Elemental profiles in distant tissues during tumor progression.

BACKGROUND: Essential elements have functions in tumor progression by promoting protumoral cellular processes, such as proliferation, and migration, among others. Obtaining an understanding of how these elements relate to tumor progression processes is of great importance for research. Elemental profile studies in distant tissues, which can be modulated by tumor cells to promote metastasis, have not been sufficiently investigated. The main goal of this study is to evaluate multielemental distribution during tumor progression, focusing on tumor tissue and distant tissues that may be affected. METHODS: Tumor progression in vivo was simulated by inoculating C57BL/6 mice with Lewis Lung Carcinoma (LLC) cells. Samples of the primary tumor and distant tissues were collected during 5 weeks of tumor progression for the control and experimental (tumor-bearing) groups. The biological samples were analyzed using the synchrotron radiation X-Ray fluorescence technique. Data on the concentration of P, S, K, Ca, Mn, Fe, Cu, and Zn in the samples were obtained and statistically analyzed to evaluate the distribution of the elements during tumor progression in the primary tumor as well as distant tissues. RESULTS: It was possible to observe significant changes in the concentrations' distribution of P, S, K, Ca, Mn, Fe, and Cu in distant tissues caused by the presence of tumor cells. It was also possible to detect a greater similarity between tumor tissue (which has the lung as tissue of origin) and a tissue of non-origin, such as the liver, which is an unprecedented result. Moreover, changes in the distributions of concentrations were detected and studied over time for the different tissues analyzed, such as primary tumor, liver and lung, in Control and Tumor groups. CONCLUSIONS: Among other results, this paper could explore the modulation of distant tissues caused by the presence of a primary tumor. This could be achieved by the evaluation of several elements of known biological importance allowing the study of different biological processes involved in cancer. The role of essential elements as modulators of the tumor microenvironment is a relevant aspect of tumor progression and this work is a contribution to the field of tumoral metallomics.

Trace elements during primordial plexiform network formation in human cerebral organoids.

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

Evaluation of the radiotherapy treatment planning in the presence of a magnetic valve tissue expander.

The combination of radiotherapy treatments and breast reconstruction, using temporary tissue expanders, generates several concerns due to the presence of a magnetic valve inside the radiation field. The objective of this work is to evaluate a radiotherapy treatment planning for a patient using a tissue expander. Isodose curve maps, obtained using radiochromic films, were compared to the ones calculated with two different dose calculation algorithms of the Eclipse radiotherapy Treatment Planning System (TPS), considering the presence or absence of the heterogeneity. The TPS calculation considering the presence of the heterogeneity shows changes around 5% in the isodose curves when they were compared with the calculation without heterogeneity correction. This calculation did not take in account the real density value of the heterogeneity. This limitation was quantified to be around 10% in comparison with the TPS calculation and experimental measurements using the radiochromic film. These results show that the magnetic valve should be taken in account in dose calculations of the TPS. With respect to the AAA and Pencil Beam Convolution algorithms, when the calculation is compared with the real distribution, AAA presents a distribution more similar to experimental dose distribution.

Influence of the presence of tissue expanders on energy deposition for post-mastectomy radiotherapy.

An increasing number of studies have shown that post-mastectomy radiotherapy presents benefits associated with the patients survival and a significant fraction of the treated patients makes use of tissue expanders for breast reconstruction. Some models of tissue expanders have a magnetic disk on their surface that constitutes heterogeneity in the radiation field, which can affect the dose distribution during the radiotherapy treatment. In this study, the influence of a metallic heterogeneity positioned in a breast tissue expander was evaluated by means of Monte Carlo simulations using the MCNPX code and using Eclipse treatment planning system. Deposited energy values were calculated in structures which have clinical importance for the treatment. Additionally, the effect in the absorbed energy due to backscattering and attenuation of the incident beam caused by the heterogeneity, as well as due to the expansion of the prosthesis, was evaluated in target structures for a 6 MV photon beam by simulations. The dose distributions for a breast treatment were calculated using a convolution/superposition algorithm from the Eclipse treatment planning system. When compared with the smallest breast expander volume, underdosage of 7% was found for the largest volume of breast implant, in the case of frontal irradiation of the chest wall, by Monte Carlo simulations. No significant changes were found in dose distributions for the presence of the heterogeneity during the treatment planning of irradiation with an opposed pair of beams. Even considering the limitation of the treatment planning system, the results obtained with its use confirm those ones found by Monte Carlo simulations for a tangent beam irradiation. The presence of a heterogeneity didn't alters the dose distributions on treatment structures. The underdosage of 7% observed with Monte Carlo simulations were found for irradiation at 0°, not used frequently in a clinical routine.

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.

Synchrotron radiation X-ray microfluorescence reveals polarized distribution of atomic elements during differentiation of pluripotent stem cells.

The mechanisms underlying pluripotency and differentiation in embryonic and reprogrammed stem cells are unclear. In this work, we characterized the pluripotent state towards neural differentiated state through analysis of trace elements distribution using the Synchrotron Radiation X-ray Fluorescence Spectroscopy. Naive and neural-stimulated embryoid bodies (EB) derived from embryonic and induced pluripotent stem (ES and iPS) cells were irradiated with a spatial resolution of 20 µm to make elemental maps and qualitative chemical analyses. Results show that these embryo-like aggregates exhibit self-organization at the atomic level. Metallic elements content rises and consistent elemental polarization pattern of P and S in both mouse and human pluripotent stem cells were observed, indicating that neural differentiation and elemental polarization are strongly correlated.

Monte carlo simulation of bony heterogeneity effects on dose profile for small irradiation field in radiotherapy.

In the radiotherapy treatment planning of a lesion located in the head region with small field radiation beams, the heterogeneity corrections play an important role. In this work, we investigated the influence of a bony heterogeneity on dose profile inside a soft tissue phantom containing a bony material. PDD curves were obtained by simulation using the Monte Carlo code EGSnrc and employing Eclipse(R) treatment planning system algorithms (Batho, Modified Batho, Equivalent TAR and Anisotropic Analytic Algorithm) for a 15 MV photon beam and field sizes of 2x2 and 10x10 cm(2). The Equivalent TAR method exhibited better agreement with Monte Carlo simulations for the 2x2 cm(2) field size. The magnitude of the effect on PDD due to the bony heterogeneity for 1x1, 2x2 and 10x10 cm(2) field sizes increases to 10, 5 and 3%, respectively.