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Among the tumors with the highest lethality, gliomas are primary brain tumors associated with common recurrence inclined to metastasize along the neuraxis and occasionally out of the central nervous system. Even though metastasis is the main responsible for death in oncological patients, few dedicated treatments are approved. Therefore, the establishment of effective anti-metastasis agents is the final frontier in cancer research. Interestingly, some copper complexes have demonstrated promising efficacy as antimetastatic agents, but they may cause off-site effects such as the alteration of copper homeostasis in healthy tissues. Thus, the incorporation of copper-based antimetastatic agents in rationally designed nano-architectures can increase the treatment localization reducing the side effects. Here, copper complex loaded hybrid nano-architectures (CuLNAs) are presented and employed to assess the impact of an intracellular copper source on glioma cell invasiveness. The novel CuLNAs are fully characterized and exploited for cell migration modulation in a glioma cell line. The results demonstrate that CuLNAs significantly reduce cell migration without impairing cell proliferation compared to standard gold and copper NAs. A concomitant antimigratory-like regulation of the epithelial-to-mesenchymal transition genes confirmed these results, as the gene encoding for the epithelial protein E-cadherin was upregulated and the other explored mesenchymal genes were downregulated. These findings, together with the intrinsic behaviors of NAs, demonstrate that the inclusion of metal complexes in the nano-architectures is a promising approach for the composition of a family of agents with antimetastatic activity., Competing Interests: Declaration of Competing Interest The Authors declare no competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs)., Methods and Materials: FNTDs were exposed behind solid water to proton and helium ( 4 He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LET F and LET D , respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations., Results: For protons, average relative differences between measurements and simulations were 6% and 19% for LET F and LET D , respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LET D as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy., Conclusions: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Minibeam radiation therapy (MBRT) is an innovative dose delivery method with the potential to spare normal tissue while achieving similar tumor control as conventional radiotherapy. However, it is difficult to use a single dose parameter, such as mean dose, to compare different patterns of MBRT due to the spatially fractionated radiation. Also, the mechanism leading to the biological effects is still unknown., Purpose: This study aims to demonstrate that the hydrogen peroxide (H 2 O 2 ) distribution could serve as a surrogate of dose distribution when comparing different patterns of MBRT., Methods: A free diffusion model (FDM) for H 2 O 2 developed with Fick's second law was compared with a previously published model based on Monte Carlo & convolution method. Since cells form separate compartments that can eliminate H 2 O 2 radicals diffusing inside the cell, a term describing the elimination was introduced into the equation. The FDM and the diffusion model considering removal (DMCR) were compared by simulating various dose rate irradiation schemes and uniform irradiation. Finally, the DMCR was compared with previous microbeam and minibeam animal experiments., Results: Compared with a previous Monte Carlo & Convolution method, this analytical method provides more accurate results. Furthermore, the new model shows H 2 O 2 concentration distribution instead of the time to achieve a certain H 2 O 2 uniformity. The comparison between FDM and DMCR showed that H 2 O 2 distribution from FDM varied with dose rate irradiation, while DMCR had consistent results. For uniform irradiation, FDM resulted in a Gaussian distribution, while the H 2 O 2 distribution from DMCR was close to the dose distribution. The animal studies' evaluation showed a correlation between the H 2 O 2 concentration in the valley region and treatment outcomes., Conclusion: DMCR is a more realistic model for H 2 O 2 simulation than the FDM. In addition, the H 2 O 2 distribution can be a good surrogate of dose distribution when the minibeam effect could be observed., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The influence of different average and bunch dose rates in electron beams on the FLASH effect was investigated. The present study measures O 2 content in water at different beam pulse patterns and finds strong correlation with biological data, strengthening the hypothesis of radical-related mechanisms as a reason for the FLASH effect., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nephron sparing surgery (NSS) is increasingly utilized to treat patients with bilateral Wilms tumor. We present a case of NSS planning using a three-dimensional computerized and printed model of both kidneys with anatomical structures of interest (parenchyma, renal pelvis, major calyx, renal artery, renal vein, and tumor). This model allowed a better understanding of the anatomic relation between the tumor and the normal kidney on each side, improving the surgical planning and the preoperative discussion with the patient's family., (© 2017 Wiley Periodicals, Inc.)