Translational Aspects of Nuclear Factor-Kappa B and Its Modulation by Thalidomide on Early and Late Radiation Sequelae in Urinary Bladder Dysfunction

Purpose: This preclinical study aimed to investigate the role of nuclear factor (NF)-κB in early and late radiogenic sequelae of urinary bladder dysfunction in mice. Thalidomide was applied either during the early or late response phase to determine potential effects of NF-κB inhibition on functional bladder impairment. Methods and Materials: After pelvic irradiation on day 0, female C3H/Neu mice were observed over a period of 360 days and radiation response was evaluated for alterations in bladder functionality and NF-κB activation. Functionality was determined in graded dose experiments (14-24 Gy) and assessed by micturition frequency analysis and transurethral cystotonometry to reveal alterations in voiding and volume. The induction of the NF-κB proteins p50 and p65 was evaluated by immunohistochemistry in response to a single dose of 23 Gy (ED90). Thalidomide (100 mg/kg/d) was applied intraperitoneally in 3 treatment groups: daily from day 1 to 15, daily from day 16 to 30, and in 2-day-intervals from day 150 to 180. Results: Immunohistochemical analysis showed a biphasic activation of p50 and p65 during the early radiation cystitis phase (day 1-30). After a transient decrease, p50, but not p65, was reactivated permanently leading to increased levels, which suggests an occurrence of chronic inflammation correlated with functional impairment. Both early thalidomide treatments reduced NF-κB activation and shifted the ED50 value for early radiation cystitis and late radiation sequelae to higher doses. Conclusions: These data clearly demonstrate the involvement of NF-κB signaling in the pathogenesis of radiation-induced urinary bladder dysfunction. Additionally, this study emphasizes that biological targeting of early radiogenic processes has enormous effect on chronic symptoms. The late administration of thalidomide showed no significant effect on functionality. © 2020 The Author(s

Heparin treatment mitigates radiation-induced oral mucositis in mice by interplaying with repopulation processes

Purpose To investigate the mechanistic background of the muco-protective effect of systemic heparin treatment on the development of radiation-induced oral mucositis in mice. Materials and methods Fractionated irradiation was given to the snouts of male C3H/Neu mice over 2 weeks (10 3 Gy), either alone or in combination with daily subcutaneous application of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively). Over this course of 14 days, groups of mice (n = 3) were sacrificed every second day, their tongues excised and processed for histological analysis. The epithelial radiation response with and without heparin treatment was evaluated in terms of tissue morphology, proliferation and expression of cell contact molecules. Results Systemic treatment with heparins significantly reduced the cellular effects of irradiation to the oral epithelium. Heparin treated animals showed significantly higher total epithelial cell numbers and thickness throughout the study course. Bromodeoxyuridine (BrdU) incorporation analyses revealed that markedly more epithelial cells retained their proliferative capacity in the beginning of the first treatment week, but the proliferation of the mucosa was not stimulated during the rest of the study course. The expression of the adherens junction protein catenin was slightly elevated in heparin treated animals, on day 2 the increase was statistically significant. The expression of ecadherin and occludin was mostly unaffected by the concomitant heparin treatment. Conclusion The findings of this study indicate an interplay of additional heparin treatment with the repopulation processes, leading to an earlier onset of this adaptive radiation response in oral mucosa. Importantly, we could demonstrate that the protective potential of heparin did not rely on stimulation of normal tissue proliferation. Since both heparin preparations are already approved for clinical use, they are considered as promising candidates for future clinical studies.(VLID)366404

Data from: A validated Tumor Control Probability model based on a meta-analysis of low, intermediate, and high-risk prostate cancer patients treated by photon, proton, or carbon-ion radiotherapy

This dataset supports the publication by Walsh et al, entitled "A validated Tumor Control Probability model based on a meta-analysis of low, intermediate, and high-risk prostate cancer patients treated by photon, proton, or carbon-ion radiotherapy"

Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer

Purpose: Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. Methods: 28 PCa patients (54–80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. Results: The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. Conclusions: The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT