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Cell­extracellular matrix (ECM) interactions are thought to mediate drug and radiation resistance. Dependence of cell survival, β1-integrin expression and cell cycling on the ECM proteins and &betal;1-integrin ligands fibronectin (FN) and laminin (LA) were examined in malignant and normal cells exposed to the cytotoxic drug Ukrain plus/minus irradiation. FN and LA reduced the cytotoxic effect of single Ukrain treatment compared with polystyrene and BSA. FN and LA also abolished Ukrain-dependent radiosensitization in A549 cells and decreased the radiosensitivity of MDA231 and HSF1 cells. Single Ukrain exposure on polystyrene significantly reduced β1-integrin expression and promoted G2-phase accumulation of A549 cells. In contrast, Ukrain-treated MDA231 and HSF1 cells showed elevated β1-integrin expression and no Ukrain-specific cell cycle effect. Under Ukrain-radiation exposure, irradiation, FN or LA abolished Ukrain-mediated reduction of β1-integrin expression and G2-phase accumulation in A549 cells, whereas in MDA231 cells and fibroblasts β1-integrin expression and cell cycle distribution were stabilized. Cell adhesion to FN or LA was significantly impaired (A549) or improved (MDA231, HSF1) upon Ukrain treatment. The data corroborate the findings of other groups that cell adhesion-mediated resistance to either single or combined drug and radiation exposure is tightly correlated to specific ECM proteins. By demonstrating a strong modulatory impact of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, these findings are also highly important for the assessment of drug and radiation effects within in vitro cytotoxicity studies. The data give the first mechanistic insights into specific FN- and LA-modulated cellular resistance mechanisms as well as into the important role for β1-integrins using the unique cytotoxic and radiosensitivity-modifying drug Ukrain. [ABSTRACT FROM AUTHOR]

Aim: Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals.Material and Method: A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS).Results: Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected.Conclusions: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization. [ABSTRACT FROM AUTHOR]

Background and Objective: Our aim was to develop a tool using readily available clinical parameters to predict the probability of poor urinary function following low-dose-rate brachytherapy (LDR-BT) for localized prostate cancer., Methods: Data from the multicentre, prospective Swiss LDR-BT cohort were analyzed for men treated with LDR-BT. Inclusion criteria were minimum follow-up of 3 yr or postoperative treatment with transurethral resection of the prostate (TURP). A total of 914 men were analyzed, with complete data available for 607 men. Pre-interventional variables assessed were International Prostate Symptom Score (IPSS), prostate volume (PV), maximum urinary flow rate, prostate-specific antigen, postvoid residual urine volume, and age. The primary outcome was poor urinary function after LDR-BT, defined as an IPSS-Quality of Life score >3 ("mostly dissatisfied" or worse) at 3 yr or the occurrence of TURP during follow-up. Associations were evaluated using univariable and multivariable logistic regression. Receiver operating characteristic curve analysis was also performed., Key Findings and Limitations: Poor urinary function outcomes were observed in 46 patients (5.0%). Significant predictors included pre-interventional IPSS (adjusted odds ratio [aOR] per point 1.18; p  < 0.001) and PV (aOR per ml, 1.04; p  = 0.004). Limitations of the study include potential selection bias and the absence of external validation., Conclusions and Clinical Implications: Pre-interventional IPSS and PV were significant predictors of poor urinary function after LDR-BT for prostate cancer. A risk calculator based on these parameters was developed to assist individualized treatment planning. Further studies are needed to validate these findings before they can be applied in routine clinical practice., Patient Summary: We created a tool to predict the likelihood of urinary problems after a type of radiotherapy called brachytherapy for prostate cancer. The size of the prostate and urinary symptoms before treatment were associated with poor urinary function after treatment. This tool could help doctors and patients in making informed decisions about treatment for prostate cancer., (© 2024 The Authors.)

Nanoparticle radioenhancement offers a promising strategy for augmenting radiotherapy by locally increasing radiation damage to tumor tissue. While past research has predominantly focused on nanomaterials with high atomic numbers, such as Au and HfO 2 , recent work has revealed that their radioenhancement efficacy decreases considerably when using clinically relevant megavoltage X-rays as opposed to the orthovoltage X-rays typically employed in research settings. Here, radiocatalytically active Ti-based nanomaterials for clinical X-ray therapy settings are designed. A range of candidate materials, including TiO 2 (optionally decorated with Ag or Pt nanoseeds), Ti-containing metal-organic frameworks (MOFs), and 2D Ti-based carbides known as Ti 3 C 2 T x MXenes, is investigated. It is demonstrated that these titanium-based candidates remain consistently performant across a wide energy spectrum, from orthovoltage to megavoltage. This sustained performance is attributed to the catalytic generation of reactive oxygen species, moving beyond the simple physical dose enhancements associated with photoelectric effects. Beyond titania, emergent materials like titanium-based MOFs and MXenes exhibit encouraging results, achieving dose-enhancement factors of up to three in human soft tissue sarcoma cells. Notably, these enhancements are absent in healthy human fibroblast cells under similar conditions of particle uptake, underscoring the selective impact of titanium-based materials in augmenting radiotherapy across the clinically relevant spectral range., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO 2 , TiO 2 , WO 3 and HfO 2 ), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO 2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO 2 nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO 2 , leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy., (© 2022. The Author(s).)