Search Results (7)

Multidrug resistance (MDR) represents a major obstacle to successful chemotherapy and, due to overlapping defense mechanisms, such as enhanced DNA repair and the evasion of apoptosis, can also be associated with radioresistance. In this study, we investigated whether MDR breast cancer cells (MCF-7/CMF) exhibit reduced susceptibility to radiation-induced DNA fragmentation compared to their non-resistant parental counterpart (MCF-7). Using a nucleosome-based ELISA, we quantified the chromatin fragmentation in MCF-7 and MCF-7/CMF cells following their exposure to four radiopharmaceuticals: [^99mTc]pertechnetate, [¹³¹I]NaI (sodium iodide), [¹²⁵I]NaI, and the DNA-incorporating compound [¹²⁵I]iododeoxyuridine ([¹²⁵I]IdU). Each radioactive preparation was assessed across a range of activity concentrations, using a two-way ANOVA. For [^99mTc]pertechnetate and [¹³¹I]NaI, significantly higher DNA fragmentation was observed in the sensitive cell line, whereas [¹²⁵I]NaI showed no significant difference between the two phenotypes. In contrast to the other radiopharmaceuticals, [¹²⁵I]IdU induced greater fragmentation in resistant cells. This finding was supported by the statistical analysis (a 63.7% increase) and visualized in the corresponding dose–response plots. These results highlight the critical role of the intranuclear enrichment of Auger emitters and support further development of radiopharmaceuticals in accordance with this principle. Our data suggest that radiotoxicity is governed not by linear energy transfer (LET) alone, but, fundamentally, by the spatial proximity of the radionuclide to the DNA. Targeting tumor cell DNA with precision radiotherapeutics may, therefore, offer a rational strategy to overcome MDR in breast cancer. Full article

^99mTc is a well-known radionuclide that is widely used and readily available for SPECT/CT (Single-Photon Emission Computed Tomography) diagnosis. However, commercial isotope carriers are not specific enough to tumours, rapidly clear from the bloodstream, and are not safe. To overcome these limitations, we suggest immunologically compatible recombinant proteins containing a combination of metal binding sites as ^99mTc chelators and several different tumour-specific ligands for early detection of tumours. E1b protein containing metal-binding centres and tumour-specific ligands targeting integrin α_vβ₃ and nucleolin, as well as a short Cys-rich sequence, was artificially constructed. It was produced in E. coli, purified by metal-chelate chromatography, and used to obtain a complex with ^99mTc. This was administered intravenously to healthy Balb/C mice at an activity dose of about 80 MBq per mouse, and the biodistribution was studied by SPECT/CT for 24 h. Free sodium ^99mTc-pertechnetate at the same dose was used as a reference. The selectivity of ^99mTc-E1b and the kinetics of isotope retention in tumours were then investigated in experiments in C57Bl/6 and Balb/C mice with subcutaneously transplanted lung carcinoma (LLC) or mammary adenocarcinoma (Ca755, EMT6, or 4T1). The radionuclide distribution ratio in tumour and adjacent normal tissue (T/N) steadily increased over 24 h, reaching 15.7 ± 4.2 for EMT6, 16.5 ± 3.8 for Ca755, 6.7 ± 4.2 for LLC, and 7.5 ± 3.1 for 4T1. Full article

(1) Background: Thyroid tissue ablation with radioactive iodine (RAI) has been successfully used in the treatment of differentiated thyroid cancers. However, as a side effect, RAI may induce salivary gland (SG) hypofunction, which has been alternatively managed with photobiomodulation therapy (PBMT). In our study, we assessed the effects of RAI on the SGs and further analyzed whether PBMT can minimize tissue damage. (2) Methods: Balb/c mice were allocated into three groups, as follows: RI, submitted to RAI orally; RIL, similar to RI, but with PBMT for SG hypofunction; and C, control group. The animals were euthanized on days 0, 10, and 90 after RAI. (3) Results: A decrease in tri-iodothyronine (T3) and thyroxine (T4) serum levels was observed both in the RI and RIL groups. In addition, a decrease in SG weight and morphological alterations were shown in the RI group throughout the experimental period, as well as a significant increase in total protein and peroxidase concentrations, and catalase activity. On day 90, the RI group presented less collagen and fewer sodium/iodine channels, with higher rates of cell apoptosis. Pertechnetate (Na^99mTcO₄) uptake was also affected in the RI group in all experimental times. Interestingly, although the RIL group also presented some alterations regarding these parameters, they were not statistically different from those of the C group on day 90. (4) Conclusions: Our results provide evidence that RAI induces harmful effects on the SGs, which can be successfully managed with PBMT. Full article

