35º in steps of 0.05º with an integration time of 3 seconds. The scattering profiles of the irradiated samples were compared with non-irradiated sample profiles. In this study it was observed that the cellular matrix and total blood sample profiles are similar. The scattering profile of plasma is very characteristic because in addition to the first and second peaks, these samples show two other narrow peaks. The 1 and 2 values of irradiated plasma samples are greater than non-irradiated ones and the 1 and 2 values of the irradiated cellular matrix samples are smaller than ones obtained using non-irradiated cellular matrix samples.