This study aimed to evaluate and compare the microleakage of composite resin restorations under a total-etch adhesive system applied with two different techniques, with and without cure. Cavities were made on the buccal surface of twenty-six intact teeth and subsequently restored with bulk-fill flow composite resin (SDR^®® flow+) and conventional resin (Spectra™ ST HV). Two experimental groups were created, one where the total-etch adhesive (Prime & Bond Active^®) was cured and another where the adhesive was not cured before placing the flowable resin. Two control groups were also created, negative and positive. After the restorations were finished the, teeth were submerged in a solution of sodium pertechnetate (^99mTcNaO4) for 3 h to evaluate the microleakage. The results showed more infiltration of radioisotopes characterized by the highest total count values of microleakage in group 1 (cured adhesive) and in the positive control. Group 2 (noncured adhesive) and the negative control showed lower values. We therefore considered that these groups were similar since their p-value was less than 0.05, with no statistically significant difference. Group 4 showed a statistically significant increase in relation to group 3 (p = 0.027). We concluded that the method of bulk-fill composite resins with noncured adhesive agents can have a positive effect on the longevity of bond strengths, with reduced microleakage. Full article

Congenital iodide transport defect is an uncommon autosomal recessive disorder caused by loss-of-function variants in the sodium iodide symporter (NIS)-coding SLC5A5 gene and leading to dyshormonogenic congenital hypothyroidism. Here, we conducted a targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients suspected of having a congenital iodide transport defect based on the absence of ^99mTc-pertechnetate accumulation in a eutopic thyroid gland. Although, unexpectedly, we could not detect pathogenic SLC5A5 gene variants, we identified two novel compound heterozygous TG gene variants (p.Q29* and c.177-2A>C), three novel heterozygous TG gene variants (p.F1542Vfs*20, p.Y2563C, and p.S523P), and a novel heterozygous DUOX2 gene variant (p.E1496Dfs*51). Splicing minigene reporter-based in vitro assays revealed that the variant c.177-2A>C affected normal TG pre-mRNA splicing, leading to the frameshift variant p.T59Sfs*17. The frameshift TG variants p.T59Sfs*17 and p.F1542Vfs*20, but not the DUOX2 variant p.E1496Dfs*51, were predicted to undergo nonsense-mediated decay. Moreover, functional in vitro expression assays revealed that the variant p.Y2563C reduced the secretion of the TG protein. Our investigation revealed unexpected findings regarding the genetics of congenital iodide transport defects, supporting the existence of yet to be discovered mechanisms involved in thyroid hormonogenesis. Full article

The aim of this study was to evaluate and compare the sealing ability of two calcium silicate-based sealers (TotalFill BC RRM Fast Set Putty and White ProRoot MTA) when used as apical plugs in immature teeth through nuclear medicine. Single-rooted extracted teeth (n = 34) had their crowns and root tip sectioned to obtain 14 mm long root segments to simulate an in vitro apexification model. Were created two experimental groups, namely MTA (n = 12) and BC (n = 12), and two control groups, PG (positive group, n = 5) and NG (negative group, n = 5). On the 4th day after placing the respective apical plug, the apical portions of the teeth were submerged in a solution of sodium pertechnetate (^99mTcNaO₄) for 3 h. Statistical analysis showed a significant difference between the MTA group and the controls (p < 0.05). The BC group had a significant difference regarding the negative control (p < 0.001) but showed no statistical significance regarding the positive control (p = 0.168). There was a statistically significant difference (p = 0.009) between the BC group (7335.8 ± 2755.5) and the MTA group (4059.1 ± 1231.1), where the last showed less infiltration. Within the limitations of this study, White ProRoot MTA had a significantly better sealing ability than TotalFill BC RRM Fast Set Putty. Full article

In addition to its nutritional value, Paullinia cupana (guarana) is commonly used in traditional medicine, known for its stimulant and medicinal properties. This investigation evaluated the effects of a guarana extract in combination with whole-body vibration (WBV) exercises on Wistar rats. Rats (male, n = 20) were divided into the following four groups: control (CON), treated with guarana (GUA), submitted to 50 Hz of WBV (WBV-E), treated with guarana and submitted to 50 Hz of WBV (GUA + WBV-E), daily for 6-weeks. Guarana altered (p < 0.05) the uptake of the radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in muscle. Additionally, it modified the stool consistency, and in combination with WBV decreased the food intake without modifying body mass. The levels of calcium increased in the groups submitted to WBV exercises (WBV-E and GUA + WBV-E) as compared with the GUA group. The outcomes provide additional evidence of the biological effects of guarana separately or in combination with WBV and supports the use of guarana as a functional food. Full article